{ "name": "PeptideOS", "license": "CC-BY-4.0", "generated": "2026-10-14", "publisher": "Open Source Medicine Foundation", "tiers": { "E1": "Multiple adequately powered RCTs, consistent", "E2": "At least one adequately powered RCT", "E3": "Small, underpowered or conflicting RCTs", "E4": "Uncontrolled or non-randomised human trials", "E5": "Case reports and case series only", "E6": "Animal models only", "E7": "In vitro only", "E8": "No published evidence of efficacy in any model" }, "safety_grades": { "S1": "Large long-term human exposure (post-marketing surveillance)", "S2": "Substantial controlled-trial safety data", "S3": "Limited human safety data", "S4": "Minimal human exposure data", "S5": "No human safety data" }, "classes": { "A": "Approved", "B": "Investigational", "C": "Gray market" }, "compounds": [ { "slug": "afamelanotide", "names": { "inn": "afamelanotide", "common": [ "Afamelanotide", "Melanotan-1", "MT-1", "[Nle4, D-Phe7]-alpha-MSH" ], "codes": [ "CUV1647" ], "brands": [ "Scenesse" ], "cas": null }, "sequence": null, "sequence_note": "Linear tridecapeptide analogue of alpha-MSH: Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2, per the US prescribing information. Contains norleucine and a D-amino acid, so no plain one-letter sequence is given.", "class_by_jurisdiction": { "US": "A", "EU": "A", "UK": "A", "CA": "A", "AU": "A", "JP": null, "CN": null }, "what_it_is": "A synthetic analogue of alpha-melanocyte-stimulating hormone that binds mainly to the melanocortin-1 receptor and increases eumelanin in the skin. It is approved as a controlled-release subcutaneous implant (Scenesse) for adults with erythropoietic protoporphyria (EPP), a rare inherited condition causing painful reactions to light, in the US, EU, UK, Canada and Australia. The same molecule (Melanotan-1) is also sold as unapproved powder for cosmetic tanning; that material is not the approved product.", "evidence": [ { "indication": "Phototoxicity in erythropoietic protoporphyria (adults)", "tier": "E1", "human_rcts": 2, "human_trials_any": null, "summary": "Two multicentre, double-blind, placebo-controlled RCTs (74 patients in the EU, 94 in the US) found longer pain-free direct sunlight exposure with afamelanotide (US median 69.4 versus 40.8 hours over 6 months; EU median 6.0 versus 0.8 hours over 9 months) and improved quality of life. An observational study of 115 patients treated for up to 8 years at two centres reported sustained use and only minor adverse events. The EU authorisation is under exceptional circumstances because comprehensive data could not be obtained.", "citations": [ { "doi": "10.1056/nejmoa1411481", "title": "Afamelanotide for Erythropoietic Protoporphyria", "year": 2015, "finding": "Two RCTs: longer pain-free sunlight exposure and fewer phototoxic reactions (EU trial) than placebo in EPP" }, { "doi": "10.1111/bjd.13598", "title": "Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria", "year": 2015, "finding": "Sustained use and improved EPP quality-of-life scores over up to 8 years; mainly minor adverse events such as nausea" } ], "trials_query": "afamelanotide" }, { "indication": "Nonsegmental vitiligo (with narrowband UV-B phototherapy)", "tier": "E3", "human_rcts": 1, "human_trials_any": null, "summary": "One small randomised multicentre trial (55 patients, skin phototypes III-VI) found faster and greater repigmentation with afamelanotide plus narrowband UV-B than with UV-B alone. A larger phase 3 trial is registered and active but had not reported on the retrieval date. Vitiligo is not an approved indication in any jurisdiction checked.", "citations": [ { "doi": "10.1001/jamadermatol.2014.1875", "title": "Afamelanotide and Narrowband UV-B Phototherapy for the Treatment of Vitiligo", "year": 2015, "finding": "Greater and earlier repigmentation with combination therapy than narrowband UV-B alone in a 55-patient RCT" } ], "trials_query": "afamelanotide" }, { "indication": "Cosmetic tanning in healthy people (gray-market 'Melanotan-1' claim)", "tier": "E3", "human_rcts": 2, "human_trials_any": 3, "summary": "Three small phase 1 studies in healthy volunteers (two of them randomising 8 subjects each, one open-label with 12) reported skin darkening and enhanced tanning with sunlight or UV-B. These were safety studies of short duration. There is no evidence that induced tanning reduces skin cancer or sunburn in real-world use, and no data on gray-market material.", "citations": [ { "doi": "10.1001/archderm.140.7.827", "title": "Effects of a Superpotent Melanotropic Peptide in Combination With Solar UV Radiation on Tanning of the Skin in Human Volunteers", "year": 2004, "finding": "Enhanced tanning with sunlight or UV-B in small phase 1 studies of healthy volunteers; nausea and transient facial flushing reported" } ], "trials_query": "afamelanotide" } ], "safety": { "grade": "S2", "no_data_statement": true, "known_signals": [ { "signal": "Serious hypersensitivity reactions, including anaphylaxis", "evidence": "US prescribing information Warnings and Precautions 5.1.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210797s007lbl.pdf", "title": "SCENESSE (afamelanotide) implant, for subcutaneous use" } }, { "signal": "Darkening of pre-existing naevi and ephelides", "evidence": "US prescribing information Warnings and Precautions 5.2 (skin monitoring); periodic full-body skin examination is recommended in the label.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210797s007lbl.pdf", "title": "SCENESSE (afamelanotide) implant, for subcutaneous use" } }, { "signal": "Nausea", "evidence": "Most frequently recorded adverse event attributed to afamelanotide in long-term observational use.", "citation": { "doi": "10.1111/bjd.13598", "title": "Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "approved", "detail": "NDA 210797 (Scenesse implant), approved 8 October 2019 (priority review, orphan); applicant Clinuvel Inc. Latest label supplement 12 August 2024.", "source_url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210797s007lbl.pdf", "source_title": "SCENESSE prescribing information (FDA, revised 08/2024)", "quote": "SCENESSE is a melanocortin 1 receptor (MC1-R) agonist indicated to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP).", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "approved", "detail": "Centrally authorised 22 December 2014 under exceptional circumstances; indication: prevention of phototoxicity in adult patients with EPP. Under additional monitoring.", "source_url": "https://www.ema.europa.eu/en/medicines/human/EPAR/scenesse", "source_title": "Scenesse EPAR (EMA)", "quote": "The European Commission granted a marketing authorisation valid throughout the European Union for Scenesse on 22 December 2014.", "retrieved": "2026-10-10" }, { "jurisdiction": "UK", "status": "approved", "detail": "Great Britain marketing authorisation PLGB 30619/0002; SmPC retrieved from the MHRA products database (document dated 12 June 2026).", "source_url": "https://mhraproducts4853.blob.core.windows.net/docs/9478ca37862d6bdd2ad69f88c442cf74aa32e0d3", "source_title": "SCENESSE Summary of Product Characteristics (MHRA products database)", "quote": "SCENESSE is indicated for prevention of phototoxicity in adult patients with erythropoietic protoporphyria (EPP).", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "approved", "detail": "Drug Product Database: SCENESSE, DIN 02569825, Clinuvel Inc.; status Approved on 9 July 2026, with no market date recorded on the retrieval date (approved, not yet recorded as marketed).", "source_url": "https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=107203", "source_title": "Health Canada Drug Product Database: SCENESSE", "quote": "Current status: Approved Current status date: 2026-07-09", "retrieved": "2026-10-10" }, { "jurisdiction": "AU", "status": "approved", "detail": "ARTG 327947, sponsor Clinuvel Pharmaceuticals Ltd, ARTG start date 18 November 2020, status Active; medicine under additional monitoring. Afamelanotide is also a Schedule 4 (prescription-only) substance in the Poisons Standard.", "source_url": "https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=327947&agid=(PrintDetailsPublic)&actionid=1", "source_title": "TGA ARTG Public Summary 327947: SCENESSE afamelanotide (as acetate) implant vial", "quote": "SCENESSE is indicated for prevention of phototoxicity in adult patients with erythropoietic protoporphyria (EPP)", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "not_prohibited", "wada_class": null, "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "trials": [ { "nct": "NCT01605136", "title": "Phase III Confirmatory Study in Erythropoietic Protoporphyria", "phase": "3", "status": "Completed" }, { "nct": "NCT00979745", "title": "Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)", "phase": "3", "status": "Completed" }, { "nct": "NCT01097044", "title": "Phase II Confirmatory Study in Erythropoietic Protoporphyria (EPP)", "phase": "2", "status": "Completed" }, { "nct": "NCT06109649", "title": "A Study to Compare the Efficacy and Safety of SCENESSE and Narrow-Band Ultraviolet (NB-UVB) Light Versus NB-UVB Light Alone in Patients With Vitiligo", "phase": "3", "status": "Active, not recruiting" } ], "unknowns": [ "Efficacy and safety in children and adolescents with EPP are not established", "Long-term melanocytic effects (naevus changes, melanoma risk) beyond observational follow-up of about a hundred patients are not characterised", "No adequately powered RCT in vitiligo has reported", "No data on identity, purity or sterility of gray-market 'Melanotan-1' powders, or on their safety outside the approved implant formulation" ], "mechanism": "Afamelanotide is an alpha-MSH analogue that binds predominantly to the melanocortin-1 receptor and increases eumelanin production in the skin independently of UV exposure.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "aod-9604", "names": { "inn": null, "common": [ "AOD-9604", "AOD9604", "Tyr-hGH(177-191)" ], "codes": [ "AOD9604" ], "brands": [], "cas": null }, "sequence": null, "sequence_note": "Described by its developers as Tyr-hGH(177-191): a tyrosine residue followed by residues 177-191 of human growth hormone. The exact residue sequence and any disulfide bond were not verified from a primary source for this record, so no one-letter sequence is given.", "class_by_jurisdiction": { "US": "C", "EU": null, "UK": null, "CA": null, "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic peptide fragment from the end of human growth hormone, developed by the Australian company Metabolic Pharmaceuticals as an oral anti-obesity drug. Six placebo-controlled trials were run in the early 2000s; development stopped in 2007 after a large 24-week trial reportedly found no significant weight loss versus placebo. It is not an approved medicine, and is sold on the gray market with fat-loss and joint claims.", "evidence": [ { "indication": "Weight loss and fat reduction in obesity", "tier": "E3", "human_rcts": null, "human_trials_any": null, "summary": "The developer ran six randomised, double-blind, placebo-controlled trials in about 900 adults, mostly with obesity, by mouth or single intravenous doses. Their efficacy results were never published as primary peer-reviewed reports; the published summary covers safety only. A review states that a 12-week trial showed modestly greater weight loss than placebo, but that development ended after a 24-week trial in 536 people failed to show significant weight loss. The evidence is therefore conflicting and incompletely reported. No trial of injected AOD-9604 for weight loss was identified. Rodent studies reported reduced weight gain and increased fat breakdown.", "citations": [ { "doi": "10.4021/jem157w", "title": "Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans", "year": 2013, "finding": "Sponsor-funded safety summary of six randomised placebo-controlled trials; reports safety outcomes, not weight-loss results" }, { "doi": "10.2174/157340313805076322", "title": "Obesity pharmacotherapy: current perspectives and future directions", "year": 2013, "finding": "Review reporting that development stopped in 2007 after a 24-week trial in 536 participants did not show significant weight loss" }, { "doi": "10.1038/sj.ijo.0801740", "title": "Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment", "year": 2001, "finding": "Reduced body weight gain and increased fat oxidation in obese mice, without the blood-glucose effects of full growth hormone" } ], "trials_query": "AOD9604" }, { "indication": "Joint cartilage and osteoarthritis", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "Joint claims rest on a rabbit osteoarthritis model in which AOD-9604 was injected into the knee with or without hyaluronic acid. No human study of osteoarthritis, cartilage or joint injury has been published.", "citations": [ { "pmid": 26275694, "title": "Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model.", "year": 2015, "finding": "Intra-articular injection studied in a rabbit model of osteoarthritis" } ], "trials_query": "AOD9604" } ], "safety": { "grade": "S2", "no_data_statement": false, "known_signals": [ { "signal": "Serious adverse events of unclear causality (FDA)", "evidence": "FDA states that it has identified serious adverse events that may be associated with AOD-9604, though causality is not clear, and that it has no, or only limited, safety information. The sponsor-funded trial summary reports no AOD-9604-related withdrawals or serious adverse events and more gastrointestinal events at the highest oral dose.", "citation": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "No FDA-approved product. AOD-9604 was formerly in 503A Category 2 and now appears on FDA's list of substances nominated but withdrawn, with FDA's stated risks. Page content current as of 22 April 2026. It does not appear in any category of FDA's 503A nominations list updated 14 May 2026.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "quote": "Compounded drugs containing AOD-9604 may pose significant risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization.", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S2.2.3", "detail": "Named as a growth hormone fragment in class S2.2.3, prohibited at all times, on the 2026 Prohibited List.", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Growth hormone (GH), its analogues and fragments including, but not limited to: growth hormone analogues, e.g. lonapegsomatropin, somapacitan and somatrogon growth hormone fragments, e.g. AOD-9604 and hGH 176-191" }, "unknowns": [ "Full weight-loss results of the six developer trials, including the failed 24-week trial, have never been published in a peer-reviewed journal", "The human trials used oral or single intravenous doses; no published human data cover repeated subcutaneous injection", "No trial lasted longer than 24 weeks, so long-term human safety is unknown", "FDA's reported serious adverse events have not been described publicly in enough detail to judge causality", "Identity and purity of gray-market products are unverified; a 2014 Belgian analysis of seized products was a case report only", "Regulatory status outside the US was not verified from regulator sources for this record" ], "mechanism": "AOD-9604 does not bind the growth hormone receptor in cell assays. In obese mice it increased fat oxidation and markers of fat breakdown without the blood-glucose effects of full growth hormone; its molecular target is not established.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "bpc-157", "names": { "inn": null, "common": [ "BPC-157", "BPC 157", "Body Protection Compound-157", "Bepecin", "Stable gastric pentadecapeptide BPC 157" ], "codes": [ "PL 14736", "PL-10", "PLD-116" ], "brands": [], "cas": "137525-51-0" }, "sequence": "GEPPPGKPADDAGLV", "sequence_note": "Free base; CAS number as given for BPC-157 (free base) in FDA's July 2026 briefing document. BPC-157 acetate is a distinct salt form. Described by its originators as a fragment of a protein from gastric juice.", "class_by_jurisdiction": { "US": "C", "EU": null, "UK": null, "CA": null, "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic 15-amino-acid peptide first described by a research group in Zagreb in 1993. It is sold widely on the gray market and through some clinics with claims of tendon, ligament, muscle and gut \"healing\". FDA's July 2026 briefing document states that no product containing it is approved in any country. Almost all published efficacy data are from rodent studies, most from a single research group; human data are limited to small uncontrolled reports and one trial reported only as a conference abstract.", "evidence": [ { "indication": "Tendon, ligament, muscle and joint injury", "tier": "E5", "human_rcts": 0, "human_trials_any": 0, "summary": "The musculoskeletal claims rest on rat studies of cut or detached tendons, ligaments and muscles, nearly all from one Zagreb group. The only human report is a retrospective chart review with telephone follow-up of 16 clinic patients given intra-articular injections for knee pain of mixed causes, some with a second peptide; it had no control group and no standardised outcome measure. No randomised or prospective controlled human study has been published. FDA's 2026 briefing document states that it did not identify clinical studies of BPC-157 for tendonitis. A placebo-controlled hamstring-strain trial and a rotator-cuff pilot trial are registered but have not reported.", "citations": [ { "pmid": 34324435, "title": "Intra-Articular Injection of BPC 157 for Multiple Types of Knee Pain.", "year": 2021, "finding": "Retrospective chart review with telephone survey of 16 clinic patients with knee pain; no control group, no validated outcome measures" }, { "doi": "10.1016/S0736-0266(03)00110-4", "title": "Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth", "year": 2003, "finding": "Improved biomechanical, functional and histological measures after Achilles tendon transection in rats" }, { "doi": "10.1002/jor.21107", "title": "Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat", "year": 2010, "finding": "Improved functional, biomechanical and histological measures after medial collateral ligament transection in rats" } ], "trials_query": "BPC-157" }, { "indication": "Ulcerative colitis and inflammatory bowel disease", "tier": "E3", "human_rcts": 1, "human_trials_any": 1, "summary": "An enema formulation (PL 14736) was developed by the Croatian company Pliva for inflammatory bowel disease in the early 2000s. FDA's 2026 briefing document identified a single randomised, double-blind, placebo-controlled trial in 53 people with mild-to-moderate ulcerative colitis, reported only as a 2005 conference abstract; the between-group difference in its disease-activity score was not statistically significant. FDA concluded that there is a lack of evidence to support effectiveness in ulcerative colitis. Other data are from rat models. The developers' review cited here describes the clinical programme but reports no trial results.", "citations": [ { "doi": "10.1007/s10787-006-1531-7", "title": "Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response", "year": 2006, "finding": "Review by the originating group describing the inflammatory bowel disease clinical programme and rat gastric-lesion experiments; no human efficacy results reported" }, { "doi": "10.3748/wjg.v23.i48.8465", "title": "Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights", "year": 2017, "finding": "Reduced visible mucosal damage and oxidative-stress markers in a rat model of ischaemic colitis" } ], "trials_query": "BPC-157" }, { "indication": "Stomach and gut lining injury (ulcers, NSAID damage, 'leaky gut')", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "Many rat experiments report fewer stomach and intestinal lesions when BPC-157 is given alongside alcohol, anti-inflammatory drugs or other injuries. No human study of gastric ulcers, drug-induced gut injury, intestinal permeability or general digestive symptoms has been published.", "citations": [ { "doi": "10.3748/wjg.v23.i29.5304", "title": "Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME", "year": 2017, "finding": "Fewer gastric, liver and brain lesions after high-dose celecoxib in rats given BPC-157" } ], "trials_query": "BPC-157" }, { "indication": "Interstitial cystitis (bladder pain syndrome)", "tier": "E4", "human_rcts": 0, "human_trials_any": 1, "summary": "One uncontrolled single-clinic pilot study injected compounded BPC-157 into the bladder wall of 12 women whose interstitial cystitis had not responded to pentosan polysulfate, and reported symptom resolution on a global response questionnaire. There was no control group, no blinding and no objective outcome measure, so placebo response and natural fluctuation cannot be excluded.", "citations": [ { "pmid": 39325560, "title": "Effect of BPC-157 on Symptoms in Patients with Interstitial Cystitis: A Pilot Study.", "year": 2024, "finding": "Uncontrolled pilot study in 12 women; self-rated symptom improvement reported, no comparator" } ], "trials_query": "BPC-157" } ], "safety": { "grade": "S4", "no_data_statement": true, "known_signals": [ { "signal": "Adverse event reports with injected products (FDA FAERS)", "evidence": "FDA's 2026 briefing document summarises three FAERS reports, all with injectable BPC-157: injection-site redness and swelling, shortness of breath leading to an emergency visit, and diffuse skin and gum hyperpigmentation that recurred on rechallenge with a 'research purposes only' product that also contained TB-500. FDA states that causality cannot be established from these reports.", "citation": { "url": "https://www.fda.gov/media/193343/download", "title": "FDA Evaluation of BPC-157-Related Bulk Drug Substances" } }, { "signal": "Clotting and liver findings in animal toxicity studies", "evidence": "FDA reports that 28-day intramuscular toxicity studies in rats and dogs showed altered clotting times (aPTT) and liver-associated changes (raised ALT, glucose and triglycerides); longer studies and carcinogenicity studies were not available.", "citation": { "url": "https://www.fda.gov/media/193343/download", "title": "FDA Evaluation of BPC-157-Related Bulk Drug Substances" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "No FDA-approved product. BPC-157 was formerly in 503A Category 2 (substances raising significant safety risks); the nominations were withdrawn and it now appears on FDA's list of substances nominated but withdrawn. FDA re-evaluated BPC-157 (free base) and BPC-157 acetate on its own initiative, for ulcerative colitis only, for the Pharmacy Compounding Advisory Committee meeting of 23 July 2026. FDA's briefing document recommended against adding either form to the 503A bulks list. The committee's vote and any final FDA decision were not verified from an FDA source for this record.", "source_url": "https://www.fda.gov/media/193343/download", "source_title": "July 23-24, 2026, Meeting of the Pharmacy Compounding Advisory Committee – FDA Briefing Document for BPC-157-Related Bulk Drug Substances (BPC-157 (free base) and BPC-157 acetate)", "quote": "After considering the information currently available, a balancing of the criteria weighs against BPC-157 (free base) and BPC-157 acetate being placed on that list", "retrieved": "2026-10-10" }, { "jurisdiction": "US", "status": "unapproved", "detail": "FDA's page on bulk drug substances that may present significant safety risks lists BPC-157 under 'Bulk drug substances nominated but withdrawn' (substances previously in Category 2) and gives FDA's stated risks. Page content current as of 22 April 2026.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "quote": "Compounded drugs containing BPC-157 may pose risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and active pharmaceutical ingredient (API) characterization.", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S0", "detail": "Named in class S0 (non-approved substances), prohibited at all times, on the 2026 Prohibited List.", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "This class covers many different substances including but not limited to BPC-157, 2,4-dinitrophenol (DNP), ryanodine receptor-1-calstabin complex stabilizers" }, "trials": [ { "nct": "NCT02637284", "title": "PCO-02 - Safety and Pharmacokinetics Trial", "phase": "1", "status": "Unknown" }, { "nct": "NCT07437547", "title": "BPC 157 for Acute Hamstring Muscle Strain Repair", "phase": "2", "status": "Recruiting" }, { "nct": "NCT07803250", "title": "Impact of BPC-157 on Recovery Following Rotator Cuff Repair Surgery", "phase": "1", "status": "Not yet recruiting" } ], "unknowns": [ "No published randomised controlled trial of BPC-157 for any musculoskeletal injury; registered hamstring and rotator-cuff trials have not reported", "No human pharmacokinetic data after oral, subcutaneous, nasal or transdermal use; FDA reports that plasma levels were undetectable after rectal enemas in early studies", "The full results of the 2005 ulcerative colitis trial were never published in a peer-reviewed journal", "Nearly all animal efficacy studies come from one research group, and independent replication is sparse", "No carcinogenicity studies and no repeat-dose toxicity studies longer than 28 days were available to FDA; clotting and liver findings in rats and dogs have not been followed up", "Which form (free base or acetate) and what purity is in gray-market products is unverified; FDA judged both forms not well characterised", "Regulatory status outside the US was not verified from regulator sources for this record" ], "mechanism": "The molecular target of BPC-157 has not been identified. In rodent and cell studies it has been associated with changes in nitric oxide signalling, blood vessel growth markers and growth-factor receptor expression; FDA's 2026 review describes its mechanism as poorly understood.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "bremelanotide", "names": { "inn": "bremelanotide", "common": [ "Bremelanotide", "PT-141" ], "codes": [ "PT-141" ], "brands": [ "Vyleesi" ], "cas": null }, "sequence": null, "sequence_note": "Cyclic heptapeptide: Ac-Nle-cyclo-(Asp-His-D-Phe-Arg-Trp-Lys-OH), per the US prescribing information. Contains norleucine and a D-amino acid, so no plain one-letter sequence is given. It differs from melanotan II only at the C-terminus (free acid rather than amide).", "class_by_jurisdiction": { "US": "A", "EU": "C", "UK": "C", "CA": "C", "AU": "C", "JP": null, "CN": null }, "what_it_is": "A synthetic cyclic peptide that activates melanocortin receptors. PT-141 is the development code for the same molecule. In the US it is an approved prescription medicine (Vyleesi) for one indication: acquired, generalized hypoactive sexual desire disorder in premenopausal women. No approval was found in the EU, UK, Canada or Australia. Outside that single US indication, material sold as \"PT-141\" powder is an unapproved product of unverified identity and purity, regardless of the molecule's approved status in the US.", "evidence": [ { "indication": "Hypoactive sexual desire disorder (HSDD) in premenopausal women", "tier": "E1", "human_rcts": 2, "human_trials_any": null, "summary": "Two phase 3 randomised placebo-controlled trials (RECONNECT; 1,267 women randomised in total) found small but statistically significant improvements in a sexual-desire score and reductions in desire-related distress compared with placebo. Nausea, flushing and headache were more frequent than with placebo. A 52-week open-label extension (684 entered, 272 completed) reported no new safety signals. An independent re-analysis of the trial data reported substantially higher adverse-event-related discontinuation on bremelanotide and criticised incomplete reporting of protocol-listed outcomes.", "citations": [ { "doi": "10.1097/aog.0000000000003500", "title": "Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder", "year": 2019, "finding": "Two phase 3 RCTs: greater increase in sexual desire score and reduction in related distress than placebo in premenopausal women" }, { "doi": "10.1097/aog.0000000000003514", "title": "Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder", "year": 2019, "finding": "52-week open-label extension; nausea (40.4%), flushing and headache were the most common treatment-related adverse events" }, { "doi": "10.1080/00224499.2021.1885601", "title": "Re-Analyzing Phase III Bremelanotide Trials for “Hypoactive Sexual Desire Disorder” in Women", "year": 2021, "finding": "Independent re-analysis based on FDA application data reporting higher adverse-event discontinuation on bremelanotide and incomplete outcome reporting in the phase 3 publication" } ], "trials_query": "bremelanotide" }, { "indication": "Erectile dysfunction in men (gray-market claim; not an approved use)", "tier": "E3", "human_rcts": 3, "human_trials_any": null, "summary": "Small randomised studies from the early 2000s tested an intranasal form in men: a phase 1 study in healthy men and men with mild-to-moderate erectile dysfunction reported erectile responses versus placebo, and a second study reported a larger erectile response when combined with sildenafil. A larger RCT in sildenafil non-responders is subject to a 2023 journal Expression of Concern. The approved US label states the product is not indicated in men or for improving sexual performance. No phase 3 evidence in men exists.", "citations": [ { "doi": "10.1038/sj.ijir.3901139", "title": "Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction", "year": 2004, "finding": "Erectile response greater than placebo in a small phase 1 study; flushing and nausea most common adverse events" }, { "doi": "10.1016/j.urology.2004.10.060", "title": "Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response", "year": 2005, "finding": "Greater erectile response with combined PT-141 and sildenafil than sildenafil alone in men with erectile dysfunction" }, { "doi": "10.1016/j.juro.2007.10.063", "title": "Salvage of Sildenafil Failures With Bremelanotide: A Randomized, Double-Blind, Placebo Controlled Study", "year": 2008, "finding": "Reported positive responses in sildenafil non-responders; the article is subject to a 2023 Expression of Concern" }, { "doi": "10.1097/ju.0000000000003117", "title": "Expression of Concern: Salvage of Sildenafil Failures With Bremelanotide: A Randomized, Double-Blind, Placebo Controlled Study", "year": 2023, "finding": "Journal of Urology Expression of Concern attached to the 2008 RCT" } ], "trials_query": "bremelanotide" } ], "safety": { "grade": "S2", "no_data_statement": true, "known_signals": [ { "signal": "Transient increase in blood pressure and decrease in heart rate after each dose", "evidence": "US prescribing information Warnings and Precautions 5.1; contraindicated in uncontrolled hypertension or known cardiovascular disease. Ambulatory monitoring studied in a dedicated trial.", "citation": { "doi": "10.1097/hjh.0000000000001221", "title": "Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide" } }, { "signal": "Focal hyperpigmentation (face, gingiva, breasts), not always resolving", "evidence": "US prescribing information Warnings and Precautions; higher risk with darker skin and with daily use.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210557s002lbl.pdf", "title": "VYLEESI (bremelanotide injection), for subcutaneous use" } }, { "signal": "Nausea, flushing, headache", "evidence": "Most frequent adverse events in phase 3 trials and the open-label extension.", "citation": { "doi": "10.1097/aog.0000000000003514", "title": "Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder" } }, { "signal": "Unknown composition of gray-market PT-141", "evidence": "No published analytical testing of gray-market material was identified; safety data from the approved product do not transfer to unverified powders. The approved US product is a single-dose autoinjector solution, not a powder.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210557s002lbl.pdf", "title": "VYLEESI (bremelanotide injection), for subcutaneous use" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "approved", "detail": "NDA 210557 (Vyleesi autoinjector), approved 21 June 2019; Drugs@FDA lists marketing status Prescription, current applicant Cosette. Approval is limited to premenopausal women with acquired, generalized HSDD; the label states it is not indicated in postmenopausal women, in men, or for improving sexual performance. Bremelanotide sold as research powder is not an FDA-approved product.", "source_url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210557s002lbl.pdf", "source_title": "VYLEESI prescribing information (FDA, label revision 10/2020)", "quote": "VYLEESI is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD)", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "unapproved", "detail": "No entry for bremelanotide in EMA's downloadable table of centrally authorised medicines (retrieved 2026-10-10). National authorisations in individual member states were not checked.", "source_url": "https://www.ema.europa.eu/en/medicines/download-medicine-data", "source_title": "EMA: Download medicine data", "quote": "This includes information on marketing authorisations of centrally authorised medicines and post-authorisation procedures.", "retrieved": "2026-10-10" }, { "jurisdiction": "UK", "status": "unapproved", "detail": "A search of the MHRA products database index for 'bremelanotide' returned no authorised product documents.", "source_url": "https://products.mhra.gov.uk/", "source_title": "MHRA Products", "quote": "Scientific reports about marketing authorisations for medicines", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "unapproved", "detail": "The Health Canada Drug Product Database API returns no product with active ingredient bremelanotide (https://health-products.canada.ca/api/drug/activeingredient/?lang=en&type=json&ingredientname=bremelanotide returned an empty list).", "source_url": "https://health-products.canada.ca/api/documentation/dpd-documentation-en.html", "source_title": "Health Canada Drug Product Database (DPD) API Guide", "quote": "The DPD contains product specific information on drugs approved for use in Canada.", "retrieved": "2026-10-10" }, { "jurisdiction": "AU", "status": "unapproved", "detail": "The TGA Product and Consumer Medicine Information repository returns no documents for bremelanotide, and bremelanotide is not named in the Poisons Standard (October 2026). Absence of a PI/CMI is strong but not conclusive evidence of no ARTG registration; the ARTG search itself could not be loaded.", "source_url": "https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=bremelanotide", "source_title": "TGA Product and Consumer Medicine Information search", "quote": "Trade Names and Active Ingredients containing bremelanotide . 0 Documents available.", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "not_prohibited", "wada_class": null, "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "trials": [ { "nct": "NCT02333071", "title": "1. Study to Evaluate the Efficacy/Safety of Bremelanotide in Premenopausal Women With Hypoactive Sexual Desire Disorder", "phase": "3", "status": "Completed" }, { "nct": "NCT02338960", "title": "2. Study to Evaluate the Efficacy/Safety of Bremelanotide in Premenopausal Women With Hypoactive Sexual Desire Disorder", "phase": "3", "status": "Completed" }, { "nct": "NCT06565611", "title": "A Phase 2 Study Evaluating the Co-Administration of Bremelanotide With Tirzepatide for the Treatment of Obesity", "phase": "2", "status": "Active, not recruiting" } ], "unknowns": [ "No phase 3 or adequately powered trial in men for any indication", "Efficacy and safety in postmenopausal women are not established", "Long-term cardiovascular effects of repeated transient blood-pressure rises are not characterised beyond 52 weeks", "No published analytical data on the identity, purity, sterility or dose accuracy of gray-market PT-141", "Whether the focal hyperpigmentation seen with frequent use resolves in all cases is not established" ], "mechanism": "Bremelanotide is a non-selective melanocortin receptor agonist; per its US label, binding at MC1R and MC4R is most relevant at therapeutic exposure, MC1R binding increases pigmentation, and the mechanism in HSDD is unknown.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "cagrilintide", "names": { "inn": "cagrilintide", "common": [ "Cagrilintide", "CagriSema (fixed co-formulation with semaglutide)" ], "codes": [ "NNC0174-0833" ], "brands": [], "cas": null }, "sequence": null, "sequence_note": "Lipidated (fatty-acid acylated), long-acting analogue of human amylin with amino-acid substitutions; design described in Kruse et al., J Med Chem 2021. Full modified sequence not reproduced here because it was not verified against a regulator document.", "class_by_jurisdiction": { "US": "B", "EU": "B", "UK": "B", "CA": "B", "AU": "B", "JP": null, "CN": null }, "what_it_is": "A synthetic, long-acting analogue of amylin, a pancreatic hormone involved in satiety, developed by Novo Nordisk for weight management, alone and in a fixed combination with semaglutide (CagriSema). It is investigational: no product containing it was found in the US, EU, UK, Canadian or Australian regulator databases checked on the retrieval date. Material sold online under this name is not the sponsor's product and is of unverified identity and purity.", "evidence": [ { "indication": "Weight management in adults with overweight or obesity (cagrilintide alone)", "tier": "E2", "human_rcts": 2, "human_trials_any": null, "summary": "One adequately sized phase 2 dose-finding RCT (706 participants, 26 weeks) found greater mean weight reduction with every cagrilintide dose than with placebo, with gastrointestinal adverse events (mainly nausea) more frequent than with placebo. The phase 3a REDEFINE 1 trial included a cagrilintide-alone arm (302 participants) as a comparator, but its published primary comparison was the combination against placebo. Dedicated phase 3 monotherapy trials are registered and have not reported. Published results for cagrilintide alone beyond 68 weeks are absent.", "citations": [ { "doi": "10.1016/s0140-6736(21)01751-7", "title": "Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial", "year": 2021, "finding": "All cagrilintide doses produced greater 26-week weight reduction than placebo in adults with overweight or obesity; nausea was the most frequent adverse event" }, { "doi": "10.1056/nejmoa2502081", "title": "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity", "year": 2025, "finding": "Phase 3a RCT with a cagrilintide-alone comparator arm; primary analysis compared the combination with placebo over 68 weeks" } ], "trials_query": "cagrilintide" }, { "indication": "Weight management in adults with overweight or obesity, with or without type 2 diabetes (cagrilintide plus semaglutide, CagriSema)", "tier": "E1", "human_rcts": 2, "human_trials_any": null, "summary": "Two phase 3a placebo-controlled RCTs report consistent results over 68 weeks. In adults without diabetes (REDEFINE 1, 3417 randomised) mean body-weight change was -20.4% with the combination versus -3.0% with placebo. In adults with type 2 diabetes (REDEFINE 2, 1206 randomised) it was -13.7% versus -3.4%, with more participants reaching glycated haemoglobin of 6.5% or less. Gastrointestinal adverse events were common (79.6% versus 39.9% in REDEFINE 1). Neither trial's registry record had posted results on the retrieval date. Cardiovascular outcome data (REDEFINE 3) are not yet reported.", "citations": [ { "doi": "10.1056/nejmoa2502081", "title": "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity", "year": 2025, "finding": "Greater 68-week weight reduction with cagrilintide-semaglutide than placebo in adults without diabetes" }, { "doi": "10.1056/nejmoa2502082", "title": "Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes", "year": 2025, "finding": "Greater 68-week weight reduction and glycaemic improvement than placebo in adults with type 2 diabetes" } ], "trials_query": "cagrilintide" } ], "safety": { "grade": "S2", "no_data_statement": true, "known_signals": [ { "signal": "Gastrointestinal adverse events (nausea, vomiting, diarrhoea, constipation)", "evidence": "Reported more often than placebo in the phase 2 monotherapy RCT and in the phase 3a combination RCTs; mostly transient and mild to moderate. No post-marketing data exist because no product is approved.", "citation": { "doi": "10.1056/nejmoa2502081", "title": "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "investigational", "detail": "No approved application. The openFDA Drugs@FDA endpoint returns no application with cagrilintide as an active ingredient (query: products.active_ingredients.name:CAGRILINTIDE*). Sponsored phase 3 trials are registered (e.g. NCT05567796, NCT07220642). Whether a marketing application is under FDA review was not verified from an FDA source.", "source_url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:CAGRILINTIDE*", "source_title": "openFDA Drugs@FDA API (FDA)", "quote": "No matches found!", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "investigational", "detail": "Absent from EMA's downloadable table of centrally authorised medicines (retrieved 2026-10-10) and absent from EMA's monthly lists of new medicines under CHMP evaluation for August, September and October 2026.", "source_url": "https://www.ema.europa.eu/en/medicines/medicines-human-use-under-evaluation", "source_title": "EMA: Medicines for human use under evaluation", "quote": "publishes an updated list of medicines for human use currently under evaluation", "retrieved": "2026-10-10" }, { "jurisdiction": "UK", "status": "investigational", "detail": "A search of the MHRA products database index for 'cagrilintide' returned no authorised product documents.", "source_url": "https://products.mhra.gov.uk/", "source_title": "MHRA Products", "quote": "Scientific reports about marketing authorisations for medicines", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "investigational", "detail": "The Health Canada Drug Product Database API returns no product with active ingredient cagrilintide (https://health-products.canada.ca/api/drug/activeingredient/?lang=en&type=json&ingredientname=cagrilintide returned an empty list).", "source_url": "https://health-products.canada.ca/api/documentation/dpd-documentation-en.html", "source_title": "Health Canada Drug Product Database (DPD) API Guide", "quote": "The DPD contains product specific information on drugs approved for use in Canada.", "retrieved": "2026-10-10" }, { "jurisdiction": "AU", "status": "investigational", "detail": "The TGA Product and Consumer Medicine Information repository returns no documents for cagrilintide. Absence of a PI/CMI is strong but not conclusive evidence of no ARTG registration; the ARTG search itself could not be loaded.", "source_url": "https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=cagrilintide", "source_title": "TGA Product and Consumer Medicine Information search", "quote": "Trade Names and Active Ingredients containing cagrilintide . 0 Documents available.", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S0", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "trials": [ { "nct": "NCT03856047", "title": "Research Study Investigating How Well NNC0174-0833 Works in People Suffering From Overweight or Obesity.", "phase": "2", "status": "Completed" }, { "nct": "NCT05567796", "title": "A Research Study to See How Well CagriSema Helps People With Excess Body Weight Lose Weight", "phase": "3", "status": "Active, not recruiting" }, { "nct": "NCT05394519", "title": "A Research Study to See How Well CagriSema Helps People With Type 2 Diabetes and Excess Body Weight Lose Weight", "phase": "3", "status": "Completed" }, { "nct": "NCT06131437", "title": "A Research Study to See How Well CagriSema Compared to Tirzepatide Helps People With Obesity Lose Weight", "phase": "3", "status": "Completed" }, { "nct": "NCT05669755", "title": "REDEFINE 3: A Research Study to See the Effects of CagriSema in People Living With Diseases in the Heart and Blood Vessels", "phase": "3", "status": "Active, not recruiting" }, { "nct": "NCT07220642", "title": "Weight Loss in People Living With Overweight or Obesity Following Treatment With Cagrilintide", "phase": "3", "status": "Active, not recruiting" } ], "unknowns": [ "No published phase 3 efficacy results for cagrilintide as a stand-alone product; dedicated monotherapy phase 3 trials have not reported", "No cardiovascular outcome data; REDEFINE 3 has not reported", "No safety data beyond the 68-week trial periods and no post-marketing surveillance, because no product is approved", "No data of any kind on the identity, purity or sterility of material sold outside the sponsor's trials under the name cagrilintide", "Effects in pregnancy and lactation are not established in humans" ], "mechanism": "Cagrilintide is a lipidated, long-acting analogue of the pancreatic hormone amylin. Endogenous amylin signalling is involved in satiety and the rate of gastric emptying.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "cjc-1295", "names": { "inn": null, "common": [ "CJC-1295", "CJC-1295 with DAC", "CJC 1295" ], "codes": [ "CJC-1295" ], "brands": [], "cas": null }, "sequence": null, "sequence_note": "A modified GHRH(1-29) amide analogue with a C-terminal reactive group designed to bind covalently to circulating albumin (the developer's 'drug affinity complex'), which extended its half-life to several days in humans. A 29-residue amidated GHRH analogue without the albumin-binding group has been identified in material sold under the CJC-1295 name.", "class_by_jurisdiction": { "US": "C", "EU": "C", "UK": null, "CA": "C", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic, long-acting analogue of growth hormone-releasing hormone (GHRH) developed by ConjuChem in the 2000s. Its only registered efficacy trial, in people with HIV and abdominal fat, was terminated in 2006 and never reported. It has no approval anywhere checked and no active sponsor. It is sold as a \"research chemical\" with claims of muscle gain, fat loss, better sleep and \"anti-ageing\". FDA has identified serious adverse events associated with it.", "evidence": [ { "indication": "Raising GH and IGF-1 levels (pharmacodynamic marker, healthy adults)", "tier": "E3", "human_rcts": 0, "human_trials_any": 2, "summary": "Two randomised, placebo-controlled, ascending-dose studies in healthy adults (lasting 28 and 49 days) found dose-dependent rises in plasma GH and IGF-1 lasting days after a single dose, with an estimated half-life of about 6 to 8 days; no serious adverse reactions were reported. A separate uncontrolled before-and-after study in healthy young men found raised trough and mean GH with preserved pulsatility, and higher IGF-1, one week after a single dose. These are small, short studies of a hormone marker, not of any clinical outcome.", "citations": [ { "doi": "10.1210/jc.2005-1536", "title": "Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor I Secretion by CJC-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults", "year": 2006, "finding": "Dose-dependent increases in plasma GH and IGF-1 lasting days in healthy adults in two randomised, placebo-controlled dose-escalation studies; estimated half-life 5.8 to 8.1 days" }, { "doi": "10.1210/jc.2006-1702", "title": "Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long-Acting GH-Releasing Hormone Analog", "year": 2006, "finding": "Raised trough and mean GH and IGF-1 with preserved GH pulsatility one week after a single dose in healthy young men (uncontrolled)" } ], "trials_query": "CJC-1295" }, { "indication": "Muscle gain, fat loss, recovery, sleep and anti-ageing (gray-market claims)", "tier": "E8", "human_rcts": 0, "human_trials_any": 0, "summary": "No published study in humans or animals has tested any of these outcomes. Published human studies measured only hormone levels (GH and IGF-1) in healthy adults over weeks (see the pharmacodynamic entry above). Raised hormone levels are a laboratory measure, not evidence of muscle gain, fat loss, better sleep or any health benefit.", "citations": [ { "doi": "10.1002/dta.233", "title": "Identification of CJC‐1295, a growth‐hormone‐releasing peptide, in an unknown pharmaceutical preparation", "year": 2010, "finding": "Product-identity finding, not efficacy: a seized preparation contained a 29-residue amidated peptide consistent with the sequence marketed as CJC-1295" } ], "trials_query": "CJC-1295" }, { "indication": "Visceral fat in people with HIV", "tier": "E8", "human_rcts": 0, "human_trials_any": 0, "summary": "A randomised placebo-controlled Phase 2 trial in 120 people with HIV-associated visceral obesity (NCT00267527, ConjuChem) began in December 2005 and is registered as terminated in 2006. No reason is given on the registry and no results were posted or published, so it is not counted as a published trial. No published study in humans or animals has tested CJC-1295 on visceral fat.", "citations": [], "trials_query": "CJC-1295" }, { "indication": "Growth in GHRH deficiency", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "In mice genetically lacking GHRH, five weeks of treatment from one week of age normalised body weight, length and body composition when given every 24 hours, with lesser effects at longer intervals. This is a deficiency model; it does not show effects in animals or people with normal GHRH. No human growth study exists.", "citations": [ { "doi": "10.1152/ajpendo.00201.2006", "title": "Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse", "year": 2006, "finding": "Normalised body weight, length and body composition in GHRH-knockout mice" } ], "trials_query": "CJC-1295" } ], "safety": { "grade": "S3", "no_data_statement": true, "known_signals": [ { "signal": "Increased heart rate and systemic vasodilatory reaction", "evidence": "FDA's compounding safety-risk summary states it has identified serious adverse events associated with CJC-1295, including increased heart rate and a systemic vasodilatory reaction, and that available clinical data are limited. The underlying case details are not published there.", "citation": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks" } }, { "signal": "Immunogenicity and impurity concerns", "evidence": "FDA states compounded CJC-1295 may pose a risk of immunogenicity for certain routes and raises peptide-impurity and characterisation concerns.", "citation": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "Not approved: no application found in Drugs@FDA (openFDA query, retrieval date). CJC-1295 was placed in Category 2 (significant safety risks) of FDA's 503A interim policy; it now appears on FDA's list of substances 'nominated but withdrawn', i.e. removed from Category 2 because the nominator withdrew the nomination, not because FDA resolved the safety concerns, which the page still states.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026)", "quote": "FDA has identified serious adverse events associated with CJC-1295 including increased heart rate and systemic vasodilatory reaction. Available clinical data are limited.", "retrieved": "2026-10-10" }, { "jurisdiction": "US", "status": "unapproved", "detail": "CJC-1295 does not appear in Category 1, 2 or 3 of FDA's list of bulk drug substances nominated for 503A compounding (updated 14 May 2026). It is not on the 503A bulks list and is not a component of any FDA-approved drug product.", "source_url": "https://www.fda.gov/media/94155/download", "source_title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (Updated May 14, 2026)", "quote": "Category 1: Bulk Drug Substances Under Evaluation", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "unapproved", "detail": "No product containing CJC-1295 appears in EMA's downloadable medicines dataset (2,748 records, generated 10 Oct 2026), which covers centrally authorised medicines, refusals and withdrawn applications. National authorisations were not checked individually.", "source_url": "https://www.ema.europa.eu/en/medicines/download-medicine-data", "source_title": "Download medicine data | European Medicines Agency (EMA)", "quote": "This includes information on marketing authorisations of centrally authorised medicines and post-authorisation procedures.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "unapproved", "detail": "Queries of Health Canada's Drug Product Database for the active ingredient and brand name CJC-1295 returned no products under any status on the retrieval date.", "source_url": "https://health-products.canada.ca/dpd-bdpp/?lang=eng", "source_title": "Drug Product Database online query", "quote": "Search by drug identification number", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S2.2.4", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "growth hormone-releasing hormone (GHRH) and its analogues (e.g. CJC-1293, CJC-1295, sermorelin and tesamorelin)" }, "trials": [ { "nct": "NCT00267527", "title": "A Study to Evaluate CJC 1295 in HIV Patients With Visceral Obesity", "phase": "2", "status": "Terminated" } ], "unknowns": [ "No human efficacy data for any clinical outcome; the published human studies (two small randomised placebo-controlled studies and one uncontrolled study, all in healthy adults) measured only GH and IGF-1 and lasted under two months", "No human safety data beyond short dose-finding studies in small numbers of healthy adults; no data on repeated exposure over months or years", "Why the only efficacy trial (NCT00267527) was terminated is not stated on the registry, and its data were never reported", "Effects of sustained elevation of GH and IGF-1 from a long-acting analogue on glucose metabolism, cancer risk or the heart are unstudied", "Products sold as CJC-1295 may contain a different peptide: a 29-residue analogue without the albumin-binding group was identified in a seized preparation, so the half-life and effects of what is in a given vial are unknown", "Regulatory status in the UK, Australia, Japan and China was not verified from regulator sources for this record" ], "mechanism": "CJC-1295 is a GHRH analogue designed to bind albumin after absorption, prolonging its action; in rats it activated pituitary GHRH receptors, and in healthy adults it raised GH and IGF-1 for several days.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "desmopressin", "names": { "inn": "desmopressin", "common": [ "Desmopressin", "Desmopressin acetate", "DDAVP", "1-deamino-8-D-arginine vasopressin" ], "codes": [ "DDAVP", "SER120" ], "brands": [ "DDAVP", "Nocdurna" ], "cas": null }, "sequence": null, "sequence_note": "Synthetic analogue of arginine vasopressin: 3-mercaptopropionic acid (deaminated Cys1)-Tyr-Phe-Gln-Asn-Cys-Pro-D-Arg-Gly-NH2, disulfide-bridged; contains a D-arginine and a C-terminal amide, so no standard one-letter sequence is given.", "class_by_jurisdiction": { "US": "A", "EU": null, "UK": null, "CA": "A", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic nine-residue analogue of the pituitary hormone vasopressin, modified to act mainly on kidney water reabsorption with little effect on blood pressure. It has been an approved prescription drug for decades in tablet, nasal, sublingual and injectable forms. Labelled uses include central diabetes insipidus, primary nocturnal enuresis, nocturia due to nocturnal polyuria, and, for the injectable form, certain bleeding disorders.", "evidence": [ { "indication": "Nocturia due to nocturnal polyuria in adults", "tier": "E1", "human_rcts": 3, "human_trials_any": 3, "summary": "Several adequately sized randomised, double-blind, placebo-controlled phase 3 trials of low-strength sublingual and nasal formulations reported modest reductions in night-time voids compared with placebo. Effect sizes over placebo were small in absolute terms. Hyponatraemia was the principal safety concern and was more frequent in older participants.", "citations": [ { "doi": "10.1016/j.juro.2012.12.112", "title": "Efficacy and Safety of Low Dose Desmopressin Orally Disintegrating Tablet in Men with Nocturia: Results of a Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study", "year": 2013, "finding": "Greater reduction in nocturnal voids than placebo in men with nocturia in a randomised placebo-controlled trial" }, { "doi": "10.1016/j.juro.2018.04.050", "title": "Efficacy and Safety of SER120 Nasal Spray in Patients with Nocturia: Pooled Analysis of 2 Randomized, Double-Blind, Placebo Controlled, Phase 3 Trials", "year": 2018, "finding": "Pooled analysis of two placebo-controlled phase 3 trials reported fewer nocturnal voids with the nasal formulation than with placebo" } ], "trials_query": "desmopressin nocturia" }, { "indication": "Primary nocturnal enuresis in children", "tier": "E1", "human_rcts": null, "human_trials_any": null, "summary": "A Cochrane systematic review of randomised trials found that desmopressin reduced the number of wet nights compared with placebo while it was being taken, but the review found no evidence that the benefit persisted after treatment stopped. The exact number of included RCTs is not restated here.", "citations": [ { "doi": "10.1002/14651858.CD002112", "title": "Desmopressin for nocturnal enuresis in children", "year": 2002, "finding": "Fewer wet nights than placebo during treatment in children with nocturnal enuresis; no sustained effect after stopping" } ], "trials_query": "desmopressin enuresis" }, { "indication": "Central diabetes insipidus", "tier": "E4", "human_rcts": null, "human_trials_any": null, "summary": "Use in central diabetes insipidus rests on early uncontrolled clinical studies from the 1970s showing an antidiuretic response, and on long clinical use. No placebo-controlled trial is cited here; in a condition with a direct physiological replacement rationale, randomised placebo-controlled trials have not been the basis of approval.", "citations": [ { "doi": "10.1530/acta.0.069s052", "title": "THERAPEUTIC RESPONSE OF CENTRAL DIABETES INSIPIDUS ON NASAL APPLICATION OF A NEW SYNTHETIC ANALOGUE OF VASOPRESSIN (1-DEAMINO-8-D-ARGININE-VASOPRESSIN (DDAVP))", "year": 1972, "finding": "Early clinical report of antidiuretic response to nasal desmopressin in patients with central diabetes insipidus" } ], "trials_query": "desmopressin diabetes insipidus" }, { "indication": "Haemophilia A and von Willebrand disease (bleeding prevention)", "tier": "E4", "human_rcts": null, "human_trials_any": null, "summary": "The use of desmopressin to raise factor VIII and von Willebrand factor levels in mild haemophilia A and type 1 von Willebrand disease was established in uncontrolled clinical studies beginning in 1977. No randomised trial with bleeding outcomes is cited here.", "citations": [ { "doi": "10.1016/s0140-6736(77)91197-7", "title": "1-DEAMINO-8-D-ARGININE VASOPRESSIN: A NEW PHARMACOLOGICAL APPROACH TO THE MANAGEMENT OF HAEMOPHILIA AND VON WILLEBRAND'S DISEASE", "year": 1977, "finding": "Uncontrolled clinical study reporting rises in factor VIII and von Willebrand factor after desmopressin in patients with haemophilia and von Willebrand disease" } ], "trials_query": "desmopressin hemophilia" } ], "safety": { "grade": "S1", "no_data_statement": false, "known_signals": [ { "signal": "Hyponatraemia", "evidence": "A systematic review and meta-analysis found hyponatraemia to be a recognised risk in older adults treated with desmopressin for nocturia. Severe hyponatraemia can cause seizures.", "citation": { "doi": "10.1002/nau.20038", "title": "The risk of hyponatremia in older adults using desmopressin for nocturia: A systematic review and meta‐analysis" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "approved", "detail": "Drugs@FDA lists DDAVP tablets (NDA 019955, Ferring) with marketing status Prescription. Other desmopressin NDAs include DDAVP injection (NDA 018938, Prescription). The DDAVP nasal products under NDA 017922 and Nocdurna (NDA 022517) are listed as Discontinued.", "source_url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019955", "source_title": "Drugs@FDA: FDA-Approved Drugs - NDA 019955 (DDAVP)", "quote": "09/06/1995 ORIG-1 Approval Type 3 - New Dosage Form STANDARD", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "approved", "detail": "Health Canada Drug Product Database lists the DDAVP injectable product (Ferring Inc) with current status Marketed. DDAVP Spray, DDAVP Rhinyle and DDAVP tablet entries checked were listed as Cancelled Post Market.", "source_url": "https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=13867", "source_title": "Drug Product Database: Product information - DDAVP injection", "quote": "Current status: Marketed Current status date: 1993-12-31 Original market date: See footnote 1 1993-12-31", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S5", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "mannitol; Desmopressin; Probenecid; and other substances with a similar chemical structure or similar biological effect(s)." }, "trials": [ { "nct": "NCT01262456", "title": "Investigation of the Superiority Effect of Orally Disintegrating Desmopressin Tablets to Placebo in Terms of Night Voids Reduction in Nocturia Adult Male Patients", "phase": "3", "status": "Completed" }, { "nct": "NCT01223937", "title": "Investigation of the Superiority Effect of Desmopressin to Placebo in Terms of Night Voids Reduction in Nocturia Adult Female Patients", "phase": "3", "status": "Completed" } ], "unknowns": [ "No randomised placebo-controlled trial with clinical outcomes underpins use in central diabetes insipidus; the evidence is historical and uncontrolled", "Whether the small average reduction in night-time voids in nocturia trials outweighs hyponatraemia risk in people over 65 is not settled by the cited trials", "Benefit in childhood enuresis after treatment stops was not demonstrated in the cited review", "Status in the EU (national authorisations), UK, Australia, Japan and China was not verified from regulator sources for this record" ], "mechanism": "Desmopressin is a selective vasopressin V2 receptor agonist; in human studies it reduces urine output by increasing water reabsorption in the kidney collecting duct and raises circulating factor VIII and von Willebrand factor levels.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "dihexa", "names": { "inn": null, "common": [ "Dihexa", "Dihexa acetate", "N-hexanoic-Tyr-Ile-(6) aminohexanoic amide" ], "codes": [], "brands": [], "cas": null }, "sequence": null, "sequence_note": "N-hexanoic-Tyr-Ile-(6) aminohexanoic amide: a modified dipeptide (Tyr-Ile) with an N-terminal hexanoyl group and a C-terminal 6-aminohexanoic amide; non-standard groups, so no one-letter sequence is given.", "class_by_jurisdiction": { "US": "C", "EU": "C", "UK": null, "CA": "C", "AU": null, "JP": null, "CN": null }, "what_it_is": "A small, chemically modified peptide derived from angiotensin IV, designed at a US university to be stable and to reach the brain when taken by mouth. It is sold online as a research chemical with claims of improving memory and cognition. It has never been tested in people in any published study identified, and no approved medicine contains it. Two journal papers from the developing laboratory on the angiotensin IV/HGF approach were retracted in 2025, and the original dihexa report carries an expression of concern.", "evidence": [ { "indication": "Cognitive enhancement / dementia", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "All efficacy data are from rodents. The developing group reported that dihexa reversed scopolamine-induced and age-related deficits in a water-maze test in rats; the journal attached an expression of concern to that report in 2021. A separate group reported improved spatial learning in APP/PS1 Alzheimer-model mice. A 2014 paper from the developing laboratory proposing that these effects depend on the HGF/c-Met system was retracted in 2025. No human study of any kind was identified.", "citations": [ { "doi": "10.1124/jpet.112.199497", "title": "Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia Agents", "year": 2013, "finding": "Reversed scopolamine-induced and age-related water-maze deficits in rats (report subject to a 2021 expression of concern)" }, { "doi": "10.3390/brainsci11111487", "title": "AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway", "year": 2021, "finding": "Improved spatial learning in the water maze and reduced glial activation in APP/PS1 Alzheimer-model mice" }, { "doi": "10.1016/j.jpet.2025.103567", "title": "Retraction notice to “The Procognitive and Synaptogenic Effects of Angiotensin IV–Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System” [J Pharmacol Exp Ther 351 (2014) 390-402]", "year": 2025, "finding": "Retraction of the 2014 rodent and cell report linking these peptides' effects to the HGF/c-Met system" } ], "trials_query": "dihexa" } ], "safety": { "grade": "S5", "no_data_statement": true, "known_signals": [] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "No FDA-approved application: openFDA Drugs@FDA returns no application with a dihexa active ingredient (query: products.active_ingredients.name:DIHEXA*). openFDA states its data are unvalidated.", "source_url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:DIHEXA*", "source_title": "openFDA Drugs@FDA API (FDA)", "quote": "No matches found!", "retrieved": "2026-10-10" }, { "jurisdiction": "US", "status": "unapproved", "detail": "Dihexa acetate appears on FDA's list of bulk drug substances previously in Category 2 (significant safety risks) of the compounding interim policy whose nominations were withdrawn by the nominators. FDA's safety statement remains on the page.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026)", "quote": "FDA has not identified any human exposure data on drug products containing dihexa acetate administered via any route of administration.", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "unapproved", "detail": "No product containing dihexa appears in EMA's downloadable medicines dataset (generated 10 Oct 2026), which covers centrally authorised medicines, refusals and withdrawn applications. National authorisations were not checked individually.", "source_url": "https://www.ema.europa.eu/en/medicines/download-medicine-data", "source_title": "Download medicine data | European Medicines Agency (EMA)", "quote": "This includes information on marketing authorisations of centrally authorised medicines and post-authorisation procedures.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "unapproved", "detail": "A query of Health Canada's Drug Product Database API for the active ingredient dihexa returned no products on the retrieval date; a brand-name query matched only unrelated veterinary teat-dip products whose names begin with the same letters.", "source_url": "https://health-products.canada.ca/dpd-bdpp/?lang=eng", "source_title": "Drug Product Database online query", "quote": "Search by drug identification number", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S0", "detail": "Dihexa is not named on the 2026 Prohibited List; as a substance with no governmental approval for human use identified, it falls under class S0.", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "unknowns": [ "No human data of any kind were identified: no pharmacokinetic, safety or efficacy study in people", "FDA states it has not identified any human exposure data and lacks information on whether dihexa would cause harm in humans", "The proposed mechanism through hepatocyte growth factor and its receptor c-Met is a pathway also involved in cell growth and cancer; long-term effects of stimulating it in humans are unstudied", "Independent replication of the original rat findings is limited to one mouse study identified, and the founding reports are under an expression of concern or retracted", "Status in the UK, Australia, Japan and China was not verified from regulator sources for this record" ], "mechanism": "Dihexa was derived from angiotensin IV. Its developers proposed that it acts by enhancing hepatocyte growth factor signalling through the c-Met receptor; a key 2014 paper supporting that mechanism has been retracted, so the mechanism is not established.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "elamipretide", "names": { "inn": "elamipretide", "common": [ "Elamipretide", "SS-31", "MTP-131", "Bendavia" ], "codes": [ "SS-31", "MTP-131" ], "brands": [ "Forzinity" ], "cas": null }, "sequence": null, "sequence_note": "Synthetic tetrapeptide D-Arg-2,6-dimethyl-Tyr-Lys-Phe-NH2 (FDA label: D-arginyl-2,6-dimethyl-L-tyrosyl-L-lysyl-L-phenylalaninamide); contains a D-amino acid and a non-standard dimethyltyrosine, so no one-letter sequence is given.", "class_by_jurisdiction": { "US": "A", "EU": null, "UK": null, "CA": null, "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic four-residue peptide that binds cardiolipin, a lipid of the inner mitochondrial membrane. The US FDA granted it accelerated approval in September 2025 (brand Forzinity) for muscle strength in Barth syndrome, a rare inherited mitochondrial disease, on the basis of an intermediate endpoint, with a confirmatory trial required. It has also been tested in primary mitochondrial myopathy, dry macular degeneration and heart failure. Under the research name SS-31 it is also sold outside medical channels with anti-ageing and mitochondrial-health claims.", "evidence": [ { "indication": "Barth syndrome (muscle strength, exercise capacity, fatigue)", "tier": "E3", "human_rcts": 1, "human_trials_any": 1, "summary": "The only controlled evidence is TAZPOWER, a randomised, double-blind, placebo-controlled crossover trial in 12 males with Barth syndrome. In the randomised part neither primary endpoint (six-minute walk distance and a Barth symptom score) was met. In the open-label extension, without a concurrent control group, walk distance, symptom scores and knee extensor strength improved from baseline. FDA's accelerated approval rests on knee extensor strength, an intermediate endpoint, and FDA requires a randomised placebo-controlled confirmatory trial (registered as 4TAZPower).", "citations": [ { "doi": "10.1038/s41436-020-01006-8", "title": "A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism", "year": 2021, "finding": "Neither primary endpoint was met in the randomised crossover phase in 12 patients; improvements from baseline were reported in the uncontrolled open-label extension" } ], "trials_query": "elamipretide Barth" }, { "indication": "Primary mitochondrial myopathy", "tier": "E3", "human_rcts": 3, "human_trials_any": null, "summary": "Two small randomised trials (MMPOWER, 36 participants, five days of intravenous dosing; MMPOWER-2, 30 participants, four-week crossover) did not meet their primary walk-test endpoint at conventional significance, though some secondary and patient-reported measures favoured elamipretide. The larger phase 3 trial (MMPOWER-3, 218 participants, 24 weeks) did not meet either primary endpoint; the between-group difference in walk distance was close to zero. The randomised evidence is therefore conflicting at best, and the largest trial was negative.", "citations": [ { "pmid": 37268435, "title": "Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial", "year": 2023, "finding": "No difference from placebo in six-minute walk distance or fatigue score at 24 weeks in 218 participants with primary mitochondrial myopathy" }, { "doi": "10.1002/jcsm.12559", "title": "A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy", "year": 2020, "finding": "Primary walk-test endpoint not statistically significant over four weeks in 30 participants; patient-reported fatigue scores favoured elamipretide" }, { "doi": "10.1212/WNL.0000000000005255", "title": "Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy", "year": 2018, "finding": "Highest intravenous dose group walked farther than placebo after five days in 36 participants (unadjusted comparison not significant)" } ], "trials_query": "elamipretide mitochondrial myopathy" }, { "indication": "Dry age-related macular degeneration with geographic atrophy", "tier": "E3", "human_rcts": 1, "human_trials_any": null, "summary": "ReCLAIM-2, a randomised, double-masked, placebo-controlled phase 2 trial in 176 patients treated for 48 weeks, did not meet either primary endpoint (low-luminance visual acuity and growth of the atrophic area). Differences favouring elamipretide were reported on ellipsoid-zone imaging measures with nominal p-values. A phase 3 trial (ReNEW) is registered; no results were identified.", "citations": [ { "doi": "10.1016/j.xops.2024.100628", "title": "ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation", "year": 2024, "finding": "Primary visual-acuity and atrophy-growth endpoints not met in 176 patients; nominal differences on retinal imaging measures" } ], "trials_query": "elamipretide macular degeneration" }, { "indication": "Age-related decline in muscle function and exercise capacity (anti-ageing claims)", "tier": "E3", "human_rcts": 1, "human_trials_any": 1, "summary": "This is the main gray-market claim for SS-31. In aged female mice, eight weeks of treatment increased in-vivo mitochondrial ATP production and treadmill endurance. The one human randomised trial identified gave a single intravenous infusion to 39 healthy adults aged 60 to 85: a measure of maximal mitochondrial ATP production in a hand muscle rose briefly after infusion, was not different at day 7, and fatigue resistance did not change. No human trial has tested longer-term use for ageing, frailty or exercise performance.", "citations": [ { "doi": "10.1371/journal.pone.0253849", "title": "In vivo mitochondrial ATP production is improved in older adult skeletal muscle after a single dose of elamipretide in a randomized trial", "year": 2021, "finding": "Single infusion transiently raised a spectroscopic measure of mitochondrial capacity in older adults; no effect on muscle fatigue resistance" }, { "doi": "10.1016/j.freeradbiomed.2018.12.031", "title": "Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice", "year": 2019, "finding": "Eight weeks of SS-31 increased treadmill endurance and muscle mitochondrial ATP production in aged female mice" } ], "trials_query": "elamipretide" } ], "safety": { "grade": "S2", "no_data_statement": false, "known_signals": [ { "signal": "Injection site reactions", "evidence": "Injection site reactions were the most common adverse event in controlled trials; in the MMPOWER-2 crossover trial they were reported in 80% of participants during elamipretide treatment, mostly mild.", "citation": { "doi": "10.1002/jcsm.12559", "title": "A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy" } }, { "signal": "Hypersensitivity reactions", "evidence": "The US label warns that hypersensitivity reactions, including serious allergic reactions requiring emergency medical intervention, have been reported, and lists serious hypersensitivity as a contraindication.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf", "title": "FORZINITY (elamipretide) injection, for subcutaneous use" } }, { "signal": "Eosinophilia", "evidence": "The US label reports frequent increases in blood eosinophil counts in studies lasting 30 days or more, peaking around 90 days; these were not associated with clinical manifestations.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf", "title": "FORZINITY (elamipretide) injection, for subcutaneous use" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "approved", "detail": "On 19 September 2025 FDA granted accelerated approval to Forzinity (elamipretide) injection, Stealth BioTherapeutics, NDA 215244, for Barth syndrome. Approval is based on knee extensor muscle strength, an intermediate endpoint; FDA requires a randomised, double-blind, placebo-controlled confirmatory trial, and continued approval may be contingent on it.", "source_url": "https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-treatment-barth-syndrome", "source_title": "FDA Grants Accelerated Approval to First Treatment for Barth Syndrome (FDA News Release, September 19, 2025)", "quote": "Today, the U.S. Food and Drug Administration granted accelerated approval to Forzinity (elamipretide) injection as the first treatment for Barth syndrome", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "not_prohibited", "wada_class": null, "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "trials": [ { "nct": "NCT03098797", "title": "A Trial to Evaluate Safety, Tolerability and Efficacy of Elamipretide in Subjects With Barth Syndrome", "phase": "2/3", "status": "Completed" }, { "nct": "NCT07531251", "title": "Clinical Trial in Patients With Barth Syndrome- 4TAZPower", "phase": "4", "status": "Recruiting" }, { "nct": "NCT03323749", "title": "A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension", "phase": "3", "status": "Terminated" }, { "nct": "NCT03891875", "title": "ReCLAIM-2 Study to Evaluate Safety,Efficacy & Pharmacokinetics of Elamipretide in Subjects With AMD With Non-central GA", "phase": "2", "status": "Completed" } ], "unknowns": [ "Whether the knee-strength improvement underlying the US accelerated approval translates into functional benefit in Barth syndrome; the required confirmatory randomised trial has not reported", "The approved-use evidence base is 12 patients; long-term safety beyond the small Barth syndrome extension cohort and a few hundred trial participants elsewhere is not characterised", "No human trial has tested repeated use in healthy older adults for ageing, frailty or exercise capacity; the human ageing evidence is a single-infusion biomarker study", "Not named on the 2026 WADA Prohibited List; since the 2025 US approval it falls outside S0, which covers only substances with no current approval anywhere", "Regulatory status outside the US was not verified from regulator sources for this record" ], "mechanism": "Elamipretide is a cell-permeable peptide that concentrates at the inner mitochondrial membrane and binds cardiolipin; in aged mice it increased in-vivo mitochondrial ATP production in skeletal muscle.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "epitalon", "names": { "inn": null, "common": [ "Epitalon", "Epithalon", "Epithalone", "AEDG peptide", "Ala-Glu-Asp-Gly" ], "codes": [], "brands": [], "cas": null }, "sequence": "AEDG", "sequence_note": "Synthetic tetrapeptide Ala-Glu-Asp-Gly. It was designed on the basis of epithalamin, a peptide extract of bovine pineal gland; epithalamin is a different product and its studies are not counted here.", "class_by_jurisdiction": { "US": "C", "EU": "C", "UK": null, "CA": "C", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic four-amino-acid peptide (Ala-Glu-Asp-Gly) developed in Russia as a laboratory analogue of a pineal gland extract. It is sold online as a research chemical with claims of slowing ageing and lengthening telomeres. No approved medicine contains it in any jurisdiction checked. The published research comes mostly from one group of institutes and consists of rodent lifespan studies and cultured-cell experiments; no controlled human trial of an ageing outcome was identified.", "evidence": [ { "indication": "Anti-ageing / lifespan extension", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "Lifespan and age-related tumour outcomes have been reported only in rodents, from studies by the developing research group: female mice and female rats given epitalon had changes in biomarkers of ageing, survival curves and spontaneous tumour incidence. No human study of lifespan, mortality, frailty or any clinical ageing outcome was identified. A small Russian report described night-time melatonin levels in elderly people given pineal peptides including epitalon; it measured a hormone level, not an ageing outcome, and is not counted as an efficacy trial here.", "citations": [ { "doi": "10.1023/a:1025114230714", "title": "Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice", "year": 2003, "finding": "Changes in biomarkers of ageing, survival and spontaneous tumour incidence in female SHR mice given epitalon" }, { "doi": "10.1007/s10517-007-0441-z", "title": "Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes", "year": 2007, "finding": "Effects on life span and spontaneous tumour development in female rats kept under different light regimes" }, { "pmid": 17969590, "title": "[Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people].", "year": 2007, "finding": "Night-time melatonin levels rose in old monkeys and in elderly people given pineal peptides; no ageing outcome was measured" } ], "trials_query": "epitalon" }, { "indication": "Telomere lengthening", "tier": "E7", "human_rcts": 0, "human_trials_any": 0, "summary": "The telomere claim rests on cultured-cell experiments. Epitalon added to cultured human somatic cells was reported to induce telomerase activity and telomere elongation, and a 2025 study in human cell lines reported longer telomeres through telomerase upregulation or an alternative lengthening pathway. No study measuring telomere length in people given epitalon was identified, and no study links any telomere change from epitalon to a health outcome.", "citations": [ { "doi": "10.1023/a:1025493705728", "title": "Epithalon Peptide Induces Telomerase Activity and Telomere Elongation in Human Somatic Cells", "year": 2003, "finding": "Telomerase activity and telomere elongation in cultured human somatic cells" }, { "doi": "10.1007/s10522-025-10315-x", "title": "Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity", "year": 2025, "finding": "Longer telomeres in cultured human cell lines, attributed to telomerase upregulation or alternative lengthening of telomeres" } ], "trials_query": "epitalon" } ], "safety": { "grade": "S5", "no_data_statement": true, "known_signals": [] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "No FDA-approved application: openFDA Drugs@FDA returns no application with an epitalon active ingredient (query: products.active_ingredients.name:EPITALON*; the alternative spelling EPITHALON* also returned none). openFDA states its data are unvalidated.", "source_url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:EPITALON*", "source_title": "openFDA Drugs@FDA API (FDA)", "quote": "No matches found!", "retrieved": "2026-10-10" }, { "jurisdiction": "US", "status": "unapproved", "detail": "Epitalon appears on FDA's list of bulk drug substances previously in Category 2 (significant safety risks) of the compounding interim policy whose nominations were withdrawn by the nominators. FDA's safety statement remains on the page.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026)", "quote": "Compounded drugs containing epitalon may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation and peptide-related impurities. FDA has not identified safety-related information regarding epitalon for the proposed route of administration.", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "unapproved", "detail": "No product containing epitalon (or epithalon) appears in EMA's downloadable medicines dataset (generated 10 Oct 2026), which covers centrally authorised medicines, refusals and withdrawn applications. National authorisations were not checked individually.", "source_url": "https://www.ema.europa.eu/en/medicines/download-medicine-data", "source_title": "Download medicine data | European Medicines Agency (EMA)", "quote": "This includes information on marketing authorisations of centrally authorised medicines and post-authorisation procedures.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "unapproved", "detail": "Queries of Health Canada's Drug Product Database API for the active ingredient epitalon and epithalon, and for the brand name epitalon, returned no products on the retrieval date.", "source_url": "https://health-products.canada.ca/dpd-bdpp/?lang=eng", "source_title": "Drug Product Database online query", "quote": "Search by drug identification number", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S0", "detail": "Epitalon is not named on the 2026 Prohibited List. Class S0 covers unnamed substances with no current approval by any governmental health authority; no approval was found in the jurisdictions checked, though approval elsewhere was not verified.", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "unknowns": [ "No human pharmacokinetic data by any route were identified", "No controlled human trial of any ageing, frailty or mortality outcome was identified", "No measurement of telomere length in people given epitalon was identified; the telomere findings are from cultured cells", "Rodent lifespan findings come largely from the developing group and have not been independently replicated in the studies identified", "Identity and purity of material sold as epitalon are uncontrolled; a forensic report in Drug Testing and Analysis identified epitalon in two illegal pharmaceutical preparations", "Status in the UK, Australia, Japan and China was not verified from regulator sources for this record" ], "mechanism": "The mechanism is not established. In cultured human cells epitalon was reported to increase telomerase activity, and the developing group has proposed that the peptide interacts with DNA and alters gene expression.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "follistatin-344", "names": { "inn": null, "common": [ "Follistatin-344", "Follistatin 344", "FS344", "FST344" ], "codes": [], "brands": [], "cas": null }, "sequence": null, "sequence_note": "An alternatively spliced isoform of human follistatin, a cysteine-rich secreted glycoprotein rather than a short peptide. Black-market products analysed in 2019 contained a His-tagged recombinant protein with a high proportion of oligomers.", "class_by_jurisdiction": { "US": "C", "EU": null, "UK": null, "CA": null, "AU": null, "JP": null, "CN": null }, "what_it_is": "A form of follistatin, a natural protein that binds and blocks myostatin and related growth factors that limit muscle growth. Gray-market vials labelled \"follistatin 344\" are sold for muscle building. That is different from the clinical research, which used a gene-therapy virus carrying the follistatin-344 gene, injected into the thigh muscles of a few patients with muscular dystrophy or inclusion body myositis. No follistatin product is approved as a medicine in any jurisdiction checked.", "evidence": [ { "indication": "Muscle growth and strength (injected follistatin-344 protein)", "tier": "E8", "human_rcts": 0, "human_trials_any": 0, "summary": "No published study of injected follistatin-344 protein in any model, animal or human, was identified. Animal studies of follistatin protein used other forms: an engineered follistatin-315 fusion protein increased lean mass in mice, while follistatin-288 protein in rats had mixed effects, including smaller muscles and less force in some groups. These results cannot be transferred to gray-market follistatin-344, whose stability, activity and content are unknown.", "citations": [ { "doi": "10.1124/jpet.113.211169", "title": "Follistatin: a novel therapeutic for the improvement of muscle regeneration", "year": 2014, "finding": "An engineered follistatin-315 Fc fusion protein (not follistatin-344) increased lean muscle mass in mice" }, { "doi": "10.1055/s-0042-1748535", "title": "Follistatin Protein Enhances Satellite Cell Counts in Reinnervated Muscle", "year": 2022, "finding": "Follistatin-288 protein (not follistatin-344) had mixed effects on muscle weight and force in rats after nerve injury" } ], "trials_query": "follistatin" }, { "indication": "Muscle disease via follistatin-344 gene therapy (a different intervention)", "tier": "E4", "human_rcts": 0, "human_trials_any": 2, "summary": "Gene therapy is not the gray-market product. An adeno-associated virus carrying the follistatin-344 gene was injected into the thigh muscles of six men with Becker muscular dystrophy and, separately, six people with sporadic inclusion body myositis. Walking distance improved in four of six in each study, with no adverse effects reported; the myositis study compared against eight untreated patients, not a randomised control. In macaques, the same vector increased muscle size and strength.", "citations": [ { "doi": "10.1038/mt.2014.200", "title": "A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy", "year": 2015, "finding": "Uncontrolled trial in six patients with Becker muscular dystrophy; four improved on the six-minute walk test" }, { "doi": "10.1016/j.ymthe.2017.02.015", "title": "Follistatin Gene Therapy for Sporadic Inclusion Body Myositis Improves Functional Outcomes", "year": 2017, "finding": "Six treated patients with inclusion body myositis compared with eight untreated matched patients on six-minute walk distance" }, { "doi": "10.1126/scitranslmed.3000112", "title": "Follistatin gene delivery enhances muscle growth and strength in nonhuman primates", "year": 2009, "finding": "Increased quadriceps size and strength in cynomolgus macaques after intramuscular AAV1-FS344 gene transfer" } ], "trials_query": "follistatin" } ], "safety": { "grade": "S5", "no_data_statement": true, "known_signals": [ { "signal": "Mislabelled and uncharacterised black-market products", "evidence": "In an anti-doping laboratory analysis of 17 black-market products sold as follistatin, only nine contained follistatin; some others contained different growth-promoting peptides. All nine follistatin-containing products held a His-tagged recombinant protein with a high degree of oligomers.", "citation": { "doi": "10.1002/dta.2741", "title": "Detection of black market follistatin 344" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "No FDA-approved follistatin product was identified; the black-market analysis cited above also states that no approved pharmaceutical formulations of follistatin are available. Follistatin does not appear in any category (1, 2 or 3) of FDA's list of bulk drug substances nominated for 503A compounding, updated 14 May 2026, so it has not been nominated for pharmacy compounding.", "source_url": "https://www.fda.gov/media/94155/download", "source_title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (Updated May 14, 2026)", "quote": "Includes three categories of bulk drug substances: Category 1: Bulk Drug Substances Under Evaluation Category 2: Bulk Drug Substances that Raise Significant Safety Concerns Category 3: Bulk Drug Substances Nominated Without Adequate Support", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S4.3", "detail": "Named as a myostatin-binding protein under class S4.3 (agents preventing activin receptor IIB activation), prohibited at all times, on the 2026 Prohibited List.", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Myostatin inhibitors such as: Agents reducing or ablating myostatin expression Myostatin-binding proteins (e.g. follistatin, myostatin propeptide)" }, "trials": [ { "nct": "NCT01519349", "title": "Follistatin Gene Transfer to Patients With Becker Muscular Dystrophy and Sporadic Inclusion Body Myositis", "phase": "1", "status": "Completed" }, { "nct": "NCT02354781", "title": "Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 Trial to Patients With Duchenne Muscular Dystrophy", "phase": "1/2", "status": "Completed" } ], "unknowns": [ "No human or animal study of injected follistatin-344 protein was identified, for efficacy, pharmacokinetics or safety", "Whether injected recombinant follistatin-344 protein stays active long enough in the body to affect muscle is unknown", "Follistatin also binds activins, which act in reproductive and other tissues; effects of systemic exposure in humans are unstudied", "Immunogenicity of His-tagged, partly oligomerised black-market protein has not been assessed", "The gene-therapy findings come from 12 patients without randomised controls and do not apply to protein injections", "Regulatory status outside the US was not verified from regulator sources for this record" ], "mechanism": "Follistatin binds myostatin and activins and blocks their signalling through activin type II receptors; in mice and macaques, raising follistatin levels by gene transfer increased skeletal muscle size.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "ghk-cu", "names": { "inn": null, "common": [ "GHK-Cu", "Copper peptide GHK-Cu", "Copper tripeptide", "Glycyl-L-histidyl-L-lysine copper(II)" ], "codes": [], "brands": [], "cas": null }, "sequence": "GHK", "sequence_note": "Copper(II) complex of the tripeptide glycyl-L-histidyl-L-lysine (GHK). The peptide occurs naturally in human plasma.", "class_by_jurisdiction": { "US": "C", "EU": null, "UK": null, "CA": null, "AU": null, "JP": null, "CN": null }, "what_it_is": "A copper complex of a three-amino-acid peptide found naturally in human plasma. It is a common ingredient in topical cosmetic skin products and is also sold on the gray market as an injectable with anti-ageing and tissue-healing claims. A topical gel was tested for diabetic foot ulcers in the 1990s; no approval of it was identified. It is not an FDA-approved medicine, and in the US FDA treats injectable and non-injectable use separately for compounding.", "evidence": [ { "indication": "Diabetic foot ulcers (topical gel)", "tier": "E3", "human_rcts": 1, "human_trials_any": 1, "summary": "A multicentre, randomised, evaluator-blinded, vehicle-controlled trial of a GHK-copper gel (Iamin Gel) in diabetic neuropathic plantar ulcers, published in 1994, reported greater median ulcer closure and fewer infections than vehicle when added to standard wound care. The number of participants was not stated in the abstract reviewed. No confirmatory trial was identified, and no approval of the gel was found.", "citations": [ { "doi": "10.1046/j.1524-475x.1994.20406.x", "title": "Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper", "year": 1994, "finding": "Greater median plantar ulcer closure and lower infection incidence than vehicle in a randomised, evaluator-blinded trial in patients with diabetes" } ], "trials_query": "GHK-Cu" }, { "indication": "Skin ageing, wrinkles and post-procedure skin (topical cosmetic)", "tier": "E3", "human_rcts": 1, "human_trials_any": 1, "summary": "Topical GHK-Cu is widely used in cosmetics, but controlled clinical data are sparse. In a small randomised study of 13 patients after carbon-dioxide laser resurfacing around the mouth, skin products with GHK-Cu did not reduce redness or improve blinded ratings of wrinkles or skin quality compared with products without it; only patient-reported satisfaction differed. Other published cosmetic studies mostly test multi-ingredient products, so the contribution of GHK-Cu cannot be isolated.", "citations": [ { "doi": "10.1001/archfaci.8.4.252", "title": "Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin", "year": 2006, "finding": "No difference in erythema, wrinkles or blinded skin-quality ratings versus control regimen in 13 patients; higher patient-reported satisfaction" } ], "trials_query": "GHK-Cu" }, { "indication": "Injected GHK-Cu for tissue healing, inflammation or anti-ageing", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "No human study of injected GHK-Cu has been published. In rats, injections into the knee joint after ligament reconstruction improved knee laxity and graft stiffness at 6 weeks but not at 12 weeks. In mice with chemically induced colitis, GHK-Cu reduced inflammatory markers and colon damage. FDA states that there are limited data in humans to inform safety for injectable use.", "citations": [ { "doi": "10.1002/jor.22831", "title": "Tripeptide-copper complex GHK-Cu (II) transiently improved healing outcome in a rat model of ACL reconstruction", "year": 2015, "finding": "Smaller knee laxity difference at 6 weeks but no difference at 12 weeks after ACL reconstruction in rats" }, { "doi": "10.3389/fphar.2025.1551843", "title": "Exploring the beneficial effects of GHK-Cu on an experimental model of colitis and the underlying mechanisms", "year": 2025, "finding": "Lower disease-activity scores and inflammatory cytokines in mice with DSS-induced colitis" } ], "trials_query": "GHK-Cu" } ], "safety": { "grade": "S3", "no_data_statement": false, "known_signals": [ { "signal": "Regulator-identified risk for injectable use", "evidence": "FDA lists GHK-Cu for injectable routes among substances previously in 503A Category 2 whose nominations were withdrawn, citing immunogenicity risk from aggregation and peptide-related impurities and limited human data. This is a stated risk, not a documented case of harm.", "citation": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "503a_category_1", "detail": "Not FDA-approved. For non-injectable routes only, GHK-Cu is in 503A Category 1 (under evaluation) on FDA's list updated 14 May 2026. It had been removed from Category 1 on 22 April 2026 after nominations were withdrawn, and was restored after one nominator clarified that it had withdrawn only the injectable route. FDA states it intends to consult the Pharmacy Compounding Advisory Committee before the end of February 2027.", "source_url": "https://www.fda.gov/media/94155/download", "source_title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (Updated May 14, 2026)", "quote": "GHK-Cu (except for injectable routes of administration) will be added back to category 1.", "retrieved": "2026-10-10" }, { "jurisdiction": "US", "status": "unapproved", "detail": "For injectable routes, GHK-Cu appears on FDA's list of substances nominated but withdrawn (previously in 503A Category 2), with FDA's stated risks. Page content current as of 22 April 2026.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "quote": "Compounded injectable drugs containing GHK-Cu may pose risk for immunogenicity due to the potential for aggregation and peptide-related impurities. There are limited data in humans to inform safety-related considerations.", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S0", "detail": "GHK-Cu is not named on the 2026 Prohibited List. As a pharmacological substance with no current regulatory approval for human therapeutic use, it falls within the general definition of class S0; how WADA treats its presence in topical cosmetic products was not verified:", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "trials": [ { "nct": "NCT07437586", "title": "Topical GHK-Cu Gel for Acute Skin Wound Healing", "phase": "2", "status": "Recruiting" } ], "unknowns": [ "No published human study of injected GHK-Cu, for efficacy, pharmacokinetics or safety", "How much topically applied GHK-Cu penetrates intact human skin is not established", "The 1994 diabetic ulcer trial has not been independently replicated, and its full participant numbers were not verified for this record", "Whether injected GHK-Cu alters copper balance or copper-related toxicity in humans has not been studied", "Purity, copper content and aggregation of gray-market injectable products are uncharacterised; FDA cites aggregation and impurities as an immunogenicity concern", "Regulatory status outside the US, including cosmetic-ingredient rules, was not verified from regulator sources for this record" ], "mechanism": "GHK forms a complex with copper(II) ions. In mice with chemically induced colitis GHK-Cu lowered inflammatory cytokines and increased SIRT1 protein expression; its molecular targets in human tissue are not established.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "ghrp-6", "names": { "inn": null, "common": [ "GHRP-6", "Growth hormone-releasing peptide-6", "Growth hormone releasing hexapeptide" ], "codes": [ "GHRP-6" ], "brands": [], "cas": null }, "sequence": null, "sequence_note": "Synthetic hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2; contains D-amino acids and a C-terminal amide, so no standard one-letter sequence is given.", "class_by_jurisdiction": { "US": "C", "EU": "C", "UK": null, "CA": "C", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic six-amino-acid peptide, one of the first growth hormone secretagogues, which acts on the ghrelin receptor to release growth hormone from the pituitary. It was studied widely in human endocrine physiology experiments in the 1990s but was never approved as a medicine in any jurisdiction checked. It is sold online as a research chemical with claims of raising growth hormone, appetite and muscle mass. A Cuban research centre has tested it with epidermal growth factor in acute stroke.", "evidence": [ { "indication": "Growth hormone release", "tier": "E3", "human_rcts": null, "human_trials_any": null, "summary": "Many small, short human pharmacology studies, several of them randomised placebo-controlled crossover designs in healthy volunteers or patients, show that intravenous GHRP-6 acutely raises blood growth hormone, an effect that is greater when combined with GHRH and partly depends on endogenous GHRH. It also raised ACTH and cortisol. These studies measured hormone levels over hours; none tested sustained IGF-I, body composition, strength or any clinical outcome. The number of such studies was not counted, so both counts are left blank.", "citations": [ { "doi": "10.1210/jcem-70-4-975", "title": "Growth Hormone (GH)-Releasing Peptide Stimulates GH Release in Normal Men and Acts Synergistically with GH-Releasing Hormone", "year": 1990, "finding": "Acute growth hormone release in healthy men, synergistic with GHRH" }, { "doi": "10.1210/jcem.83.4.4711", "title": "Growth Hormone (GH)-Releasing Peptide-6 Requires Endogenous Hypothalamic GH-Releasing Hormone for Maximal GH Stimulation", "year": 1998, "finding": "Maximal growth hormone response to GHRP-6 in humans required endogenous hypothalamic GHRH" }, { "doi": "10.1159/000126883", "title": "Growth Hormone-Releasing Peptide-6 Stimulates Sleep, Growth Hormone, ACTH and Cortisol Release in Normal Man", "year": 1995, "finding": "Overnight growth hormone, ACTH and cortisol rose and stage 2 sleep increased in healthy men compared with placebo" } ], "trials_query": "GHRP-6" }, { "indication": "Acute ischaemic stroke (with epidermal growth factor)", "tier": "E3", "human_rcts": null, "human_trials_any": null, "summary": "The COURAGE-2 phase III trial in Cuba randomised 188 patients with acute ischaemic stroke to intravenous epidermal growth factor plus GHRP-6 or standard care, open-label. It missed its primary endpoint: no difference in disability (modified Rankin Scale), Barthel index or survival in the whole population. Subgroup analyses suggested benefit in severe stroke, which is hypothesis-generating only. The trial tested a combination given in hospital, so it does not isolate GHRP-6 and does not bear on self-administered use.", "citations": [ { "doi": "10.1016/j.jocn.2026.112195", "title": "Phase III Open-Label, Randomized Clinical Trial of Epidermal Growth Factor and Growth Hormone Releasing Hexapeptide in Acute Ischemic Stroke", "year": 2026, "finding": "No difference in disability, Barthel index or survival with EGF plus GHRP-6 versus standard care in patients with acute ischaemic stroke; primary endpoint missed" } ], "trials_query": "growth hormone releasing peptide 6" } ], "safety": { "grade": "S3", "no_data_statement": false, "known_signals": [ { "signal": "Acute rise in ACTH and cortisol", "evidence": "In healthy men, repeated intravenous GHRP-6 raised overnight ACTH and cortisol compared with placebo.", "citation": { "doi": "10.1159/000126883", "title": "Growth Hormone-Releasing Peptide-6 Stimulates Sleep, Growth Hormone, ACTH and Cortisol Release in Normal Man" } }, { "signal": "Cortisol effects and reduced insulin sensitivity", "evidence": "FDA's compounding safety summary states that the limited available data reveal concerns including effects on cortisol and increased blood glucose from decreased insulin sensitivity.", "citation": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks" } }, { "signal": "Serious adverse events in a stroke trial, not attributed to treatment", "evidence": "In COURAGE-2, serious adverse events occurred in 30 of 95 patients given EGF plus GHRP-6 and 18 of 93 on standard care; investigators judged none treatment-related.", "citation": { "doi": "10.1016/j.jocn.2026.112195", "title": "Phase III Open-Label, Randomized Clinical Trial of Epidermal Growth Factor and Growth Hormone Releasing Hexapeptide in Acute Ischemic Stroke" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "No FDA-approved application: openFDA Drugs@FDA returns no application with a GHRP active ingredient (query: products.active_ingredients.name:GHRP*; a query for \"GROWTH HORMONE RELEASING PEPTIDE\" also returned none). openFDA states its data are unvalidated.", "source_url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:GHRP*", "source_title": "openFDA Drugs@FDA API (FDA)", "quote": "No matches found!", "retrieved": "2026-10-10" }, { "jurisdiction": "US", "status": "unapproved", "detail": "Placed in Category 2 (significant safety risks) of FDA's 503B outsourcing-facility interim policy on 29 September 2023, and listed there.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026)", "quote": "FDA has identified limited safety-related information, but the available data reveal safety concerns including potential effect on cortisol and increase in blood glucose due to decreases in insulin sensitivity.", "retrieved": "2026-10-10" }, { "jurisdiction": "US", "status": "unapproved", "detail": "For 503A pharmacy compounding, GHRP-6 is listed in Category 3 (nominated without adequate support) of FDA's bulk drug substances nomination list updated 14 May 2026; it is not on the 503A bulks list.", "source_url": "https://www.fda.gov/media/94155/download", "source_title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (Updated May 14, 2026)", "quote": "503A Category 3: Bulk Drug Substances Nominated Without Adequate Support", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "unapproved", "detail": "No product containing GHRP-6 or a growth hormone-releasing peptide appears in EMA's downloadable medicines dataset (generated 10 Oct 2026), which covers centrally authorised medicines, refusals and withdrawn applications. National authorisations were not checked individually.", "source_url": "https://www.ema.europa.eu/en/medicines/download-medicine-data", "source_title": "Download medicine data | European Medicines Agency (EMA)", "quote": "This includes information on marketing authorisations of centrally authorised medicines and post-authorisation procedures.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "unapproved", "detail": "Queries of Health Canada's Drug Product Database API for the active ingredients GHRP and growth hormone releasing peptide returned no products on the retrieval date.", "source_url": "https://health-products.canada.ca/dpd-bdpp/?lang=eng", "source_title": "Drug Product Database online query", "quote": "Search by drug identification number", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S2.2.4", "detail": "Named under S2.2.4 growth hormone releasing factors, prohibited at all times.", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "GH-releasing peptides (GHRPs) [e.g. alexamorelin, examorelin (hexarelin), GHRP-1, GHRP-2 (pralmorelin), GHRP-3, GHRP-4, GHRP-5 and GHRP-6]" }, "unknowns": [ "No human study of muscle mass, strength or body composition with GHRP-6 was identified", "No human data on repeated use over weeks or months outside hospital were identified; most human exposure is single sessions lasting hours", "Whether the growth hormone response persists or attenuates with continued use was not established for GHRP-6 in the sources reviewed (it attenuated partly with the related peptide hexarelin)", "Effects of repeated rises in cortisol and of reduced insulin sensitivity over time are unstudied", "Australian status was not verified from the TGA register; GHRP-6 is named in Schedule 4 and Appendix D of the Poisons Standard (October 2026, F2026L01327), which controls supply but is not a product approval", "Status in the UK, Japan and China was not verified from regulator sources for this record" ], "mechanism": "GHRP-6 is an agonist of the growth hormone secretagogue receptor (the ghrelin receptor); in human studies it acutely increased growth hormone secretion and also raised ACTH and cortisol.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "hexarelin", "names": { "inn": null, "common": [ "Hexarelin", "Examorelin" ], "codes": [], "brands": [], "cas": null }, "sequence": null, "sequence_note": "Synthetic hexapeptide His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2, an analogue of GHRP-6 with a methylated D-tryptophan; contains D-amino acids and a C-terminal amide, so no standard one-letter sequence is given.", "class_by_jurisdiction": { "US": "C", "EU": "C", "UK": null, "CA": "C", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic six-amino-acid growth hormone secretagogue, a close analogue of GHRP-6, that acts on the ghrelin receptor to release growth hormone. It was studied in human endocrine experiments and small clinical studies in the 1990s, including in children with short stature and in adults over 16 weeks, but was never approved as a medicine in any jurisdiction checked. WADA lists it under the name examorelin. It is sold online as a research chemical with claims of raising growth hormone and muscle mass.", "evidence": [ { "indication": "Growth hormone release", "tier": "E3", "human_rcts": null, "human_trials_any": null, "summary": "Numerous small human pharmacology studies, many randomised and placebo-controlled with crossover designs, show that hexarelin acutely raises blood growth hormone after intravenous, subcutaneous, intranasal or oral administration, alongside rises in prolactin, ACTH and cortisol. In adults given hexarelin twice daily for 16 weeks the growth hormone response was partly and reversibly attenuated, and IGF-I did not change significantly. The number of such studies was not counted, so both counts are left blank.", "citations": [ { "doi": "10.1210/jcem.78.3.8126144", "title": "Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man.", "year": 1994, "finding": "Acute growth hormone release in humans after intravenous, subcutaneous, intranasal and oral administration" }, { "doi": "10.1210/jcem.81.12.8954038", "title": "Hexarelin-induced growth hormone, cortisol, and prolactin release: a dose-response study.", "year": 1996, "finding": "Dose-dependent growth hormone, prolactin and cortisol release after intravenous hexarelin in healthy adult men" }, { "doi": "10.1210/jcem.83.5.4812", "title": "Growth Hormone Status during Long-Term Hexarelin Therapy", "year": 1998, "finding": "Partial, reversible attenuation of the growth hormone response over 16 weeks in adults, with no significant change in IGF-I" } ], "trials_query": "hexarelin" }, { "indication": "Muscle mass and body composition", "tier": "E4", "human_rcts": null, "human_trials_any": null, "summary": "The only adult study identified that measured body composition was an uncontrolled 16-week study: total body fat, lean body mass and bone mineral density did not change significantly from baseline. No randomised trial of muscle mass, strength or body composition was identified.", "citations": [ { "doi": "10.1210/jcem.83.5.4812", "title": "Growth Hormone Status during Long-Term Hexarelin Therapy", "year": 1998, "finding": "No significant change in total body fat, lean body mass or bone mineral density after 16 weeks in adults" } ], "trials_query": "hexarelin" }, { "indication": "Short stature in children", "tier": "E4", "human_rcts": null, "human_trials_any": null, "summary": "An uncontrolled study gave intranasal hexarelin to 8 prepubertal children with short stature for up to 8 months and reported higher IGF-I and faster growth velocity than before treatment. There was no control group, and no adult-height outcome was reported. Hexarelin did not proceed to approval for this use.", "citations": [ { "doi": "10.1111/j.1365-2265.1995.tb02929.x", "title": "Intranasal administration of the GHRP hexarelin accelerates growth in short children", "year": 1995, "finding": "IGF-I and growth velocity rose from baseline in 8 short prepubertal children in an uncontrolled study" } ], "trials_query": "hexarelin" } ], "safety": { "grade": "S3", "no_data_statement": false, "known_signals": [ { "signal": "Acute rise in prolactin and cortisol", "evidence": "Intravenous hexarelin raised serum prolactin and cortisol in a dose-dependent manner in healthy adult men.", "citation": { "doi": "10.1210/jcem.81.12.8954038", "title": "Hexarelin-induced growth hormone, cortisol, and prolactin release: a dose-response study." } }, { "signal": "Change in pituitary-adrenal response with repeated use", "evidence": "After 16 weeks of twice-daily subcutaneous hexarelin in adults the cortisol response to an injection was reduced, returning to baseline 4 weeks after stopping.", "citation": { "doi": "10.1046/j.1365-2265.1999.00609.x", "title": "The effect of chronic hexarelin administration on the pituitary–adrenal axis and prolactin" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "No FDA-approved application: openFDA Drugs@FDA returns no application with a hexarelin active ingredient (query: products.active_ingredients.name:HEXARELIN*; EXAMORELIN* also returned none). Hexarelin does not appear in Category 1, 2 or 3 of FDA's 503A bulk drug substances nomination list (updated 14 May 2026). openFDA states its data are unvalidated.", "source_url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:HEXARELIN*", "source_title": "openFDA Drugs@FDA API (FDA)", "quote": "No matches found!", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "unapproved", "detail": "No product containing hexarelin or examorelin appears in EMA's downloadable medicines dataset (generated 10 Oct 2026), which covers centrally authorised medicines, refusals and withdrawn applications. National authorisations were not checked individually.", "source_url": "https://www.ema.europa.eu/en/medicines/download-medicine-data", "source_title": "Download medicine data | European Medicines Agency (EMA)", "quote": "This includes information on marketing authorisations of centrally authorised medicines and post-authorisation procedures.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "unapproved", "detail": "Queries of Health Canada's Drug Product Database API for the active ingredients hexarelin and examorelin, and for the brand name hexarelin, returned no products on the retrieval date.", "source_url": "https://health-products.canada.ca/dpd-bdpp/?lang=eng", "source_title": "Drug Product Database online query", "quote": "Search by drug identification number", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S2.2.4", "detail": "Named, as examorelin (hexarelin), under S2.2.4 growth hormone releasing factors, prohibited at all times.", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "GH-releasing peptides (GHRPs) [e.g. alexamorelin, examorelin (hexarelin), GHRP-1, GHRP-2 (pralmorelin), GHRP-3, GHRP-4, GHRP-5 and GHRP-6]" }, "unknowns": [ "No randomised trial of muscle mass, strength or body composition was identified; the one uncontrolled adult study found no significant change", "Human exposure beyond about 8 months was not identified; long-term effects of repeated prolactin and cortisol rises are unstudied", "Cardiovascular effects in humans are described only in short studies; effects of long-term use on the heart are unknown", "Australian status was not verified from the TGA register; hexarelin is named in Schedule 4 and Appendix D of the Poisons Standard (October 2026, F2026L01327), which controls supply but is not a product approval", "Status in the UK, Japan and China was not verified from regulator sources for this record" ], "mechanism": "Hexarelin is an agonist of the growth hormone secretagogue receptor (the ghrelin receptor); in human studies it acutely increased growth hormone, prolactin, ACTH and cortisol secretion.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "icatibant", "names": { "inn": "icatibant", "common": [ "Icatibant", "Icatibant acetate", "HOE 140" ], "codes": [ "HOE 140" ], "brands": [ "Firazyr" ], "cas": null }, "sequence": null, "sequence_note": "Synthetic decapeptide: D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg, containing five non-proteinogenic or D-amino acids (hydroxyproline, beta-(2-thienyl)alanine, D-tetrahydroisoquinoline-3-carboxylic acid, octahydroindole-2-carboxylic acid); no standard one-letter sequence is given.", "class_by_jurisdiction": { "US": "A", "EU": "A", "UK": null, "CA": "A", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic ten-residue peptide that blocks the bradykinin B2 receptor. It is an approved prescription drug, given as a single-use prefilled syringe, for treating acute attacks of hereditary angioedema caused by C1-esterase-inhibitor deficiency. Generic versions are approved in the United States. It has also been studied, without approval, for angioedema caused by ACE-inhibitor drugs.", "evidence": [ { "indication": "Acute attacks of hereditary angioedema (C1-inhibitor deficiency)", "tier": "E1", "human_rcts": 3, "human_trials_any": 3, "summary": "Three randomised, double-blind phase 3 trials were run. FAST-1 (placebo comparator) did not meet its primary endpoint; FAST-2 (tranexamic acid comparator) did; both were reported together. FAST-3, a larger placebo-controlled trial, reported shorter time to symptom relief with icatibant. Results are consistent in direction but FAST-1 was negative on its primary endpoint, which is stated here rather than omitted.", "citations": [ { "doi": "10.1056/NEJMoa0906393", "title": "Icatibant, a New Bradykinin-Receptor Antagonist, in Hereditary Angioedema", "year": 2010, "finding": "Report of FAST-1 (versus placebo, primary endpoint not met) and FAST-2 (versus tranexamic acid, shorter time to symptom relief with icatibant) in acute hereditary angioedema attacks" }, { "doi": "10.1016/j.anai.2011.08.015", "title": "Randomized placebo-controlled trial of the bradykinin B2 receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial", "year": 2011, "finding": "Shorter time to 50% symptom reduction with icatibant than placebo in acute cutaneous and abdominal hereditary angioedema attacks" } ], "trials_query": "icatibant hereditary angioedema" }, { "indication": "ACE-inhibitor-induced angioedema (off-label)", "tier": "E3", "human_rcts": 2, "human_trials_any": 2, "summary": "Results conflict. A small randomised phase 2 trial (27 participants) compared icatibant with glucocorticoid plus antihistamine and reported faster resolution of swelling. A larger randomised, placebo-controlled phase 3 trial in emergency departments found no difference from placebo in time to meeting discharge criteria. The indication is not approved.", "citations": [ { "doi": "10.1056/nejmoa1312524", "title": "A Randomized Trial of Icatibant in ACE-Inhibitor–Induced Angioedema", "year": 2015, "finding": "Shorter time to complete resolution of oedema with icatibant than with glucocorticoid plus antihistamine in a small randomised trial" }, { "doi": "10.1016/j.jaip.2017.03.003", "title": "Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor–Induced Upper Airway Angioedema", "year": 2017, "finding": "No difference between icatibant and placebo in time to meeting discharge criteria in ACE-inhibitor-induced upper airway angioedema" } ], "trials_query": "icatibant ACE inhibitor angioedema" } ], "safety": { "grade": "S1", "no_data_statement": false, "known_signals": [ { "signal": "Injection-site reactions", "evidence": "Local injection-site reactions (erythema, swelling, pain) were the most commonly reported adverse events in the placebo-controlled FAST-3 trial.", "citation": { "doi": "10.1016/j.anai.2011.08.015", "title": "Randomized placebo-controlled trial of the bradykinin B2 receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "approved", "detail": "Firazyr (NDA 022150, Takeda Pharms USA) is listed in Drugs@FDA as a new molecular entity with priority review and orphan status, approved 25 August 2011; marketing status Prescription.", "source_url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022150", "source_title": "Drugs@FDA: FDA-Approved Drugs - NDA 022150 (Firazyr)", "quote": "08/25/2011 ORIG-1 Approval Type 1 - New Molecular Entity PRIORITY; Orphan", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "approved", "detail": "Firazyr (EMEA/H/C/000899, Takeda) is centrally authorised; marketing authorisation issued 11 July 2008. EMA overview states use in adults, adolescents and children aged over 2 years.", "source_url": "https://www.ema.europa.eu/en/medicines/human/EPAR/firazyr", "source_title": "Firazyr | European Medicines Agency (EMA)", "quote": "Firazyr is a medicine used to treat the symptoms of attacks of hereditary angioedema in adults, adolescents and children aged over 2 years.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "approved", "detail": "Health Canada Drug Product Database lists Firazyr (Takeda Canada Inc) with current status Marketed.", "source_url": "https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=91034", "source_title": "Drug Product Database: Product information - FIRAZYR", "quote": "Current status: Marketed Current status date: 2021-07-21 Original market date: See footnote 1 2014-07-14 Product name: FIRAZYR", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "not_prohibited", "wada_class": null, "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "trials": [ { "nct": "NCT00097695", "title": "Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema", "phase": "3", "status": "Completed" }, { "nct": "NCT00500656", "title": "Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (HAE)", "phase": "3", "status": "Completed" }, { "nct": "NCT00912093", "title": "A Study of Icatibant in Patients With Acute Attacks of Hereditary Angioedema (FAST-3)", "phase": "3", "status": "Completed" }, { "nct": "NCT01154361", "title": "AMelioration of Angiotensin Converting Enzyme Inhibitor Induced Angioedema Study", "phase": "2", "status": "Completed" }, { "nct": "NCT01919801", "title": "Blinded Safety & Efficacy Placebo Controlled Study of Icatibant for Angiotensin Converting Enzyme Inhibitor Induced Angioedema", "phase": "3", "status": "Completed" } ], "unknowns": [ "Whether icatibant shortens ACE-inhibitor-induced angioedema is unresolved: a small positive phase 2 trial and a larger negative phase 3 trial conflict", "No randomised evidence is cited for use as short-term prophylaxis before procedures", "Efficacy in non-hereditary forms of bradykinin-mediated angioedema other than ACE-inhibitor-induced (e.g. acquired C1-inhibitor deficiency) rests on case reports not reviewed here", "Status in the UK, Australia, Japan and China was not verified from regulator sources for this record" ], "mechanism": "Icatibant is a selective competitive antagonist of the bradykinin B2 receptor; in hereditary angioedema, swelling is attributed to excess bradykinin acting at this receptor.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "ipamorelin", "names": { "inn": null, "common": [ "Ipamorelin", "Ipamorelin acetate" ], "codes": [], "brands": [], "cas": null }, "sequence": null, "sequence_note": "Pentapeptide Aib-His-D-2-Nal-D-Phe-Lys-NH2 (Aib, alpha-aminoisobutyric acid; D-2-Nal, D-2-naphthylalanine); contains non-standard and D-amino acids.", "class_by_jurisdiction": { "US": "C", "EU": "C", "UK": null, "CA": "C", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic five-residue peptide that stimulates growth hormone release by acting on the ghrelin (growth hormone secretagogue) receptor. It was developed by Novo Nordisk in the 1990s and later tested by Helsinn as an intravenous treatment for postoperative ileus, where its published Phase 2 trial did not meet its efficacy endpoints. It is not approved anywhere checked and has no active sponsor. It is sold as a \"research chemical\" with claims of muscle gain, fat loss, recovery, sleep and \"anti-ageing\".", "evidence": [ { "indication": "Muscle gain, fat loss, recovery, sleep and anti-ageing (gray-market claims)", "tier": "E8", "human_rcts": 0, "human_trials_any": 0, "summary": "No human study has tested any of these outcomes. Human data are limited to a pharmacokinetic study in healthy men showing a single, short-lived rise in growth hormone after intravenous infusion. In mice, ipamorelin increased body fat rather than reducing it, an effect the authors attributed to GH-independent mechanisms such as increased feeding. Raised hormone levels are a laboratory measure, not evidence of muscle gain, fat loss or any health benefit.", "citations": [ { "doi": "10.1023/a:1018955126402", "title": "Pharmacokinetic-Pharmacodynamic Modeling of Ipamorelin, a Growth Hormone Releasing Peptide, in Human Volunteers", "year": 1999, "finding": "Single episode of GH release with a terminal half-life of about 2 hours after intravenous infusion in healthy men" }, { "doi": "10.1006/bbrc.2000.4065", "title": "Growth Hormone (GH)-Independent Stimulation of Adiposity by GH Secretagogues", "year": 2001, "finding": "Increased relative body fat and fat pad weight in GH-deficient and GH-intact mice" }, { "doi": "10.1016/j.ghir.2018.05.001", "title": "Analysis of new growth promoting black market products", "year": 2018, "finding": "Product-identity finding, not efficacy: glycine-extended ipamorelin (Gly-ipamorelin) identified in black-market growth-promoting products" } ], "trials_query": "ipamorelin" }, { "indication": "Postoperative ileus", "tier": "E3", "human_rcts": 0, "human_trials_any": 2, "summary": "In a randomised, double-blind, placebo-controlled Phase 2 trial in 114 adults after bowel resection, intravenous ipamorelin did not significantly shorten time to tolerating a solid meal and showed no differences on secondary endpoints. A second, larger Phase 2 trial (NCT01280344, 320 enrolled, completed 2014) has no results posted on the registry and no publication was identified. In a rat model of postoperative ileus, intravenous ipamorelin shortened time to first bowel movement.", "citations": [ { "doi": "10.1007/s00384-014-2030-8", "title": "Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients", "year": 2014, "finding": "No significant difference from placebo in time to first tolerated meal in 114 bowel-resection patients" }, { "doi": "10.1124/jpet.108.149211", "title": "Efficacy of Ipamorelin, a Novel Ghrelin Mimetic, in a Rodent Model of Postoperative Ileus", "year": 2009, "finding": "Shortened time to first bowel movement after laparotomy and intestinal manipulation in rats" } ], "trials_query": "ipamorelin" }, { "indication": "Bone growth and bone mineral content", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "Rat studies only. Ipamorelin increased longitudinal bone growth in young rats and bone mineral content in adult female rats; in the adult rats the gain reflected larger bones, with volumetric bone density unchanged. No human bone study exists.", "citations": [ { "doi": "10.1054/ghir.1999.9998", "title": "Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats", "year": 1999, "finding": "Increased longitudinal bone growth in rats" }, { "doi": "10.1677/joe.0.1650569", "title": "The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats", "year": 2000, "finding": "Increased bone mineral content via larger bone dimensions, without change in volumetric density, in adult female rats" } ], "trials_query": "ipamorelin" } ], "safety": { "grade": "S3", "no_data_statement": true, "known_signals": [ { "signal": "Serious adverse events including death in an intravenous gastric-motility trial", "evidence": "FDA's compounding safety-risk summary states that a published study identified serious adverse events including death when ipamorelin was given intravenously for gastric motility. The published postoperative ileus trial reported treatment-emergent adverse events in 87.5% on ipamorelin versus 94.8% on placebo, in a post-surgical population; causality for individual events is not established in either source.", "citation": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks" } }, { "signal": "Immunogenicity and impurity concerns", "evidence": "FDA states compounded ipamorelin acetate may pose a risk of immunogenicity for certain routes because of aggregation or peptide-related impurities, and that its unnatural amino acids complicate characterisation.", "citation": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "Not approved: no application found in Drugs@FDA (openFDA query, retrieval date). Ipamorelin acetate was placed in Category 2 (significant safety risks) of FDA's 503B interim policy on 29 September 2023 and remains listed there. For 503A it appears on FDA's list of substances previously in Category 2 whose nominations were withdrawn by the nominators; FDA's safety statement remains on the page. FDA states it has no safety information for other injectable routes and lacks sufficient information to know whether it would cause harm.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026)", "quote": "Compounded drugs containing Ipamorelin acetate may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation or peptide-related impurities.", "retrieved": "2026-10-10" }, { "jurisdiction": "US", "status": "unapproved", "detail": "Ipamorelin does not appear in Category 1, 2 or 3 of FDA's list of bulk drug substances nominated for 503A compounding (updated 14 May 2026). It is not on the 503A bulks list and is not a component of any FDA-approved drug product.", "source_url": "https://www.fda.gov/media/94155/download", "source_title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (Updated May 14, 2026)", "quote": "Category 1: Bulk Drug Substances Under Evaluation", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "unapproved", "detail": "No product containing ipamorelin appears in EMA's downloadable medicines dataset (2,748 records, generated 10 Oct 2026), which covers centrally authorised medicines, refusals and withdrawn applications. National authorisations were not checked individually.", "source_url": "https://www.ema.europa.eu/en/medicines/download-medicine-data", "source_title": "Download medicine data | European Medicines Agency (EMA)", "quote": "This includes information on marketing authorisations of centrally authorised medicines and post-authorisation procedures.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "unapproved", "detail": "Queries of Health Canada's Drug Product Database for the active ingredient and brand name ipamorelin returned no products under any status on the retrieval date.", "source_url": "https://health-products.canada.ca/dpd-bdpp/?lang=eng", "source_title": "Drug Product Database online query", "quote": "Search by drug identification number", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S2.2.4", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "growth hormone secretagogues (GHS) and their mimetics [e.g. anamorelin, capromorelin, ibutamoren (MK-677), ipamorelin, lenomorelin (ghrelin), macimorelin and tabimorelin]" }, "trials": [ { "nct": "NCT00672074", "title": "Safety and Efficacy of Ipamorelin for Management of Post-Operative Ileus", "phase": "2", "status": "Completed" }, { "nct": "NCT01280344", "title": "Safety and Efficacy of Ipamorelin Compared to Placebo for the Recovery of Gastrointestinal Function", "phase": "2", "status": "Completed" } ], "unknowns": [ "No published human pharmacokinetic or safety data for subcutaneous use were identified in this review (published human studies used intravenous infusion); FDA states it has not identified safety-related information for certain other injectable routes", "No human data on repeated exposure beyond about a week; no long-term safety data", "Results of the larger Phase 2 ileus trial (NCT01280344, 320 enrolled) have not been posted or published", "Whether it increases body fat in humans, as it did in mice, is unknown", "Product identity: N-terminally glycine-extended ipamorelin (Gly-ipamorelin) has been identified in black-market growth-promoting products, so what a vial sold as ipamorelin contains is uncertain", "Regulatory status in the UK, Australia, Japan and China was not verified from regulator sources for this record" ], "mechanism": "Ipamorelin is an agonist at the growth hormone secretagogue (ghrelin) receptor; it released growth hormone in rats and swine, and in swine it did not raise ACTH or cortisol above levels seen with GHRH.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "kisspeptin-10", "names": { "inn": null, "common": [ "Kisspeptin-10", "KP-10", "Metastin 45-54", "Kisspeptin 112-121" ], "codes": [ "KP-10" ], "brands": [], "cas": null }, "sequence": "YNWNSFGLRF", "sequence_note": "C-terminal arginyl-phenylalanine amide (RF-NH2); the ten C-terminal residues of the kisspeptin precursor encoded by KISS1.", "class_by_jurisdiction": { "US": "C", "EU": null, "UK": null, "CA": null, "AU": null, "JP": null, "CN": null }, "what_it_is": "A ten-amino-acid peptide corresponding to the shortest naturally occurring active fragment of kisspeptin, a hypothalamic signal that drives release of gonadotropin-releasing hormone. It is used as a research tool in human reproductive-physiology studies. It is not approved as a medicine in any jurisdiction checked, and it is sold on the gray market with claims of raising testosterone and libido. The US FDA lists it among bulk substances raising significant safety risks for pharmacy compounding.", "evidence": [ { "indication": "Low testosterone / secondary hypogonadism in men", "tier": "E4", "human_rcts": null, "human_trials_any": 3, "summary": "Small, short physiology studies in healthy men and in men with type 2 diabetes and low testosterone found that intravenous kisspeptin-10 acutely raised luteinising hormone and, during infusion, testosterone. These studies measured hormone levels over hours; none tested symptoms, sexual function, body composition or any clinical outcome, and none lasted weeks or months. Whether any of the designs were randomised was not verified, so the RCT count is left blank. No trial of repeated self-administered kisspeptin-10 in hypogonadism was identified.", "citations": [ { "doi": "10.1210/jc.2011-0089", "title": "Kisspeptin-10 Is a Potent Stimulator of LH and Increases Pulse Frequency in Men", "year": 2011, "finding": "Intravenous kisspeptin-10 acutely raised LH and increased LH pulse frequency in healthy men" }, { "doi": "10.1111/cen.12103", "title": "Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: Kisspeptin‐10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism", "year": 2013, "finding": "Kisspeptin-10 infusion raised LH and serum testosterone over hours in men with type 2 diabetes and mildly low testosterone" }, { "doi": "10.1210/jc.2010-3046", "title": "Kisspeptin Resets the Hypothalamic GnRH Clock in Men", "year": 2011, "finding": "A single intravenous kisspeptin-10 bolus reset the timing of endogenous GnRH-driven LH pulses in healthy men" } ], "trials_query": "kisspeptin-10" } ], "safety": { "grade": "S4", "no_data_statement": true, "known_signals": [] }, "regulatory": [ { "jurisdiction": "US", "status": "503a_category_2", "detail": "Not approved: no FDA application exists. FDA's 503A bulk drug substances list (updated 14 May 2026) places Kisspeptin-10 in Category 2, bulk substances raising significant safety risks, added 29 September 2023. At the 29 October 2024 Pharmacy Compounding Advisory Committee meeting, reviewing use for secondary hypogonadism in men, the committee voted 0 yes, 11 no on adding it to the 503A bulks list.", "source_url": "https://www.fda.gov/media/94155/download", "source_title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (Updated May 14, 2026)", "quote": "503A Category 2: Bulk Drug Substances that Raise Significant Safety Risks", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S2.2.1", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "S2.2.1 TESTOSTERONE-STIMULATING PEPTIDES IN MALES INCLUDING, BUT NOT LIMITED TO: chorionic gonadotrophin (CG) luteinizing hormone (LH) gonadotrophin- releasing hormone (GnRH, gonadorelin) and its agonist analogues (e.g. buserelin, deslorelin, goserelin, histrelin, leuprorelin, nafarelin and triptorelin) kisspeptin and its agonist analogues" }, "trials": [ { "nct": "NCT00914823", "title": "Kisspeptin Administration in the Adult", "phase": "1", "status": "Completed" }, { "nct": "NCT03315325", "title": "Age-dependent Changes in the Responsiveness of Hypothalamic Pituitary Gonadal Axis in Men", "phase": "3", "status": "Completed" } ], "unknowns": [ "No human data on repeated or long-term kisspeptin-10 exposure; published human studies are acute, lasting hours", "No human pharmacokinetic or safety data for subcutaneous or intramuscular self-administration of gray-market material; FDA states it has no, or only limited, safety information for the proposed routes", "Immunogenicity is unassessed: FDA's compounding risk summary states injectable kisspeptin-10 may pose a risk of immunogenicity and raises peptide-impurity and characterisation concerns", "No kisspeptin-10 study of sexual desire or sexual function in humans was identified; the human brain-imaging and tumescence studies of kisspeptin and sexual processing used kisspeptin-54, a different peptide", "Whether continued exposure stimulates or instead suppresses the reproductive axis in men over time is not established for kisspeptin-10", "Regulatory status outside the US was not verified from regulator sources for this record" ], "mechanism": "Kisspeptin-10 is an agonist of the kisspeptin receptor (KISS1R, formerly GPR54) on hypothalamic GnRH neurons; in human studies intravenous kisspeptin-10 acutely increased luteinising hormone secretion.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "kpv", "names": { "inn": null, "common": [ "KPV", "Lys-Pro-Val", "Lysine-proline-valine", "alpha-MSH(11-13)" ], "codes": [], "brands": [], "cas": "67727-97-3" }, "sequence": "KPV", "sequence_note": "Tripeptide H-Lys-Pro-Val-OH, corresponding to the C-terminal residues 11-13 of alpha-melanocyte-stimulating hormone (alpha-MSH). CAS number as given for KPV (free base) in FDA's July 2026 briefing document; KPV acetate is a distinct salt form. FDA notes that different salts and derivatives are sold under the same name.", "class_by_jurisdiction": { "US": "C", "EU": null, "UK": null, "CA": null, "AU": null, "JP": null, "CN": null }, "what_it_is": "A three-amino-acid peptide (lysine-proline-valine) matching the tail end of the hormone alpha-MSH. It is sold on the gray market for gut inflammation, skin conditions and wound healing. It is not an approved medicine. FDA's 2026 briefing document states that FDA identified no clinical studies and no human exposure data for KPV by any route of administration.", "evidence": [ { "indication": "Inflammatory bowel disease and gut inflammation", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "In mice with chemically induced or immune-transfer colitis, KPV reduced inflammatory markers and tissue damage. Several later studies tested KPV in nanoparticle or hydrogel carriers in rodents. No study in people with Crohn's disease, ulcerative colitis or any other gut condition has been published, and FDA found no human data of any kind.", "citations": [ { "doi": "10.1053/j.gastro.2007.10.026", "title": "PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation", "year": 2008, "finding": "Reduced inflammatory cytokine expression in human intestinal cell lines and in mice with DSS- and TNBS-induced colitis" }, { "doi": "10.1002/ibd.20334", "title": "Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease", "year": 2008, "finding": "Less weight loss and fewer inflammatory infiltrates in two mouse models of colitis" } ], "trials_query": "KPV" }, { "indication": "Wound healing", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "Published wound data are limited to animal models; the study cited here used eye drops after corneal scraping in rabbits. No study of skin wounds, surgical wounds or chronic ulcers in humans has been published. FDA reviewed KPV for wound healing in 2026 and noted that none of the references submitted by the nominator studied KPV in humans.", "citations": [ { "doi": "10.1016/j.exer.2006.07.014", "title": "Effects of the COOH-terminal tripeptide alpha-MSH(11-13) on corneal epithelial wound healing: role of nitric oxide", "year": 2006, "finding": "Faster corneal epithelial closure after mechanical abrasion in rabbits given topical KPV, blocked by a nitric oxide synthase inhibitor" } ], "trials_query": "KPV" }, { "indication": "Inflammatory skin conditions (psoriasis, eczema)", "tier": "E7", "human_rcts": 0, "human_trials_any": 0, "summary": "Evidence is limited to cultured human skin cells and a laboratory three-dimensional skin model, where KPV reduced inflammatory signalling triggered by fine dust particles. No animal model of psoriasis or eczema treated with KPV and no human study were identified.", "citations": [ { "doi": "10.1016/j.tice.2025.102837", "title": "Lysine-Proline-Valine peptide mitigates fine dust-induced keratinocyte apoptosis and inflammation by regulating oxidative stress and modulating the MAPK/NF-κB pathway", "year": 2025, "finding": "Reduced IL-1beta secretion and cell death in cultured human keratinocytes exposed to fine particulate matter" } ], "trials_query": "KPV" } ], "safety": { "grade": "S5", "no_data_statement": true, "known_signals": [] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "No FDA-approved product. KPV was formerly in 503A Category 2 and now appears on FDA's list of substances nominated but withdrawn. FDA evaluated KPV (free base) and KPV acetate for wound healing and inflammatory conditions for the Pharmacy Compounding Advisory Committee meeting of 23 July 2026, and its briefing document recommended against adding either form to the 503A bulks list. The committee's vote and any final FDA decision were not verified from an FDA source for this record.", "source_url": "https://www.fda.gov/media/193346/download", "source_title": "July 23-24, 2026, Meeting of the Pharmacy Compounding Advisory Committee – FDA Briefing Document for KPV-Related Bulk Drug Substances (KPV (free base) and KPV acetate)", "quote": "After considering the information currently available, a balancing of the criteria weighs against KPV (free base) or KPV acetate being placed on that list", "retrieved": "2026-10-10" }, { "jurisdiction": "US", "status": "unapproved", "detail": "FDA's page on bulk drug substances that may present significant safety risks lists KPV under 'Bulk drug substances nominated but withdrawn' (substances previously in Category 2). Page content current as of 22 April 2026.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "quote": "FDA has not identified any human exposure data on drug products containing KPV administered via any route of administration.", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S0", "detail": "KPV is not named on the 2026 Prohibited List. As a pharmacological substance with no current regulatory approval for human therapeutic use, it falls within the general definition of class S0:", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "unknowns": [ "No human pharmacokinetic or pharmacodynamic data by any route; FDA identified none", "No human safety data of any kind: FDA found no clinical studies, no FAERS reports and no published case reports", "Whether KPV taken by mouth survives digestion and reaches inflamed colon tissue in humans is untested; mouse studies relied on drinking water or specialised carriers", "Which salt or derivative is present in gray-market products is unverified; FDA notes that multiple salts and derivatives, including different active moieties, are sold under the name KPV", "Immunogenicity in humans has not been assessed", "Regulatory status outside the US was not verified from regulator sources for this record" ], "mechanism": "In cell studies KPV is taken up by the PepT1 peptide transporter and reduces NF-kappaB and MAP kinase inflammatory signalling; in mice its effects on colitis appeared to be at least partly independent of the melanocortin-1 receptor.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "leuprolide", "names": { "inn": "leuprorelin", "common": [ "Leuprolide", "Leuprolide acetate", "Leuprorelin", "Leuprorelin mesilate" ], "codes": [], "brands": [ "Lupron Depot", "Lupron", "Camcevi" ], "cas": null }, "sequence": null, "sequence_note": "Synthetic GnRH agonist nonapeptide: pGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt (N-terminal pyroglutamate, D-leucine at position 6, C-terminal ethylamide); no standard one-letter sequence is given.", "class_by_jurisdiction": { "US": "A", "EU": "A", "UK": null, "CA": "A", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic nine-residue analogue of gonadotropin-releasing hormone (GnRH). After an initial surge, continued exposure suppresses pituitary gonadotropin release and lowers testosterone or oestrogen to castrate or postmenopausal levels. It is an approved prescription drug in long-acting injectable forms. Labelled uses include advanced prostate cancer, endometriosis, uterine fibroids (with iron, before surgery) and central precocious puberty, varying by product and jurisdiction.", "evidence": [ { "indication": "Advanced prostate cancer (androgen deprivation)", "tier": "E2", "human_rcts": 1, "human_trials_any": 1, "summary": "A randomised trial in metastatic prostate cancer compared leuprolide with diethylstilbestrol, the hormonal standard of the time, and reported similar disease response with fewer cardiovascular and breast adverse effects. The wider GnRH-agonist trial literature is larger than the single RCT cited here; only the verified trial is counted.", "citations": [ { "doi": "10.1056/nejm198411153112004", "title": "Leuprolide versus Diethylstilbestrol for Metastatic Prostate Cancer", "year": 1984, "finding": "Comparable response rates with leuprolide and diethylstilbestrol in men with metastatic prostate cancer, with fewer cardiovascular and breast adverse effects in the leuprolide arm" } ], "trials_query": "leuprolide prostate cancer" }, { "indication": "Endometriosis (pain)", "tier": "E2", "human_rcts": 2, "human_trials_any": 2, "summary": "A randomised, double-blind, placebo-controlled trial reported reduced endometriosis-associated pain with depot leuprolide. A 12-month randomised trial tested hormonal add-back regimens alongside leuprolide to limit bone loss and menopausal symptoms. Hypo-oestrogenic adverse effects, including bone mineral density loss, limit duration of use.", "citations": [ { "doi": "10.1016/s0015-0282(16)53755-8", "title": "Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study", "year": 1990, "finding": "Greater reduction in endometriosis symptoms with depot leuprolide than with placebo in a randomised double-blind trial" }, { "doi": "10.1016/s0029-7844(97)00620-0", "title": "Leuprolide Acetate Depot and Hormonal Add-Back in Endometriosis: A 12-Month Study", "year": 1998, "finding": "Randomised comparison of hormonal add-back regimens given with depot leuprolide in women with endometriosis, assessing pain relief and bone mineral density" } ], "trials_query": "leuprolide endometriosis" }, { "indication": "Uterine leiomyomata (fibroids), before surgery", "tier": "E3", "human_rcts": 1, "human_trials_any": 1, "summary": "A small randomised, placebo-controlled, double-blind trial reported reductions in uterine and fibroid volume with depot leuprolide. Larger trials with surgical or long-term outcomes were not verified for this record.", "citations": [ { "doi": "10.1016/s0015-0282(16)60486-7", "title": "A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide acetate depot in the treatment of uterine leiomyomata", "year": 1989, "finding": "Reduction in uterine volume with depot leuprolide compared with placebo in women with uterine leiomyomata" } ], "trials_query": "leuprolide leiomyoma" }, { "indication": "Central precocious puberty", "tier": "E4", "human_rcts": 0, "human_trials_any": 1, "summary": "Approval and current evidence in central precocious puberty rest on single-arm, open-label studies measuring suppression of the pituitary-gonadal axis, such as a recent phase 3 study of a long-acting formulation. A randomised placebo-controlled design is not used in this condition; no RCT is cited.", "citations": [ { "doi": "10.1210/jendso/bvaf224", "title": "Long-term Safety, Efficacy, and PROs: Phase 3 Study of Leuprolide Acetate 6-month IM Depot in Central Precocious Puberty", "year": 2026, "finding": "Single-arm phase 3 study reporting suppression of luteinising hormone in children with central precocious puberty" } ], "trials_query": "leuprolide precocious puberty" } ], "safety": { "grade": "S1", "no_data_statement": false, "known_signals": [ { "signal": "Diabetes and cardiovascular disease during androgen deprivation", "evidence": "In a large observational cohort of men with prostate cancer, GnRH-agonist therapy was associated with higher risk of incident diabetes, coronary heart disease, myocardial infarction and sudden cardiac death.", "citation": { "doi": "10.1200/JCO.2006.06.2497", "title": "Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy for Prostate Cancer" } }, { "signal": "Bone mineral density loss with hypo-oestrogenism", "evidence": "Bone loss during leuprolide treatment for endometriosis was the reason hormonal add-back regimens were tested in a randomised trial.", "citation": { "doi": "10.1016/s0029-7844(97)00620-0", "title": "Leuprolide Acetate Depot and Hormonal Add-Back in Endometriosis: A 12-Month Study" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "approved", "detail": "Lupron Depot (NDA 019732, AbbVie Endocrine Inc) is listed in Drugs@FDA with marketing status Prescription and original approval on 26 January 1989; further Lupron Depot strengths are under NDA 020517.", "source_url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019732", "source_title": "Drugs@FDA: FDA-Approved Drugs - NDA 019732 (Lupron Depot)", "quote": "01/26/1989 ORIG-1 Approval Type 3 - New Dosage Form PRIORITY", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "approved", "detail": "Camcevi (leuprorelin mesilate, EMEA/H/C/005034) is centrally authorised for hormone-dependent prostate cancer; marketing authorisation issued 24 May 2022. Other leuprorelin products in the EU are nationally authorised and were not individually verified.", "source_url": "https://www.ema.europa.eu/en/medicines/human/EPAR/camcevi", "source_title": "Camcevi | European Medicines Agency (EMA)", "quote": "Camcevi is indicated for the treatment of hormone dependent advanced prostate cancer and for the treatment of high-risk localised and locally advanced hormone dependent prostate cancer in combination with radiotherapy.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "approved", "detail": "Health Canada Drug Product Database lists Lupron Depot (AbbVie Corporation) with current status Marketed.", "source_url": "https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=10318", "source_title": "Drug Product Database: Product information - LUPRON DEPOT", "quote": "Current status: Marketed Current status date: 2013-12-11 Original market date: See footnote 1 1989-12-31 Product name: LUPRON DEPOT", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S2.2.1", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "S2.2.1 TESTOSTERONE-STIMULATING PEPTIDES IN MALES INCLUDING, BUT NOT LIMITED TO: chorionic gonadotrophin (CG) luteinizing hormone (LH) gonadotrophin- releasing hormone (GnRH, gonadorelin) and its agonist analogues (e.g. buserelin, deslorelin, goserelin, histrelin, leuprorelin, nafarelin and triptorelin)" }, "trials": [], "unknowns": [ "The single prostate cancer RCT cited predates modern trial registration; registered-trial denominators for leuprolide will undercount the pre-2000 evidence base", "Long-term outcomes of childhood treatment for central precocious puberty (adult height, fertility, bone health) are not established by the single-arm study cited", "Whether the cardiometabolic associations seen in observational androgen-deprivation cohorts are causal has not been established by randomised data cited here", "Status in the UK, Australia, Japan and China was not verified from regulator sources for this record" ], "mechanism": "Leuprolide is a GnRH receptor agonist; in human studies continuous exposure, after an initial rise, down-regulates pituitary GnRH receptors and suppresses luteinising hormone, follicle-stimulating hormone and sex-steroid levels.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "ll-37", "names": { "inn": null, "common": [ "LL-37", "Cathelicidin LL-37", "Human cathelicidin antimicrobial peptide", "Ropocamptide" ], "codes": [], "brands": [], "cas": null }, "sequence": "LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES", "sequence_note": "37 residues cleaved from the C-terminus of the human cathelicidin precursor hCAP-18 (UniProt P49913, residues 134-170). Ropocamptide is the name used by its developer, Promore Pharma, for a topical synthetic LL-37 product.", "class_by_jurisdiction": { "US": "C", "EU": null, "UK": null, "CA": null, "AU": null, "JP": null, "CN": null }, "what_it_is": "A 37-amino-acid antimicrobial peptide made naturally by human white blood cells and skin and mucosal cells, the only human member of the cathelicidin family. A synthetic version has been tested as a topical treatment for chronic leg and foot ulcers. Separately, it is sold on the gray market, often for injection, with claims for chronic infections, immune support and gut health. It is not approved as a medicine in any jurisdiction checked.", "evidence": [ { "indication": "Chronic venous leg ulcers unresponsive to standard care (topical synthetic LL-37)", "tier": "E3", "human_rcts": 2, "human_trials_any": 2, "summary": "A first-in-human randomised trial in 34 patients over four weeks reported faster healing-rate constants for the two lower concentrations than for placebo, but not for the highest. The larger phase 2b trial (HEAL LL-37, 148 patients, sponsored by the developer) found no significant improvement in healing compared with placebo in the full population; benefit in patients with large ulcers came from a post hoc subgroup analysis. The randomised evidence is conflicting and the larger trial was negative.", "citations": [ { "doi": "10.1111/wrr.12977", "title": "Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial", "year": 2021, "finding": "No significant difference in ulcer healing versus placebo in 148 patients with venous leg ulcers; post hoc subgroup differences only" }, { "doi": "10.1111/wrr.12211", "title": "Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial", "year": 2014, "finding": "Higher healing-rate constants than placebo at the two lower concentrations, not the highest, in 34 patients over four weeks" } ], "trials_query": "LL-37" }, { "indication": "Diabetic foot ulcers (topical synthetic LL-37)", "tier": "E3", "human_rcts": 1, "human_trials_any": 1, "summary": "One small randomised, double-blind, placebo-controlled trial in Jakarta treated mildly infected diabetic foot ulcers with LL-37 cream or placebo cream for four weeks. A granulation index increased more with LL-37; wound inflammatory cytokines and aerobic bacterial counts did not differ significantly between groups. No confirmatory trial was identified.", "citations": [ { "doi": "10.1007/s00403-023-02657-8", "title": "Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial", "year": 2023, "finding": "Greater increase in granulation index than placebo over four weeks in patients with mildly infected diabetic foot ulcers; no difference in bacterial colonisation" } ], "trials_query": "LL-37 diabetic foot ulcer" }, { "indication": "Systemic or chronic infections and immune support (injected LL-37, gray-market claims)", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "LL-37 kills a range of bacteria in laboratory assays, with activity reduced for some organisms at physiological salt concentrations. In a mouse model of polymicrobial sepsis, intravenous LL-37 improved survival and lowered bacterial counts. No human trial of injected or oral LL-37 for any infection, for immune support or for gut health was identified. The only registered human trial of injected LL-37 identified was a four-patient intratumoural melanoma study, without published results.", "citations": [ { "doi": "10.1093/intimm/dxv113", "title": "Antimicrobial cathelicidin peptide LL-37 inhibits the pyroptosis of macrophages and improves the survival of polybacterial septic mice", "year": 2016, "finding": "Intravenous LL-37 improved survival and reduced bacterial burden in mice with caecal ligation and puncture sepsis" }, { "doi": "10.1128/AAC.42.9.2206", "title": "Activities of LL-37, a Cathelin-Associated Antimicrobial Peptide of Human Neutrophils", "year": 1998, "finding": "LL-37 showed antimicrobial activity against several bacterial species in vitro; some organisms were resistant in physiological salt" } ], "trials_query": "LL-37" } ], "safety": { "grade": "S3", "no_data_statement": true, "known_signals": [] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "Not approved: FDA has approved no product containing LL-37. FDA's list of bulk substances that may present significant safety risks names cathelicidin LL-37 among substances previously in 503A Category 2 whose nominations were withdrawn; it is not on the current 503A Category 1 or 2 lists (updated 14 May 2026). FDA cites possible immunogenicity, impurity and characterisation concerns, and nonclinical findings of detrimental effects on male reproduction and protumorigenic effects in some tissues.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (FDA, content current as of 04/22/2026)", "quote": "FDA lacks sufficient safety-related information regarding cathelicidin LL-37 to know whether the drug would cause harm when administered to humans.", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S0", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "trials": [ { "nct": "NCT04098562", "title": "Efficacy of LL-37 Cream on Bacteria Colonization, Inflammation Response and Healing Rate of Diabetic Foot Ulcers", "phase": "2", "status": "Unknown" }, { "nct": "NCT02225366", "title": "Intratumoral Injections of LL37 for Melanoma", "phase": "1/2", "status": "Completed" } ], "unknowns": [ "Human safety data come only from short topical use on ulcers; there are no published human safety or pharmacokinetic data for injected, oral or nasal LL-37", "FDA cites nonclinical findings suggesting detrimental effects on male reproduction and protumorigenic effects in some tissues; their relevance to human use is not established", "Endogenous LL-37 has been implicated in inflammatory skin disease such as rosacea and psoriasis; whether supplemental LL-37 affects these conditions is untested", "Immunogenicity of injected synthetic LL-37 is unassessed", "LL-37 is not named on the 2026 WADA Prohibited List; S0 is applied here because no approval by any regulator was identified, not because WADA has classified it by name", "Regulatory status outside the US was not verified from regulator sources for this record" ], "mechanism": "LL-37 is a cationic, amphipathic peptide that disrupts bacterial membranes and binds bacterial lipopolysaccharide in vitro, and modulates inflammatory cytokine production by immune cells.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "mazdutide", "names": { "inn": "mazdutide", "common": [ "Mazdutide" ], "codes": [ "IBI362", "LY3305677" ], "brands": [ "Xinermei" ], "cas": "2259884-03-0" }, "sequence": null, "sequence_note": "Synthetic lipidated peptide; full structure not verified for this record.", "class_by_jurisdiction": { "US": "B", "EU": "B", "UK": "B", "CA": "B", "AU": "B", "JP": "B", "CN": "A" }, "what_it_is": "A synthetic peptide that activates the glucagon and GLP-1 receptors, co-developed by Innovent Biologics and Eli Lilly. A peer-reviewed drug-development review (Drugs, 2025) reports approval in China in June 2025 for long-term weight management and in September 2025 for type 2 diabetes. It is not approved in the US, EU, Canada, Australia or Japan, where it remains investigational.", "evidence": [ { "indication": "Weight reduction in obesity or overweight", "tier": "E1", "human_rcts": null, "human_trials_any": null, "summary": "GLORY-1 (phase 3, 610 Chinese adults): weight change at week 48 was -11.00% and -14.01% in the two dose groups versus +0.30% with placebo. A US phase 2 trial (179 adults, Lilly-funded) reported -7.3% to -18.1% across dose groups versus -0.9% with placebo at 32 weeks; discontinuation for adverse events reached 20% in the highest dose group.", "citations": [ { "doi": "10.1056/NEJMoa2411528", "title": "Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight", "year": 2025, "finding": "GLORY-1: weight change -11.00% and -14.01% vs +0.30% with placebo at week 48" }, { "doi": "10.1016/s2213-8587(26)00160-9", "title": "Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial", "year": 2026, "finding": "US phase 2: weight change -7.3% to -18.1% vs -0.9% with placebo at 32 weeks" } ], "trials_query": "mazdutide OR IBI362 OR LY3305677" }, { "indication": "Type 2 diabetes: glycaemic control", "tier": "E1", "human_rcts": null, "human_trials_any": null, "summary": "Two phase 3 trials in Chinese adults. Versus placebo (320 participants, 24 weeks), HbA1c fell 1.57 and 2.15 percentage points versus 0.14. Versus the approved GLP-1 receptor agonist dulaglutide (731 participants, 28 weeks), both mazdutide doses were non-inferior and superior for HbA1c (differences -0.24 and -0.30 points) with greater weight loss. Gastrointestinal adverse events were more frequent than with dulaglutide.", "citations": [ { "doi": "10.1038/s41586-025-10026-w", "title": "Mazdutide versus placebo in Chinese adults with type 2 diabetes", "year": 2025, "finding": "HbA1c change -1.57 and -2.15 vs -0.14 points with placebo at 24 weeks" }, { "doi": "10.1038/s41586-025-10031-z", "title": "Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes", "year": 2025, "finding": "HbA1c superior to dulaglutide (differences -0.24 and -0.30 points) at 28 weeks" } ], "trials_query": "mazdutide OR IBI362" } ], "safety": { "grade": "S2", "no_data_statement": true, "known_signals": [ { "signal": "Gastrointestinal adverse events", "evidence": "Diarrhoea, nausea and vomiting were the most common adverse events in phase 3 trials; incidence was higher than with dulaglutide in DREAMS-2. In the US phase 2 trial, discontinuation for adverse events reached 20% in the highest dose group, mainly gastrointestinal.", "citation": { "doi": "10.1038/s41586-025-10031-z", "title": "Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "investigational", "detail": "No Drugs@FDA application found for mazdutide (openFDA Drugs@FDA query by active ingredient returns no records). Lilly-sponsored phase 2 trials are registered on ClinicalTrials.gov.", "source_url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:mazdutide", "source_title": "openFDA Drugs@FDA API query: active ingredient mazdutide", "quote": "\"code\": \"NOT_FOUND\", \"message\": \"No matches found!\"", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "investigational", "detail": "Mazdutide does not appear in the EMA medicines dataset (2,748 records of centrally processed medicines, timestamp 2026-10-10).", "source_url": "https://www.ema.europa.eu/en/documents/report/medicines-output-medicines_json-report_en.json", "source_title": "EMA medicines data (JSON report)", "quote": "\"total_records\": 2748, \"timestamp\": \"2026-10-10T06:02:36Z\"", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "investigational", "detail": "Health Canada Drug Product Database active-ingredient query for mazdutide returns an empty result.", "source_url": "https://health-products.canada.ca/api/drug/activeingredient/?lang=en&type=json&ingredientname=mazdutide", "source_title": "Health Canada Drug Product Database API: active ingredient mazdutide", "quote": "[]", "retrieved": "2026-10-10" }, { "jurisdiction": "AU", "status": "investigational", "detail": "TGA Product Information repository search for mazdutide returns no documents.", "source_url": "https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=PI&q=mazdutide", "source_title": "TGA eBS - Product and Consumer Medicine Information (search: mazdutide)", "quote": "Search PI Trade Names and Active Ingredients containing mazdutide . 0 Documents available.", "retrieved": "2026-10-10" }, { "jurisdiction": "JP", "status": "investigational", "detail": "Mazdutide does not appear in the PMDA List of Approved Products (New Drugs), which covers approvals through February 2026.", "source_url": "https://www.pmda.go.jp/files/000281190.pdf", "source_title": "PMDA List of Approved Products: New Drugs (April 2004 to February 2026)", "quote": "April 2004 to February 2026", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "not_prohibited", "wada_class": null, "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development" }, "trials": [ { "nct": "NCT05607680", "title": "A Study of IBI362 in Participants With Obesity or Overweight", "phase": "3", "status": "Completed" }, { "nct": "NCT05628311", "title": "A Study of IBI362 in Poorly Controlled Type 2 Diabetes Patients Only Through Diet and Exercise", "phase": "3", "status": "Completed" }, { "nct": "NCT05606913", "title": "A Study of IBI362 in Participants With Type 2 Diabetes", "phase": "3", "status": "Completed" }, { "nct": "NCT06184568", "title": "A Study Comparing IBI362 vs Semaglutide in Chinese Adults With Early Type 2 Diabetes and Obesity", "phase": "3", "status": "Completed" }, { "nct": "NCT06124807", "title": "A Study of LY3305677 Compared With Placebo in Adult Participants With Obesity or Overweight", "phase": "2", "status": "Completed" }, { "nct": "NCT06817356", "title": "A Study to Evaluate Mazdutide Compared With Placebo in Participants With Alcohol Use Disorder", "phase": "2", "status": "Completed" } ], "unknowns": [ "Cardiovascular outcomes; no cardiovascular outcome trial was located on ClinicalTrials.gov or in publications", "Efficacy and safety in non-Chinese populations beyond a single 179-participant US phase 2 trial", "Safety beyond 48 weeks of exposure, the longest duration in the published phase 3 trials", "Post-marketing safety experience in China since 2025; no surveillance data were located", "Exact wording and scope of the China approvals as issued by the NMPA, which could not be read for this record" ], "mechanism": "Mazdutide is a peptide agonist of both the glucagon receptor and the GLP-1 receptor.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "melanotan-ii", "names": { "inn": null, "common": [ "Melanotan II", "Melanotan-II", "MT-II", "Melanotan 2" ], "codes": [ "MT-II" ], "brands": [], "cas": null }, "sequence": null, "sequence_note": "Lactam-bridged cyclic heptapeptide analogue of alpha-MSH(4-10): Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, as described by Dorr et al. 1996. Contains norleucine and a D-amino acid. It differs from bremelanotide only at the C-terminus (amide rather than free acid).", "class_by_jurisdiction": { "US": "C", "EU": "C", "UK": "C", "CA": "C", "AU": "C", "JP": null, "CN": null }, "what_it_is": "A synthetic cyclic peptide related to alpha-melanocyte-stimulating hormone that activates several melanocortin receptors. It was studied in small academic trials in the 1990s for tanning and erectile function, then not developed as a medicine. It is not approved anywhere checked and is sold online as an unlicensed injectable \"tanning\" product. Its documented human record is dominated by case reports of harm: changing and new moles, melanoma, priapism, rhabdomyolysis and kidney injury.", "evidence": [ { "indication": "Skin tanning (the main gray-market claim)", "tier": "E4", "human_rcts": 0, "human_trials_any": 1, "summary": "The only published efficacy data are a pilot phase 1 study in three healthy men (single-blind, alternating days of injection and saline) in which two subjects showed increased facial and body pigmentation. No randomised trial of tanning has been published. No study has tested whether induced tanning reduces sunburn or skin cancer, and case reports describe new and changing moles in users.", "citations": [ { "doi": "10.1016/0024-3205(96)00160-9", "title": "Evaluation of Melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study", "year": 1996, "finding": "Increased skin pigmentation in two of three healthy men; nausea, yawning-stretching and spontaneous erections reported" } ], "trials_query": "melanotan" }, { "indication": "Erectile dysfunction and sexual desire in men", "tier": "E3", "human_rcts": 2, "human_trials_any": 3, "summary": "Small double-blind, placebo-controlled crossover studies from a single US research group in the late 1990s reported erections after injection more often than after placebo, in men with psychogenic and with organic erectile dysfunction, and higher self-rated sexual desire. In the organic study, 12 of 19 injections initiated erections versus 1 of 21 placebo doses, and 4 of 19 injections caused severe nausea. No larger trial has been published.", "citations": [ { "doi": "10.1016/s0090-4295(00)00680-4", "title": "Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction", "year": 2000, "finding": "More erections and higher sexual desire than placebo in a small crossover study; severe nausea after 4 of 19 injections" } ], "trials_query": "melanotan" }, { "indication": "Appetite suppression / weight loss (gray-market claim)", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "Reduced food intake has been shown only in rodents, for example after injection into the brain ventricles of mice. No human study has measured appetite, food intake or body weight as an outcome.", "citations": [ { "doi": "10.1038/385165a0", "title": "Role of melanocortinergic neurons in feeding and the agouti obesity syndrome", "year": 1997, "finding": "Intracerebroventricular MTII inhibited feeding in four mouse models of hyperphagia" } ], "trials_query": "melanotan" } ], "safety": { "grade": "S4", "no_data_statement": true, "known_signals": [ { "signal": "Eruptive and changing melanocytic naevi (moles)", "evidence": "Case reports of new and changing naevi after unlicensed injection; a review highlights melanocytic changes in existing moles and newly emerging (dysplastic) naevi.", "citation": { "doi": "10.1111/j.1365-2133.2009.09362.x", "title": "Eruptive melanocytic naevi following melanotan injection" } }, { "signal": "Melanoma", "evidence": "Case reports of melanoma and melanoma in situ arising during or shortly after use; a review counted four reported melanomas. Causation is not established, and users often also use sunbeds.", "citation": { "doi": "10.1159/000356389", "title": "Melanoma Associated with the Use of Melanotan-II" } }, { "signal": "Melanoma in situ", "evidence": "Australian case report of melanotan-associated melanoma in situ.", "citation": { "doi": "10.1111/j.1440-0960.2012.00915.x", "title": "Melanotan-associated melanoma in situ" } }, { "signal": "Ischaemic priapism", "evidence": "Case report of acute ischaemic priapism requiring surgical decompression after injection; the authors note earlier reports.", "citation": { "doi": "10.1016/j.esxm.2020.100298", "title": "Melanotan Tanning Injection: A Rare Cause of Priapism" } }, { "signal": "Systemic sympathomimetic toxicity and rhabdomyolysis with kidney injury", "evidence": "Case report after injection of an internet-purchased product.", "citation": { "doi": "10.3109/15563650.2012.740637", "title": "Melanotan II injection resulting in systemic toxicity and rhabdomyolysis" } }, { "signal": "Renal infarction", "evidence": "Case report and literature review attributing renal infarction most likely to melanotan II.", "citation": { "doi": "10.1007/s13730-020-00447-z", "title": "Melanotan II: a possible cause of renal infarction: review of the literature and case report" } }, { "signal": "Overall risk profile of unregulated use", "evidence": "Review of unregulated alpha-MSH analogue use summarising cutaneous complications and uncertainties about preparation and contents.", "citation": { "doi": "10.1111/ijd.13585", "title": "Risks of unregulated use of alpha‐melanocyte‐stimulating hormone analogues: a review" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "No FDA-approved application: openFDA Drugs@FDA returns no application with a melanotan active ingredient (query: products.active_ingredients.name:MELANOTAN*). Melanotan II does not appear in any category of FDA's 503A bulk drug substances nomination list (version updated 14 May 2026).", "source_url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:MELANOTAN*", "source_title": "openFDA Drugs@FDA API (FDA)", "quote": "No matches found!", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "unapproved", "detail": "No entry for melanotan II in EMA's downloadable table of centrally authorised medicines (retrieved 2026-10-10). National authorisations were not checked individually; none is known.", "source_url": "https://www.ema.europa.eu/en/medicines/download-medicine-data", "source_title": "EMA: Download medicine data", "quote": "This includes information on marketing authorisations of centrally authorised medicines and post-authorisation procedures.", "retrieved": "2026-10-10" }, { "jurisdiction": "UK", "status": "unapproved", "detail": "A search of the MHRA products database index for 'melanotan' returned no authorised product documents. Historic MHRA public warnings about tanning injections were found only via secondary reports and are not cited here.", "source_url": "https://products.mhra.gov.uk/", "source_title": "MHRA Products", "quote": "Scientific reports about marketing authorisations for medicines", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "unapproved", "detail": "The Health Canada Drug Product Database API returns no product with an active ingredient matching melanotan (https://health-products.canada.ca/api/drug/activeingredient/?lang=en&type=json&ingredientname=melanotan returned an empty list).", "source_url": "https://health-products.canada.ca/api/documentation/dpd-documentation-en.html", "source_title": "Health Canada Drug Product Database (DPD) API Guide", "quote": "The DPD contains product specific information on drugs approved for use in Canada.", "retrieved": "2026-10-10" }, { "jurisdiction": "AU", "status": "unapproved", "detail": "Listed by name in Schedule 4 (Prescription Only Medicine) of the Poisons Standard (October 2026 instrument, F2026L01327, in force). No registered product was found; Schedule 4 listing controls supply and does not indicate approval.", "source_url": "https://www.legislation.gov.au/F2026L01327/asmade/text", "source_title": "Therapeutic Goods (Poisons Standard—October 2026) Instrument 2026 (Federal Register of Legislation)", "quote": "MELANOTAN II cross reference: α–MELANOCYTE STIMULATING HORMONE Schedule 4", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S0", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "trials": [ { "nct": "NCT07437560", "title": "Melanotan II (MT-II) as an Adjunct to NB-UVB Phototherapy for Repigmentation in Stable Nonsegmental Vitiligo", "phase": "2", "status": "Recruiting" } ], "unknowns": [ "No randomised trial of tanning efficacy, and no study of whether induced pigmentation changes sunburn or skin-cancer risk", "Incidence of naevus changes, melanoma, priapism or kidney injury among users is unknown; only case reports exist", "No human pharmacokinetic data for the injectable or nasal products sold online", "No published analytical data on identity, purity, sterility or content of gray-market products", "No long-term human safety data of any kind", "Results of the only registered current trial (NCT07437560, vitiligo, small company sponsor, recruiting) are not available" ], "mechanism": "Melanotan II is a non-selective agonist at several melanocortin receptors; MC1 receptor activation on melanocytes increases melanin production, and central melanocortin receptor activation was associated with erections and reduced feeding in early human and rodent studies.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "mots-c", "names": { "inn": null, "common": [ "MOTS-c", "Mitochondrial open reading frame of the 12S rRNA-c", "Mitochondrial-derived peptide MOTS-c" ], "codes": [], "brands": [], "cas": null }, "sequence": "MRWQEMGYIFYPRKLR", "sequence_note": "16 residues encoded by a short open reading frame within the mitochondrial 12S rRNA gene (UniProt A0A0C5B5G6).", "class_by_jurisdiction": { "US": "C", "EU": null, "UK": null, "CA": null, "AU": null, "JP": null, "CN": null }, "what_it_is": "A 16-amino-acid peptide encoded in mitochondrial DNA and found naturally in human blood and muscle. A synthetic version is sold on the gray market with claims of weight loss, better insulin sensitivity, exercise performance and longevity. It is not approved as a medicine in any jurisdiction checked. FDA states it has identified no human exposure data for products containing it by any route. The World Anti-Doping Agency names it as a prohibited metabolic modulator.", "evidence": [ { "indication": "Obesity, weight loss and insulin resistance", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "The founding study reported that MOTS-c treatment in mice prevented diet-induced obesity and age-related and diet-induced insulin resistance. No published human trial of MOTS-c for weight, glucose control or insulin sensitivity was identified. A placebo-controlled phase 2 trial in adults with prediabetes was registered in China in 2026 and is recruiting, with no results. A company-developed analogue (CB4211) completed a phase 1 trial, but that is a different molecule and its results were not identified in a peer-reviewed journal.", "citations": [ { "doi": "10.1016/j.cmet.2015.02.009", "title": "The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance", "year": 2015, "finding": "MOTS-c treatment prevented diet-induced obesity and insulin resistance in mice" } ], "trials_query": "MOTS-c" }, { "indication": "Exercise performance, physical capacity and ageing", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "In mice, MOTS-c treatment increased running performance in young, middle-aged and old animals, and treatment started late in life increased physical capacity. In humans, the same study measured only endogenous MOTS-c, which rose in muscle and blood with exercise; no human was given MOTS-c. No human trial of administered MOTS-c for exercise capacity, muscle function or ageing outcomes was identified.", "citations": [ { "doi": "10.1038/s41467-020-20790-0", "title": "MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis", "year": 2021, "finding": "MOTS-c treatment increased running capacity in young, middle-aged and old mice; endogenous MOTS-c rose with exercise in humans" } ], "trials_query": "MOTS-c" } ], "safety": { "grade": "S5", "no_data_statement": true, "known_signals": [] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "Not approved: FDA has approved no product containing MOTS-c. FDA's list of bulk substances that may present significant safety risks places MOTs-C among substances previously in 503A Category 2 whose nominations were withdrawn by the nominators; it is not on the current 503A Category 1 or 2 lists (updated 14 May 2026). FDA cites possible immunogenicity and peptide impurity and characterisation concerns.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (FDA, content current as of 04/22/2026)", "quote": "FDA has not identified any human exposure data on drug products containing MOTs-C administered via any route of administration.", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S4.4.1", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Activators of the AMP-activated protein kinase (AMPK), e.g. 5-N,6-N-bis(2-fluorophenyl)-[1,2,5]oxadiazolo[3,4-b]pyrazine-5,6-diamine (BAM15), AICAR, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c)" }, "trials": [ { "nct": "NCT07505745", "title": "MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity", "phase": "2", "status": "Recruiting" } ], "unknowns": [ "No published human data of any kind on administered MOTS-c: no pharmacokinetics, no safety and no efficacy by any route", "Immunogenicity of injected synthetic MOTS-c is unassessed; FDA states compounded MOTS-c may pose significant risk for immunogenicity and raises peptide-impurity and characterisation concerns", "Whether findings in mice on weight, insulin resistance and running capacity apply to humans has not been tested; the first registered human efficacy trial had not reported at review", "Results for the analogue CB4211 were not found in a peer-reviewed journal, and an analogue's effects cannot be assumed for MOTS-c itself", "Regulatory status outside the US was not verified from regulator sources for this record" ], "mechanism": "MOTS-c is a peptide encoded in mitochondrial DNA; in mouse and cell studies it acted mainly on skeletal muscle, inhibiting the folate cycle and de novo purine synthesis and leading to activation of AMP-activated protein kinase (AMPK).", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "octreotide", "names": { "inn": "octreotide", "common": [ "Octreotide", "Octreotide acetate", "SMS 201-995" ], "codes": [ "SMS 201-995" ], "brands": [ "Sandostatin", "Sandostatin LAR", "Mycapssa" ], "cas": null }, "sequence": null, "sequence_note": "Cyclic octapeptide analogue of somatostatin: D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol, disulfide bridge Cys2-Cys7; contains D-amino acids and a C-terminal threoninol, so no standard one-letter sequence is given.", "class_by_jurisdiction": { "US": "A", "EU": null, "UK": null, "CA": "A", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic eight-residue cyclic analogue of the hormone somatostatin, with a longer half-life than the native hormone. It is an approved prescription drug in the United States and Canada in short-acting and long-acting injectable forms, and in the United States as an oral delayed-release capsule. Labelled uses centre on acromegaly and on symptoms of carcinoid and other hormone-secreting neuroendocrine tumours.", "evidence": [ { "indication": "Acromegaly (biochemical control)", "tier": "E2", "human_rcts": 1, "human_trials_any": 2, "summary": "Injectable octreotide has been used in acromegaly since the late 1980s, largely on the basis of uncontrolled and open-label studies. The oral capsule was tested in a randomised, double-blind, placebo-controlled withdrawal trial (OPTIMAL, 56 participants) in people already controlled on injectable somatostatin analogues, and in an open-label randomised non-inferiority trial against injectables (MPOWERED). One adequately designed placebo-controlled RCT is cited here; the outcome is a biochemical marker (IGF-I), not tumour or survival outcomes.", "citations": [ { "doi": "10.1210/clinem/dgaa526", "title": "Maintenance of Acromegaly Control in Patients Switching From Injectable Somatostatin Receptor Ligands to Oral Octreotide", "year": 2020, "finding": "A higher proportion of participants on oral octreotide than on placebo kept IGF-I within the target range in a randomised withdrawal trial in adults with acromegaly" } ], "trials_query": "octreotide" }, { "indication": "Metastatic midgut neuroendocrine tumours (tumour growth control)", "tier": "E2", "human_rcts": 1, "human_trials_any": 1, "summary": "The PROMID trial randomised 85 treatment-naive patients with metastatic well-differentiated midgut neuroendocrine tumours to long-acting octreotide or placebo and reported a longer time to tumour progression with octreotide. No overall survival benefit was established in the primary report. This indication is not part of the US label wording for octreotide.", "citations": [ { "doi": "10.1200/JCO.2009.22.8510", "title": "Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study Group", "year": 2009, "finding": "Longer time to tumour progression with long-acting octreotide than with placebo in patients with metastatic midgut neuroendocrine tumours" } ], "trials_query": "octreotide" }, { "indication": "Carcinoid syndrome (diarrhoea and flushing)", "tier": "E3", "human_rcts": 1, "human_trials_any": 1, "summary": "The cited randomised trial compared long-acting and short-acting octreotide formulations in malignant carcinoid syndrome rather than octreotide against placebo; it was small and partly open-label. Symptom control with the two formulations was reported as similar. Placebo-controlled evidence for symptom relief with octreotide itself was not identified in this review.", "citations": [ { "doi": "10.1200/JCO.1999.17.2.600", "title": "Octreotide Acetate Long-Acting Formulation Versus Open-Label Subcutaneous Octreotide Acetate in Malignant Carcinoid Syndrome", "year": 1999, "finding": "Long-acting and short-acting octreotide formulations gave comparable control of diarrhoea and flushing in patients with malignant carcinoid syndrome" } ], "trials_query": "octreotide carcinoid" }, { "indication": "Acute oesophageal variceal bleeding (off-label)", "tier": "E3", "human_rcts": null, "human_trials_any": null, "summary": "Octreotide is used off-label in acute variceal bleeding. A Cochrane systematic review of randomised trials of somatostatin analogues (somatostatin and octreotide) found no reduction in mortality and only a small effect on the need for transfusion, with trial quality and results varying. The number of octreotide-specific RCTs is not stated here because the review pooled both agents.", "citations": [ { "doi": "10.1002/14651858.CD000193.pub3", "title": "Somatostatin analogues for acute bleeding oesophageal varices", "year": 2008, "finding": "Systematic review of randomised trials found no mortality reduction with somatostatin analogues in acute variceal bleeding" } ], "trials_query": "octreotide variceal" } ], "safety": { "grade": "S1", "no_data_statement": false, "known_signals": [ { "signal": "Gallbladder and biliary stone formation", "evidence": "Gallstones and gallbladder sludge are a labelled warning for somatostatin analogues; a case of intrahepatic stones during octreotide therapy for acromegaly has been reported.", "citation": { "doi": "10.1023/a:1012880113759", "title": "Hepatolithiasis (Intrahepatic Stone) During Octreotide Therapy for Acromegaly: A Case Report" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "approved", "detail": "Sandostatin (NDA 019667, Novartis) is listed in Drugs@FDA with an original approval as a new molecular entity on 21 October 1988. Long-acting (Sandostatin LAR, NDA 021008, 1998) and oral delayed-release (Mycapssa, NDA 208232, 2020) forms are separately listed.", "source_url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019667", "source_title": "Drugs@FDA: FDA-Approved Drugs - NDA 019667 (Sandostatin)", "quote": "10/21/1988 ORIG-1 Approval Type 1 - New Molecular Entity PRIORITY", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "withdrawn", "detail": "This entry covers only the centrally authorised oral capsule (Mycapssa, EMEA/H/C/005826), authorised 2 December 2022 and withdrawn on 26 February 2025 at the holder's request for commercial reasons. Injectable octreotide products in the EU are nationally authorised and were not verified from a regulator page for this record, so the EU class is left unset.", "source_url": "https://www.ema.europa.eu/en/medicines/human/EPAR/mycapssa", "source_title": "Mycapssa | European Medicines Agency (EMA)", "quote": "On 26 February 2025, the European Commission withdrew the marketing authorisation for Mycapssa (octreotide) in the European Union (EU).", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "approved", "detail": "Health Canada Drug Product Database lists Sandostatin (Novartis Pharmaceuticals Canada Inc) with current status Marketed.", "source_url": "https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=9915", "source_title": "Drug Product Database: Product information - SANDOSTATIN", "quote": "Current status: Marketed Current status date: 1998-04-15 Original market date: See footnote 1 1989-12-31 Product name: SANDOSTATIN", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "not_prohibited", "wada_class": null, "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "trials": [ { "nct": "NCT03252353", "title": "Efficacy and Safety of Octreotide Capsules (MYCAPSSA) in Acromegaly", "phase": "3", "status": "Unknown" }, { "nct": "NCT02685709", "title": "Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly", "phase": "3", "status": "Completed" }, { "nct": "NCT00171873", "title": "Antiproliferative Effect of Octreotide in Patients With Metastasized Neuroendocrine Tumors of the Midgut", "phase": "3", "status": "Completed" } ], "unknowns": [ "Whether octreotide improves overall survival in metastatic midgut neuroendocrine tumours has not been shown in the cited placebo-controlled trial", "Placebo-controlled evidence for symptom relief in carcinoid syndrome with octreotide itself was not identified; the cited trial compared two octreotide formulations", "Octreotide-specific effect estimates in acute variceal bleeding are not separable from somatostatin in the cited pooled review", "Status in the UK, Australia, Japan and China was not verified from regulator sources for this record" ], "mechanism": "Octreotide binds somatostatin receptors, mainly subtypes 2 and 5, and in human studies lowers secretion of growth hormone, IGF-I and several gastrointestinal and pancreatic hormones.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "pe-22-28", "names": { "inn": null, "common": [ "PE-22-28", "PE 22-28", "Spadin analogue PE 22-28" ], "codes": [], "brands": [], "cas": null }, "sequence": "GVSWGLR", "sequence_note": "Residues 22-28 of the mouse sortilin propeptide (PE). Derived from the published spadin sequence (PE 12-28, APLPRWSGPIGVSWGLR) and the statement that glycine occupies position 22; the free peptide's terminal groups were not verified.", "class_by_jurisdiction": { "US": "C", "EU": "C", "UK": null, "CA": "C", "AU": null, "JP": null, "CN": null }, "what_it_is": "A seven-amino-acid peptide cut down from spadin, a fragment of the propeptide released when the sorting protein sortilin matures. It was designed in a French laboratory as a blocker of the TREK-1 potassium channel and tested for antidepressant-like activity in mice. It is sold online as a research chemical with claims for depression, mood and cognition. No study in humans was identified and no approved medicine contains it.", "evidence": [ { "indication": "Depression", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "Efficacy data are from mice only. In the 2017 report that introduced it, PE 22-28 reduced immobility in the forced swim test, shortened escape latency in a learned-helplessness test and reduced feeding latency in a novelty-suppressed feeding test, including in a corticosterone-induced depression model, with a longer-lasting effect than its parent peptide spadin. These are behavioural screening tests in mice; no human study of mood, depression or any other outcome was identified.", "citations": [ { "doi": "10.3389/fphar.2017.00643", "title": "Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity", "year": 2017, "finding": "Inhibited TREK-1 channels in a human cell line and reduced depression-like behaviour in mouse forced-swim, learned-helplessness and novelty-suppressed feeding tests" }, { "doi": "10.1371/journal.pbio.1000355", "title": "Spadin, a Sortilin-Derived Peptide, Targeting Rodent TREK-1 Channels: A New Concept in the Antidepressant Drug Design", "year": 2010, "finding": "The parent peptide spadin blocked TREK-1 and reduced depression-like behaviour in mice (spadin, not PE 22-28)" } ], "trials_query": "PE-22-28" } ], "safety": { "grade": "S5", "no_data_statement": true, "known_signals": [] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "No FDA-approved application: openFDA Drugs@FDA returns no application with a PE-22-28 active ingredient (query: products.active_ingredients.name:\"PE-22-28\"). PE-22-28 does not appear in Category 1, 2 or 3 of FDA's 503A bulk drug substances nomination list (updated 14 May 2026). openFDA states its data are unvalidated.", "source_url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22PE-22-28%22", "source_title": "openFDA Drugs@FDA API (FDA)", "quote": "No matches found!", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "unapproved", "detail": "No product containing PE-22-28 or spadin appears in EMA's downloadable medicines dataset (generated 10 Oct 2026), which covers centrally authorised medicines, refusals and withdrawn applications. National authorisations were not checked individually.", "source_url": "https://www.ema.europa.eu/en/medicines/download-medicine-data", "source_title": "Download medicine data | European Medicines Agency (EMA)", "quote": "This includes information on marketing authorisations of centrally authorised medicines and post-authorisation procedures.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "unapproved", "detail": "A query of Health Canada's Drug Product Database API for the active ingredient spadin returned no products on the retrieval date; PE-22-28 has no ingredient name under which it could be listed.", "source_url": "https://health-products.canada.ca/dpd-bdpp/?lang=eng", "source_title": "Drug Product Database online query", "quote": "Search by drug identification number", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S0", "detail": "PE-22-28 is not named on the 2026 Prohibited List; as a substance with no governmental approval for human use identified, it falls under class S0.", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "unknowns": [ "No human data of any kind were identified: no pharmacokinetic, safety or efficacy study in people", "Whether TREK-1 blockade in humans affects heart rhythm, pain sensitivity or seizure threshold is unstudied for this peptide; TREK-1 is expressed in heart and nerve tissue", "Mouse behavioural tests such as the forced swim test screen for antidepressant-like activity and do not establish an effect on human depression", "Identity, purity and terminal modifications of material sold as PE-22-28 are uncharacterised", "Status in the UK, Australia, Japan and China was not verified from regulator sources for this record" ], "mechanism": "PE-22-28 blocks the TREK-1 two-pore-domain potassium channel; in cultured cells expressing human TREK-1 it inhibited channel currents with higher potency than spadin.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "retatrutide", "names": { "inn": "retatrutide", "common": [ "Retatrutide" ], "codes": [ "LY3437943" ], "brands": [], "cas": null }, "sequence": null, "sequence_note": "Synthetic lipidated peptide containing non-coded amino acids; full structure not verified for this record.", "class_by_jurisdiction": { "US": "B", "EU": "B", "UK": "B", "CA": "B", "AU": "B", "JP": "B", "CN": "B" }, "what_it_is": "An investigational synthetic peptide from Eli Lilly that activates three hormone receptors: GIP, GLP-1 and glucagon. It is in phase 3 development for obesity, type 2 diabetes and related conditions. It is not approved in any jurisdiction checked. The UK MHRA states it is not authorised and that products sold under the name are sold illegally; case reports describe harm after use of online-purchased material.", "evidence": [ { "indication": "Weight reduction in obesity or overweight (the main use it is sold for)", "tier": "E1", "human_rcts": null, "human_trials_any": null, "summary": "Two published phase 3 trials and one phase 2 trial. TRIUMPH-1 (2,339 adults without diabetes, 80 weeks): mean weight change -17.6% to -25.0% across dose groups versus -3.9% with placebo. TRIUMPH-2 (1,152 adults with obesity and type 2 diabetes, 80 weeks): -11.9% to -18.8% versus -5.1%. The phase 2 trial (338 adults, 48 weeks) reported -8.7% to -24.2% versus -2.1%. Phase 3 results of TRIUMPH-3 and TRIUMPH-4 (both completed on ClinicalTrials.gov) were not located in a publication.", "citations": [ { "doi": "10.1056/nejmoa2604169", "title": "Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity", "year": 2026, "finding": "TRIUMPH-1: weight change -17.6% to -25.0% vs -3.9% with placebo at 80 weeks in adults with obesity without diabetes" }, { "doi": "10.1016/s0140-6736(26)01861-1", "title": "Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial", "year": 2026, "finding": "TRIUMPH-2: weight change -11.9% to -18.8% vs -5.1% with placebo at 80 weeks in obesity with type 2 diabetes" }, { "doi": "10.1056/NEJMoa2301972", "title": "Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial", "year": 2023, "finding": "Phase 2: weight change up to -24.2% vs -2.1% with placebo at 48 weeks" } ], "trials_query": "retatrutide AND obesity" }, { "indication": "Type 2 diabetes: glycaemic control", "tier": "E2", "human_rcts": null, "human_trials_any": null, "summary": "One published phase 3 trial (TRANSCEND-T2D-1, 537 adults managed with diet and exercise alone, 40 weeks): HbA1c fell 1.69 to 1.94 percentage points versus 0.81 with placebo. A phase 2 trial (281 participants) also reported HbA1c reductions. Phase 3 trials versus semaglutide (TRANSCEND-T2D-2) and in renal impairment (TRANSCEND-T2D-3) have not reported.", "citations": [ { "doi": "10.1016/s0140-6736(26)00967-0", "title": "Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial", "year": 2026, "finding": "HbA1c change -1.69% to -1.94% vs -0.81% with placebo at 40 weeks" }, { "doi": "10.1016/S0140-6736(23)01053-X", "title": "Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA", "year": 2023, "finding": "Phase 2: dose-dependent HbA1c reductions at 24 weeks in type 2 diabetes" } ], "trials_query": "retatrutide AND type 2 diabetes" }, { "indication": "Knee osteoarthritis pain with obesity", "tier": "E2", "human_rcts": null, "human_trials_any": null, "summary": "In a 574-participant knee osteoarthritis subgroup of TRIUMPH-1, WOMAC pain scores improved more with retatrutide than placebo (differences -1.6 and -1.8 points on a 10-point scale, hybrid estimand). The dedicated knee osteoarthritis trial (TRIUMPH-4, NCT05931367) is completed on ClinicalTrials.gov but no publication was located.", "citations": [ { "doi": "10.1056/nejmoa2604169", "title": "Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity", "year": 2026, "finding": "WOMAC pain differences -1.6 and -1.8 points vs placebo in the knee osteoarthritis subgroup" } ], "trials_query": "retatrutide AND osteoarthritis" }, { "indication": "Obstructive sleep apnoea with obesity", "tier": "E2", "human_rcts": null, "human_trials_any": null, "summary": "In a 243-participant obstructive sleep apnoea subgroup of TRIUMPH-1, the apnoea-hypopnoea index fell by about 22 to 24 more events per hour than with placebo (both comparisons P<0.001). No standalone sleep apnoea trial result has been published.", "citations": [ { "doi": "10.1056/nejmoa2604169", "title": "Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity", "year": 2026, "finding": "AHI differences -24.4 and -21.9 events per hour vs placebo in the sleep apnoea subgroup" } ], "trials_query": "retatrutide AND sleep apnea" }, { "indication": "Liver fat (metabolic dysfunction-associated steatotic liver disease)", "tier": "E3", "human_rcts": null, "human_trials_any": null, "summary": "Evidence is a substudy of the phase 2 obesity trial (98 participants with at least 10% liver fat). Relative liver-fat change at 24 weeks ranged from -42.9% to -82.4% across dose groups versus +0.3% with placebo. Liver fat is a surrogate endpoint; no histology or liver-outcome trial has reported.", "citations": [ { "doi": "10.1038/s41591-024-03018-2", "title": "Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial", "year": 2024, "finding": "Relative liver-fat change -42.9% to -82.4% vs +0.3% with placebo at 24 weeks (n=98)" } ], "trials_query": "retatrutide AND liver" } ], "safety": { "grade": "S2", "no_data_statement": true, "known_signals": [ { "signal": "Gastrointestinal adverse events", "evidence": "In TRIUMPH-2, diarrhoea occurred in 27-34% and nausea in 14-28% of retatrutide groups versus 13% and 8% with placebo. Treatment discontinuation for adverse events or death reached 12% in one dose group versus 5% with placebo.", "citation": { "doi": "10.1016/s0140-6736(26)01861-1", "title": "Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial" } }, { "signal": "Dysaesthesia (abnormal skin sensation) and hypotension", "evidence": "In TRIUMPH-2, dysaesthesia occurred in 4-7% versus 1% and hypotension in 1-6% versus <1% with placebo, increasing with dose.", "citation": { "doi": "10.1016/s0140-6736(26)01861-1", "title": "Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial" } }, { "signal": "Heart rate increase", "evidence": "In the phase 2 obesity trial, dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter.", "citation": { "doi": "10.1056/NEJMoa2301972", "title": "Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial" } }, { "signal": "Harm after use of unlicensed online product", "evidence": "Case report: a man with type 1 diabetes developed vomiting, diarrhoea, ketonaemia and acute kidney injury after self-administering an online-purchased product marketed as retatrutide (concurrent Shigella infection). Product identity was not confirmed.", "citation": { "doi": "10.7759/cureus.115260", "title": "Online-Sourced Retatrutide Complicating Impending Diabetic Ketoacidosis in a Patient With Type 1 Diabetes and Concurrent Shigella Gastroenteritis" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "investigational", "detail": "No Drugs@FDA application found for retatrutide (openFDA Drugs@FDA query by active ingredient returns no records). Phase 3 trials sponsored by Eli Lilly are registered on ClinicalTrials.gov.", "source_url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:retatrutide", "source_title": "openFDA Drugs@FDA API query: active ingredient retatrutide", "quote": "\"code\": \"NOT_FOUND\", \"message\": \"No matches found!\"", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "investigational", "detail": "Retatrutide does not appear in the EMA medicines dataset (2,748 records of centrally processed medicines, timestamp 2026-10-10).", "source_url": "https://www.ema.europa.eu/en/documents/report/medicines-output-medicines_json-report_en.json", "source_title": "EMA medicines data (JSON report)", "quote": "\"total_records\": 2748, \"timestamp\": \"2026-10-10T06:02:36Z\"", "retrieved": "2026-10-10" }, { "jurisdiction": "UK", "status": "investigational", "detail": "MHRA press release (24 July 2026) states retatrutide is not authorised in the UK.", "source_url": "https://www.gov.uk/government/news/no-summer-shortcut-for-safe-weight-loss", "source_title": "No summer shortcut for safe weight loss (MHRA)", "quote": "It has not been authorised for use in the UK, meaning anyone selling this product is doing so illegally.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "investigational", "detail": "Health Canada Drug Product Database active-ingredient query for retatrutide returns an empty result.", "source_url": "https://health-products.canada.ca/api/drug/activeingredient/?lang=en&type=json&ingredientname=retatrutide", "source_title": "Health Canada Drug Product Database API: active ingredient retatrutide", "quote": "[]", "retrieved": "2026-10-10" }, { "jurisdiction": "AU", "status": "investigational", "detail": "TGA Product Information repository search for retatrutide returns no documents.", "source_url": "https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=PI&q=retatrutide", "source_title": "TGA eBS - Product and Consumer Medicine Information (search: retatrutide)", "quote": "Search PI Trade Names and Active Ingredients containing retatrutide . 0 Documents available.", "retrieved": "2026-10-10" }, { "jurisdiction": "JP", "status": "investigational", "detail": "Retatrutide does not appear in the PMDA List of Approved Products (New Drugs), which covers approvals through February 2026; later approvals would not be shown.", "source_url": "https://www.pmda.go.jp/files/000281190.pdf", "source_title": "PMDA List of Approved Products: New Drugs (April 2004 to February 2026)", "quote": "April 2004 to February 2026", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S0", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development" }, "trials": [ { "nct": "NCT05929066", "title": "A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight", "phase": "3", "status": "Completed" }, { "nct": "NCT05929079", "title": "A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight", "phase": "3", "status": "Completed" }, { "nct": "NCT05882045", "title": "A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease", "phase": "3", "status": "Completed" }, { "nct": "NCT05931367", "title": "A Study of Retatrutide (LY3437943) Once Weekly in Participants Who Have Obesity or Overweight and Osteoarthritis of the Knee", "phase": "3", "status": "Completed" }, { "nct": "NCT06662383", "title": "A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have Obesity", "phase": "3", "status": "Active, not recruiting" }, { "nct": "NCT06859268", "title": "A Study of Retatrutide (LY3437943) in the Maintenance of Weight Reduction in Individuals With Obesity", "phase": "3", "status": "Active, not recruiting" }, { "nct": "NCT06383390", "title": "The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults Living With Obesity (TRIUMPH-Outcomes)", "phase": "3", "status": "Active, not recruiting" }, { "nct": "NCT06354660", "title": "Effect of Retatrutide Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone (TRANSCEND-T2D-1)", "phase": "3", "status": "Completed" }, { "nct": "NCT06260722", "title": "Effect of Retatrutide Compared With Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin With or Without SGLT2 Inhibitor (TRANSCEND-T2D-2)", "phase": "3", "status": "Active, not recruiting" }, { "nct": "NCT06297603", "title": "Effect of Retatrutide Compared With Placebo in Participants With Type 2 Diabetes and Moderate or Severe Renal Impairment, With Inadequate Glycemic Control on Basal Insulin, With or Without Metformin and/or SGLT2 Inhibitor (TRANSCEND-T2D-3)", "phase": "3", "status": "Active, not recruiting" }, { "nct": "NCT04881760", "title": "A Study of LY3437943 in Participants Who Have Obesity or Are Overweight", "phase": "2", "status": "Completed" }, { "nct": "NCT04867785", "title": "A Study of LY3437943 in Participants With Type 2 Diabetes", "phase": "2", "status": "Completed" } ], "unknowns": [ "Effect on cardiovascular and kidney outcomes; TRIUMPH-Outcomes (NCT06383390) is ongoing", "Safety beyond 80 weeks of exposure, the longest duration in published randomised trials", "Mechanism, course and reversibility of the dysaesthesia signal seen in phase 3", "Results of completed phase 3 trials TRIUMPH-3 and TRIUMPH-4, which were not located in a peer-reviewed publication as of 2026-10-10", "Identity, purity, sterility and content of material sold online under the retatrutide name; no lawful supply exists and no systematic assay data were located" ], "mechanism": "Retatrutide is a single peptide with agonist activity at the GIP, GLP-1 and glucagon receptors.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "selank", "names": { "inn": null, "common": [ "Selank", "Selank acetate", "TP-7", "Thr-Lys-Pro-Arg-Pro-Gly-Pro" ], "codes": [ "TP-7" ], "brands": [], "cas": null }, "sequence": "TKPRPGP", "sequence_note": "Heptapeptide: the immune peptide tuftsin (Thr-Lys-Pro-Arg) extended with Pro-Gly-Pro at the C-terminus for stability.", "class_by_jurisdiction": { "US": "C", "EU": "C", "UK": null, "CA": "C", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic seven-amino-acid peptide made by adding a Pro-Gly-Pro tail to tuftsin, a short peptide derived from an antibody fragment. It was developed in Russia as an anti-anxiety agent, and its clinical literature is almost entirely Russian. It is sold online elsewhere as a research chemical with claims for anxiety, focus and memory. No approved medicine contains it in any jurisdiction checked for this record.", "evidence": [ { "indication": "Anxiety disorders", "tier": "E3", "human_rcts": null, "human_trials_any": 3, "summary": "Three small Russian clinical studies were identified, none placebo-controlled. In 62 patients with generalised anxiety disorder or neurasthenia, selank and the benzodiazepine medazepam had similar anxiolytic effects. In 60 patients with anxiety and somatoform disorders, selank was compared with phenazepam. In 70 patients, adding selank to phenazepam was reported to bring an earlier response and fewer benzodiazepine side effects. PubMed indexes two of these as randomised; the designs were not verified from full texts, so the RCT count is left blank. Without placebo arms these studies cannot separate drug effect from the high placebo response typical of anxiety trials.", "citations": [ { "pmid": 18454096, "title": "[Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia].", "year": 2008, "finding": "Similar anxiolytic effect of selank and medazepam in 62 patients with generalised anxiety disorder or neurasthenia" }, { "pmid": 25176261, "title": "[A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders].", "year": 2014, "finding": "Anxiolytic effect reported with selank in a comparison with phenazepam in 60 patients with anxiety and somatoform disorders" }, { "doi": "10.17116/jnevro20151156133-40", "title": "Optimization of the treatment of anxiety disorders with selank", "year": 2015, "finding": "Earlier response and fewer phenazepam side effects reported when selank was added to phenazepam in 70 patients with anxiety disorders" } ], "trials_query": "selank" }, { "indication": "Cognitive enhancement (memory, attention)", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "Memory findings are from rodents: in rats given ethanol long term, selank prevented memory and attention impairment in an object-recognition test and prevented an ethanol-induced rise in hippocampal BDNF. No human trial with cognitive performance as an outcome in healthy people was identified; one anxiety trial above used attention tests as secondary measures in patients also taking phenazepam.", "citations": [ { "doi": "10.1007/s10517-019-04588-9", "title": "Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats", "year": 2019, "finding": "Prevented ethanol-induced memory and attention impairment in an object-recognition test in rats" } ], "trials_query": "selank" }, { "indication": "Stroke", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "One small rat study of experimental intracerebral haemorrhage (five animals per group) reported better functional recovery with selank without an effect on haematoma volume or swelling. No human study of selank in stroke was identified.", "citations": [ { "pmid": 20873405, "title": "[Experimental hemorrhagic stroke: the study of neuropeptides (MIF, selank) in the intraperitoneal injection].", "year": 2009, "finding": "Improved functional recovery without change in haematoma volume in a rat model of intracerebral haemorrhage" } ], "trials_query": "selank" } ], "safety": { "grade": "S4", "no_data_statement": true, "known_signals": [] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "No FDA-approved application: openFDA Drugs@FDA returns no application with a selank active ingredient (query: products.active_ingredients.name:SELANK*). openFDA states its data are unvalidated.", "source_url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:SELANK*", "source_title": "openFDA Drugs@FDA API (FDA)", "quote": "No matches found!", "retrieved": "2026-10-10" }, { "jurisdiction": "US", "status": "unapproved", "detail": "Selank acetate (TP-7) appears on FDA's list of bulk drug substances previously in Category 2 (significant safety risks) of the compounding interim policy whose nominations were withdrawn by the nominators. FDA's safety statement remains on the page.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026)", "quote": "Compounded drugs containing selank acetate may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation and peptide-related impurities. FDA lacks important information regarding any safety issues raised by selank acetate administered to humans.", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "unapproved", "detail": "No product containing selank appears in EMA's downloadable medicines dataset (generated 10 Oct 2026), which covers centrally authorised medicines, refusals and withdrawn applications. National authorisations were not checked individually.", "source_url": "https://www.ema.europa.eu/en/medicines/download-medicine-data", "source_title": "Download medicine data | European Medicines Agency (EMA)", "quote": "This includes information on marketing authorisations of centrally authorised medicines and post-authorisation procedures.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "unapproved", "detail": "Queries of Health Canada's Drug Product Database API for the active ingredient and brand name selank returned no products on the retrieval date.", "source_url": "https://health-products.canada.ca/dpd-bdpp/?lang=eng", "source_title": "Drug Product Database online query", "quote": "Search by drug identification number", "retrieved": "2026-10-10" } ], "unknowns": [ "Sport status is not given: selank is not named on the 2026 WADA Prohibited List, and whether class S0 applies depends on whether any governmental health authority has approved it, which this record did not verify from a regulator source outside the tracked jurisdictions", "No placebo-controlled trial of selank in any anxiety disorder was identified", "No human trial of cognitive performance in healthy people was identified", "No systematic human safety data were identified; FDA states it lacks important information on safety issues raised by selank acetate administered to humans", "Long-term effects of repeated use, including dependence or withdrawal, are not described in the sources reviewed", "Status in the UK, Australia, Japan and China was not verified from regulator sources for this record" ], "mechanism": "Selank is a stabilised analogue of tuftsin; in rodent and cell studies it altered expression of genes involved in GABA signalling and inflammation and changed brain BDNF levels.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "semaglutide", "names": { "inn": "semaglutide", "common": [ "Semaglutide" ], "codes": [ "NN9535" ], "brands": [ "Ozempic", "Wegovy", "Rybelsus", "Kayshild" ], "cas": "910463-68-2" }, "sequence": null, "sequence_note": "Acylated analogue of human GLP-1 containing a non-coded amino acid (Aib) and a fatty diacid side chain attached via a linker; not representable as a plain one-letter sequence.", "class_by_jurisdiction": { "US": "A", "EU": "A", "UK": "A", "CA": "A", "AU": "A", "JP": "A", "CN": null }, "what_it_is": "A modified version of the gut hormone GLP-1, engineered to persist far longer in the body than the native hormone. It is an approved prescription medicine for type 2 diabetes (Ozempic, and Rybelsus as a tablet) and for chronic weight management (Wegovy), with later approvals in some jurisdictions for cardiovascular risk reduction (UK) and MASH (EU, as Kayshild). Falsified and unlicensed products have been reported by the UK MHRA. Status in China was not verified for this record.", "evidence": [ { "indication": "Type 2 diabetes: glycaemic control and cardiovascular outcomes", "tier": "E1", "human_rcts": null, "human_trials_any": null, "summary": "Supported by a large phase 3 programme. In SUSTAIN-6 (3,297 people with type 2 diabetes at high cardiovascular risk), major adverse cardiovascular events occurred in 6.6% on semaglutide versus 8.9% on placebo (hazard ratio 0.74). In FLOW (3,533 people with type 2 diabetes and chronic kidney disease), the composite kidney and cardiovascular outcome was 24% lower with semaglutide (hazard ratio 0.76); the trial stopped early for efficacy.", "citations": [ { "doi": "10.1056/NEJMoa1607141", "title": "Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes", "year": 2016, "finding": "Primary cardiovascular outcome in 6.6% vs 8.9% with placebo (HR 0.74) in people with type 2 diabetes" }, { "doi": "10.1056/NEJMoa2403347", "title": "Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes", "year": 2024, "finding": "Composite kidney/cardiovascular outcome reduced (HR 0.76) in type 2 diabetes with chronic kidney disease" } ], "trials_query": "semaglutide AND type 2 diabetes" }, { "indication": "Chronic weight management (obesity or overweight)", "tier": "E1", "human_rcts": null, "human_trials_any": null, "summary": "Multiple large placebo-controlled trials (the STEP programme). In STEP 1 (1,961 adults without diabetes), mean body-weight change at week 68 was -14.9% with semaglutide versus -2.4% with placebo. In SELECT (17,604 adults with overweight or obesity and established cardiovascular disease, no diabetes), major cardiovascular events occurred in 6.5% versus 8.0% (hazard ratio 0.80). Discontinuation for adverse events was about twice as common with semaglutide (16.6% vs 8.2%).", "citations": [ { "doi": "10.1056/NEJMoa2032183", "title": "Once-Weekly Semaglutide in Adults with Overweight or Obesity", "year": 2021, "finding": "Mean weight change -14.9% vs -2.4% with placebo at week 68 in adults with overweight or obesity" }, { "doi": "10.1056/NEJMoa2307563", "title": "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes", "year": 2023, "finding": "Major adverse cardiovascular events 6.5% vs 8.0% (HR 0.80) in adults with cardiovascular disease and overweight/obesity" } ], "trials_query": "semaglutide AND obesity" }, { "indication": "Heart failure with preserved ejection fraction and obesity", "tier": "E2", "human_rcts": null, "human_trials_any": null, "summary": "In STEP-HFpEF (529 adults with HFpEF and obesity), the heart-failure symptom score (KCCQ-CSS) improved by 16.6 points with semaglutide versus 8.7 with placebo, and body weight fell 13.3% versus 2.6%. The trial measured symptoms and function; it was not powered for heart-failure hospitalisation or death.", "citations": [ { "doi": "10.1056/NEJMoa2306963", "title": "Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity", "year": 2023, "finding": "KCCQ-CSS change 16.6 vs 8.7 points with placebo in HFpEF with obesity" } ], "trials_query": "semaglutide AND heart failure" }, { "indication": "Metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis", "tier": "E2", "human_rcts": null, "human_trials_any": null, "summary": "In the first part of the phase 3 ESSENCE trial (800 patients with biopsy data), resolution of steatohepatitis without worsening fibrosis occurred in 62.9% with semaglutide versus 34.3% with placebo, and fibrosis improvement in 36.8% versus 22.4%. These are histological surrogate endpoints; the clinical-outcomes part of ESSENCE is still under way (ClinicalTrials.gov status: active, not recruiting).", "citations": [ { "doi": "10.1056/NEJMoa2413258", "title": "Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis", "year": 2025, "finding": "MASH resolution 62.9% vs 34.3%; fibrosis improvement 36.8% vs 22.4% with placebo" } ], "trials_query": "semaglutide AND steatohepatitis" }, { "indication": "Knee osteoarthritis pain with obesity", "tier": "E2", "human_rcts": null, "human_trials_any": null, "summary": "One phase 3 trial (STEP 9, 407 participants with obesity and knee osteoarthritis): WOMAC pain score fell 41.7 points with semaglutide versus 27.5 with placebo at week 68, alongside 13.7% versus 3.2% weight loss. The trial cannot separate a direct joint effect from the effect of weight loss.", "citations": [ { "doi": "10.1056/NEJMoa2403664", "title": "Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis", "year": 2024, "finding": "WOMAC pain change -41.7 vs -27.5 points with placebo at week 68" } ], "trials_query": "semaglutide AND osteoarthritis" }, { "indication": "Alcohol use disorder (off-label, claimed)", "tier": "E3", "human_rcts": null, "human_trials_any": null, "summary": "One small randomised trial (48 participants, 9 weeks) found less alcohol consumed in a laboratory self-administration task and fewer drinks per drinking day, but no change in drinks per calendar day or number of drinking days. No adequately powered trial has reported.", "citations": [ { "doi": "10.1001/jamapsychiatry.2024.4789", "title": "Once-Weekly Semaglutide in Adults With Alcohol Use Disorder", "year": 2025, "finding": "Reduced laboratory alcohol self-administration and drinks per drinking day; no change in drinking days (n=48)" } ], "trials_query": "semaglutide AND alcohol" }, { "indication": "Early Alzheimer's disease (oral semaglutide)", "tier": "E1", "human_rcts": null, "human_trials_any": null, "summary": "Two adequately powered phase 3 trials (evoke and evoke+, 3,808 participants in total) found no slowing of clinical progression: change in CDR-SB at week 104 did not differ from placebo in either trial. The tier reflects the strength of the evidence, which consistently shows no benefit.", "citations": [ { "doi": "10.1016/s0140-6736(26)00514-3", "title": "Semaglutide for Alzheimer's disease after evoke and evoke+", "year": 2026, "finding": "Commentary on evoke/evoke+, in which semaglutide did not slow CDR-SB progression versus placebo in early Alzheimer's disease" } ], "trials_query": "semaglutide AND Alzheimer" } ], "safety": { "grade": "S1", "no_data_statement": false, "known_signals": [ { "signal": "Gastrointestinal adverse events, including pancreatitis, bowel obstruction and gastroparesis", "evidence": "Nausea, vomiting and diarrhoea are the most common adverse events in all trials. A US claims-database cohort found higher risk of pancreatitis, bowel obstruction and gastroparesis (not biliary disease) with GLP-1 receptor agonists used for weight loss than with bupropion-naltrexone; confidence intervals were wide. The UK MHRA strengthened pancreatitis warnings for the class in January 2026.", "citation": { "doi": "10.1001/jama.2023.19574", "title": "Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss" } }, { "signal": "Gallbladder and biliary disease", "evidence": "Meta-analysis of 76 randomised trials (103,371 patients): GLP-1 receptor agonist use associated with increased risk of gallbladder or biliary disease (RR 1.37), higher in weight-loss trials (RR 2.29) and at higher doses.", "citation": { "doi": "10.1001/jamainternmed.2022.0338", "title": "Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases" } }, { "signal": "Non-arteritic anterior ischaemic optic neuropathy (NAION)", "evidence": "Retrospective matched cohort of neuro-ophthalmology patients at one academic institution reported higher NAION risk with semaglutide (HR 4.28 in type 2 diabetes). The MHRA issued a Drug Safety Update on NAION risk for Wegovy, Ozempic and Rybelsus (February 2026).", "citation": { "doi": "10.1001/jamaophthalmol.2024.2296", "title": "Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide" } }, { "signal": "Diabetic retinopathy complications in type 2 diabetes", "evidence": "In SUSTAIN-6, retinopathy complications (vitreous haemorrhage, blindness, or conditions requiring treatment) were more frequent with semaglutide than placebo.", "citation": { "doi": "10.1056/NEJMoa1607141", "title": "Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes" } }, { "signal": "Thyroid C-cell tumours in rodents", "evidence": "GLP-1 receptor agonists activate thyroid C-cells and cause C-cell proliferation in rodents; relevance to humans is not established.", "citation": { "doi": "10.1210/en.2009-1272", "title": "Glucagon-Like Peptide-1 Receptor Agonists Activate Rodent Thyroid C-Cells Causing Calcitonin Release and C-Cell Proliferation" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "approved", "detail": "Drugs@FDA NDA 209637 (Ozempic, Novo Nordisk), original approval 12/05/2017 as a new molecular entity. Wegovy is NDA 215256 (approved 06/04/2021); Rybelsus is NDA 213051 (approved 09/20/2019).", "source_url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209637", "source_title": "Drugs@FDA: FDA-Approved Drugs, NDA 209637", "quote": "12/05/2017 ORIG-1 Approval Type 1 - New Molecular Entity STANDARD", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "approved", "detail": "Centrally authorised as Ozempic (8 February 2018); also Rybelsus (2020), Wegovy (2022) and Kayshild (MASH, 2026), per the EMA medicines dataset.", "source_url": "https://www.ema.europa.eu/en/medicines/human/EPAR/ozempic", "source_title": "Ozempic | European Medicines Agency (EPAR)", "quote": "The European Commission granted a marketing authorisation valid throughout the European Union for Ozempic on 8 February 2018.", "retrieved": "2026-10-10" }, { "jurisdiction": "UK", "status": "approved", "detail": "MHRA press release of 23 July 2024 approving a cardiovascular risk-reduction indication for Wegovy, which it states was already approved for obesity and weight management.", "source_url": "https://www.gov.uk/government/news/mhra-approves-glp-1-receptor-agonist-semaglutide-to-reduce-risk-of-serious-heart-problems-in-obese-or-overweight-adults", "source_title": "MHRA approves GLP-1 receptor agonist semaglutide to reduce risk of serious heart problems in obese or overweight adults", "quote": "The Medicines and Healthcare products Regulatory Agency (MHRA) has today, 23 July 2024, approved a new indication for semaglutide (Wegovy) to reduce the risk of overweight and obese adults suffering serious heart problems or strokes.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "approved", "detail": "Health Canada Drug Product Database, Ozempic (drug code 96058), status Marketed since 2018-02-22. Wegovy and Rybelsus are also listed, as are subsequent-entry semaglutide products approved in 2026.", "source_url": "https://health-products.canada.ca/api/drug/status/?lang=en&type=json&id=96058", "source_title": "Health Canada Drug Product Database API: status, drug code 96058 (Ozempic)", "quote": "\"drug_code\":96058,\"status\":\"Marketed\",\"history_date\":\"2018-02-22\",\"original_market_date\":\"2018-02-22\"", "retrieved": "2026-10-10" }, { "jurisdiction": "AU", "status": "approved", "detail": "TGA Product Information repository lists PIs for Ozempic and Wegovy (semaglutide). The main TGA ARTG search (tga.gov.au) timed out on retrieval; the PI repository is a TGA database of registered products.", "source_url": "https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=PI&q=semaglutide", "source_title": "TGA eBS - Product and Consumer Medicine Information (search: semaglutide)", "quote": "Search PI Trade Names and Active Ingredients containing semaglutide . 2 Documents available.", "retrieved": "2026-10-10" }, { "jurisdiction": "JP", "status": "approved", "detail": "PMDA List of Approved Products (New Drugs, April 2004 to February 2026): Ozempic approved Mar. 23, 2018 as a new active ingredient for type 2 diabetes; Rybelsus approved Jun. 29, 2020; Wegovy approved Mar. 27, 2023 for obesity.", "source_url": "https://www.pmda.go.jp/files/000281190.pdf", "source_title": "PMDA List of Approved Products: New Drugs (April 2004 to February 2026)", "quote": "A drug with a new active ingredient indicated for the treatment of type 2 diabetes mellitus.", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "not_prohibited", "wada_class": null, "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development" }, "trials": [ { "nct": "NCT01720446", "title": "Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes", "phase": "3", "status": "Completed" }, { "nct": "NCT03548935", "title": "STEP 1: Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity", "phase": "3", "status": "Completed" }, { "nct": "NCT03574597", "title": "Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity", "phase": "3", "status": "Completed" }, { "nct": "NCT03819153", "title": "A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease", "phase": "3", "status": "Completed" }, { "nct": "NCT04788511", "title": "Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity", "phase": "3", "status": "Completed" }, { "nct": "NCT04822181", "title": "Research Study on Whether Semaglutide Works in People With Non-alcoholic Steatohepatitis (NASH)", "phase": "3", "status": "Active, not recruiting" }, { "nct": "NCT04777396", "title": "A Research Study Investigating Semaglutide in People With Early Alzheimer's Disease (EVOKE)", "phase": "3", "status": "Completed" }, { "nct": "NCT04777409", "title": "A Research Study Investigating Semaglutide in People With Early Alzheimer's Disease (EVOKE Plus)", "phase": "3", "status": "Completed" } ], "unknowns": [ "Long-term effects beyond roughly four years of continuous exposure; the longest outcome trial (SELECT) had mean follow-up of about 40 months", "Whether the NAION association reported in observational data is causal, and its absolute risk in the general treated population", "Human relevance of the thyroid C-cell tumours seen in rodents; no adequately sized long-term human study has resolved it", "Effects of discontinuation on weight and cardiometabolic outcomes over years after stopping", "Identity, purity and content of compounded and unlicensed semaglutide products, which have not been systematically assayed in the published literature" ], "mechanism": "Semaglutide is a GLP-1 receptor agonist. Its fatty-acid side chain binds albumin, which slows clearance and prolongs its duration of action.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "semax", "names": { "inn": null, "common": [ "Semax", "ACTH(4-7)PGP", "ACTH(4-10) analogue Semax", "Met-Glu-His-Phe-Pro-Gly-Pro" ], "codes": [], "brands": [], "cas": null }, "sequence": "MEHFPGP", "sequence_note": "Heptapeptide: the ACTH(4-7) fragment Met-Glu-His-Phe extended with Pro-Gly-Pro at the C-terminus. It has no corticotropic (adrenal-stimulating) activity attributed to it in the literature cited.", "class_by_jurisdiction": { "US": "C", "EU": "C", "UK": null, "CA": "C", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic seven-amino-acid peptide built from a fragment of the hormone ACTH with a Pro-Gly-Pro tail added for stability. It was developed in Russia, where most of its clinical literature was published. It is sold online elsewhere as a research chemical with claims of improving cognition and focus and of protecting the brain after stroke. No approved medicine contains it in any jurisdiction checked for this record.", "evidence": [ { "indication": "Recovery after ischaemic stroke", "tier": "E4", "human_rcts": null, "human_trials_any": null, "summary": "Two Russian clinical reports in people with ischaemic stroke compared semax added to standard care with standard care alone: a 1997 study of 30 treated patients against 80 controls, and a 2018 study of 110 patients divided by rehabilitation timing and semax use. Both reported faster recovery of neurological or motor function and, in 2018, higher blood BDNF levels. Neither abstract describes randomisation or blinding, and the 1997 control group was not concurrent-randomised, so these are counted as non-randomised human data. No placebo-controlled trial with a functional outcome was identified.", "citations": [ { "pmid": 11517472, "title": "[Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)].", "year": 1997, "finding": "Faster regression of neurological deficits reported in 30 patients with acute ischaemic stroke given semax with standard therapy than in 80 patients on standard therapy" }, { "doi": "10.17116/jnevro20181183261-68", "title": "The efficacy of semax in the tretament of patients at different stages of ischemic stroke", "year": 2018, "finding": "Higher plasma BDNF and better Barthel index scores reported in post-stroke patients given semax than in those not given it during rehabilitation" } ], "trials_query": "semax" }, { "indication": "Cognitive enhancement (memory, attention, focus)", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "Effects on learning and memory have been reported in rats, including counteracting heavy-metal-induced impairment of avoidance learning and altering spatial memory after prefrontal ischaemic lesions. No human trial measuring memory, attention or other cognitive performance was identified. One small placebo-controlled brain-imaging study in 24 healthy volunteers found a change in a resting-state brain network minutes after intranasal semax; it did not test cognitive performance and is not counted as an efficacy trial.", "citations": [ { "doi": "10.1134/S0012496616030066", "title": "Semax prevents learning and memory inhibition by heavy metals", "year": 2016, "finding": "Counteracted heavy-metal-induced inhibition of avoidance conditioning in rats" }, { "doi": "10.1007/s11055-009-9197-4", "title": "Formation of Spatial Memory in Rats with Ischemic Lesions to the Prefrontal Cortex; Effects of a Synthetic Analog of ACTH(4-7)", "year": 2009, "finding": "Effects on spatial memory formation in rats with prefrontal ischaemic lesions" }, { "doi": "10.1007/s10517-018-4234-3", "title": "Effects of Semax on the Default Mode Network of the Brain", "year": 2018, "finding": "Larger rostral default-mode-network component on resting-state fMRI in healthy volunteers after semax than after placebo; no cognitive outcome measured" } ], "trials_query": "semax" }, { "indication": "Anxiety", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "Anxiety-related findings are from rodents: in adolescent rats exposed to neonatal maternal deprivation, semax given in early life normalised measures of anxiety-like behaviour. No human study of semax for anxiety was identified.", "citations": [ { "doi": "10.1007/s10517-012-1574-2", "title": "Semax Attenuates the Influence of Neonatal Maternal Deprivation on the Behavior of Adolescent White Rats", "year": 2012, "finding": "Normalised anxiety-like behaviour in adolescent rats exposed to neonatal maternal deprivation" } ], "trials_query": "semax" } ], "safety": { "grade": "S4", "no_data_statement": true, "known_signals": [] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "No FDA-approved application: openFDA Drugs@FDA returns no application with a semax active ingredient (query: products.active_ingredients.name:SEMAX*). openFDA states its data are unvalidated.", "source_url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:SEMAX*", "source_title": "openFDA Drugs@FDA API (FDA)", "quote": "No matches found!", "retrieved": "2026-10-10" }, { "jurisdiction": "US", "status": "unapproved", "detail": "Semax (heptapeptide) appears on FDA's list of bulk drug substances previously in Category 2 (significant safety risks) of the compounding interim policy whose nominations were withdrawn by the nominators. FDA's safety statement remains on the page.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026)", "quote": "Compounded drugs containing semax (heptapeptide) may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation and peptide-related impurities. FDA has no, or limited, safety-related information for proposed routes of administration.", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "unapproved", "detail": "No product containing semax appears in EMA's downloadable medicines dataset (generated 10 Oct 2026), which covers centrally authorised medicines, refusals and withdrawn applications. National authorisations were not checked individually.", "source_url": "https://www.ema.europa.eu/en/medicines/download-medicine-data", "source_title": "Download medicine data | European Medicines Agency (EMA)", "quote": "This includes information on marketing authorisations of centrally authorised medicines and post-authorisation procedures.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "unapproved", "detail": "Queries of Health Canada's Drug Product Database API for the active ingredient and brand name semax returned no products on the retrieval date.", "source_url": "https://health-products.canada.ca/dpd-bdpp/?lang=eng", "source_title": "Drug Product Database online query", "quote": "Search by drug identification number", "retrieved": "2026-10-10" } ], "unknowns": [ "Sport status is not given: semax is not named on the 2026 WADA Prohibited List, and whether class S0 applies depends on whether any governmental health authority has approved it, which this record did not verify from a regulator source outside the tracked jurisdictions", "No randomised, blinded trial of semax in stroke with a functional outcome was identified", "No human trial of cognitive performance in healthy people was identified", "No systematic human safety data were identified; FDA states it has no, or limited, safety-related information for proposed routes and raises immunogenicity concerns", "Human pharmacokinetics after intranasal or injected use of non-pharmaceutical material are not characterised in the sources reviewed", "Status in the UK, Australia, Japan and China was not verified from regulator sources for this record" ], "mechanism": "Semax is a fragment-based analogue of ACTH; in rats it increased brain-derived neurotrophic factor (BDNF) levels and altered expression of neurotrophin and immune-related genes in the brain.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "sermorelin", "names": { "inn": "sermorelin", "common": [ "Sermorelin", "Sermorelin acetate", "GHRH(1-29)NH2", "GRF(1-29)" ], "codes": [], "brands": [], "cas": null }, "sequence": "YADAIFTNSYRKVLGQLSARKLLQDIMSR", "sequence_note": "Residues 1-29 of human growth hormone-releasing hormone with a C-terminal amide.", "class_by_jurisdiction": { "US": "C", "EU": null, "UK": null, "CA": "C", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic copy of the first 29 amino acids of human growth hormone-releasing hormone (GHRH). In the US it was approved as Geref, for testing pituitary growth hormone release (1990) and for idiopathic growth hormone deficiency in children (1997). The manufacturer discontinued Geref in 2008 and FDA withdrew both approvals in 2009; FDA later determined the withdrawal was not for safety or effectiveness reasons. No sermorelin product is currently approved in the US. It is offered by compounders and \"anti-ageing\" clinics for adult uses never tested in an approval trial.", "evidence": [ { "indication": "Idiopathic growth hormone deficiency in children (former US-approved use)", "tier": "E4", "human_rcts": null, "human_trials_any": null, "summary": "The principal published efficacy study was an open-label, uncontrolled multicentre study in 110 previously untreated prepubertal children with GH deficiency; mean height velocity rose over 12 months, and 74% were classed as good responders at 6 months. No randomised controlled trial against placebo or growth hormone was identified in this review. The product has not been marketed in the US since 2008.", "citations": [ { "doi": "10.1210/jcem.81.3.8772599", "title": "Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Geref International Study Group.", "year": 1996, "finding": "Mean height velocity increased over 12 months in an open-label study of 110 prepubertal GH-deficient children" } ], "trials_query": "sermorelin" }, { "indication": "Age-related decline in growth hormone, body composition and strength in older adults (anti-ageing claims)", "tier": "E4", "human_rcts": 0, "human_trials_any": 2, "summary": "Evidence is limited to very small, short studies in healthy older men, without a placebo group. In 10 older men, two weeks of GHRH(1-29) raised GH and IGF-1 to levels seen in young men (dose order randomised, no placebo). In 11 older men over six weeks, GH rose but IGF-1, body weight, muscle and fat by DEXA did not change; two of six strength measures improved. No trial has tested body composition, function, frailty or any clinical outcome against placebo. Trials of tesamorelin, a different GHRH analogue, are not evidence for sermorelin.", "citations": [ { "doi": "10.1210/jcem.75.2.1379256", "title": "Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men.", "year": 1992, "finding": "Raised 24-hour GH and IGF-1 over 14 days in 10 healthy older men" }, { "doi": "10.1016/s0026-0495(97)90174-8", "title": "Effects of single nightly injections of growth hormone—releasing hormone (GHRH 1–29) in healthy elderly men", "year": 1997, "finding": "Raised nocturnal GH without change in IGF-1, lean or fat mass over 6 weeks in 11 older men; 2 of 6 strength measures improved" } ], "trials_query": "sermorelin" } ], "safety": { "grade": "S3", "no_data_statement": true, "known_signals": [] }, "regulatory": [ { "jurisdiction": "US", "status": "withdrawn", "detail": "Geref (sermorelin acetate; NDA 19-863 diagnostic, approved 28 Dec 1990; NDA 20-443 for idiopathic GH deficiency in children, approved 26 Sept 1997; EMD Serono) was discontinued by the sponsor in 2008, and FDA withdrew approval of both NDAs effective 18 June 2009 at the sponsor's request. In 2013 FDA determined the products were not withdrawn for reasons of safety or effectiveness. Drugs@FDA lists both as Discontinued. Sermorelin does not appear in any category of FDA's 503A nominated bulk-substance list (updated 14 May 2026); this record does not determine whether compounding with it is lawful under another 503A pathway.", "source_url": "https://www.govinfo.gov/content/pkg/FR-2013-03-04/html/2013-04827.htm", "source_title": "Determination That GEREF (Sermorelin Acetate) Injection ... Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness (Federal Register, 4 March 2013)", "quote": "In the Federal Register of May 19, 2009 (74 FR 23407), FDA announced that it was withdrawing approval of NDA 19-863 and NDA 20-443, effective June 18, 2009.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "unapproved", "detail": "A query of Health Canada's Drug Product Database for the active ingredient sermorelin returned no products under any status (including cancelled products) on the retrieval date.", "source_url": "https://health-products.canada.ca/dpd-bdpp/?lang=eng", "source_title": "Drug Product Database online query", "quote": "Search by drug identification number", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S2.2.4", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "growth hormone-releasing hormone (GHRH) and its analogues (e.g. CJC-1293, CJC-1295, sermorelin and tesamorelin)" }, "trials": [], "unknowns": [ "No placebo-controlled trial of sermorelin in adults for body composition, strength, sleep, cognition or any other outcome claimed by anti-ageing clinics", "No long-term safety data in adults; the published adult studies lasted two to six weeks", "Quality and identity of compounded sermorelin are not covered by any current FDA approval", "Whether stimulating GH and IGF-1 over long periods in older adults alters cancer or metabolic risk has not been studied for sermorelin", "Post-marketing safety data from the Geref era are not published in a form that allows exposure-adjusted rates; FDA's 2013 notice reported only that its review found no safety reason for withdrawal", "EU, UK, Australian, Japanese and Chinese status (including any historic national authorisations) was not verified from regulator sources for this record" ], "mechanism": "Sermorelin binds pituitary GHRH receptors; in human studies it acutely and repeatedly increased growth hormone secretion.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "setmelanotide", "names": { "inn": "setmelanotide", "common": [ "Setmelanotide" ], "codes": [ "RM-493" ], "brands": [ "Imcivree" ], "cas": null }, "sequence": null, "sequence_note": "Cyclic octapeptide: Ac-Arg-cyclo[Cys-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 (disulfide between the two cysteines). Contains D-amino acids, so no plain one-letter sequence is given. Structure as described in the US prescribing information (chemical name: acetyl-L-arginyl-L-cysteinyl-D-alanyl-L-histidinyl-D-phenylalanyl-L-arginyl-L-tryptophanyl-L-cysteinamide cyclic (2-8)-disulfide).", "class_by_jurisdiction": { "US": "A", "EU": "A", "UK": "A", "CA": "A", "AU": "C", "JP": "A", "CN": null }, "what_it_is": "A synthetic cyclic peptide that activates the melanocortin-4 receptor, a brain receptor in the leptin-melanocortin pathway that regulates hunger. It is approved, under the brand Imcivree, only for specific rare forms of obesity: obesity due to POMC, PCSK1 or LEPR deficiency, Bardet-Biedl syndrome, and acquired hypothalamic obesity (approved in the US, EU, UK and Japan). The US label states it is not expected to be effective in general (polygenic) obesity.", "evidence": [ { "indication": "Obesity due to POMC, PCSK1 or LEPR deficiency", "tier": "E4", "human_rcts": 0, "human_trials_any": 3, "summary": "Evidence comes from two single-arm, open-label phase 3 trials (10 and 11 participants in the published full analysis sets) with a short blinded placebo-withdrawal sequence, and an earlier two-patient open-label report. Eight of 10 participants with POMC deficiency and 5 of 11 with LEPR deficiency reached at least 10% weight loss at about one year. There is no parallel-group randomised comparison, which is typical for ultra-rare conditions but limits the strength of inference.", "citations": [ { "doi": "10.1016/s2213-8587(20)30364-8", "title": "Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials", "year": 2020, "finding": "Weight loss of at least 10% at about one year in single-arm trials of people with POMC or LEPR deficiency obesity" }, { "doi": "10.1056/nejmoa1512693", "title": "Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist", "year": 2016, "finding": "Reduced hunger and substantial weight loss in two patients with POMC deficiency in an open-label study" } ], "trials_query": "setmelanotide" }, { "indication": "Obesity in Bardet-Biedl syndrome (and Alström syndrome)", "tier": "E3", "human_rcts": 1, "human_trials_any": 1, "summary": "One phase 3 trial (38 randomised) had a 14-week double-blind placebo-controlled period followed by 52 weeks of open-label treatment. Its primary endpoint was single-arm: 32.3% of patients aged 12 or older with Bardet-Biedl syndrome reached at least 10% weight reduction after 52 weeks. The randomised period was short and small, so the controlled evidence is limited. Alström syndrome was included in the trial but is not an approved indication.", "citations": [ { "doi": "10.1016/s2213-8587(22)00277-7", "title": "Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period", "year": 2022, "finding": "32.3% of patients aged 12 or older with Bardet-Biedl syndrome reached at least 10% weight reduction after 52 weeks" } ], "trials_query": "setmelanotide" }, { "indication": "Acquired hypothalamic obesity", "tier": "E2", "human_rcts": 1, "human_trials_any": 2, "summary": "An open-label phase 2 trial in 18 patients reported that 16 reached at least 5% BMI reduction at 16 weeks. A double-blind, placebo-controlled phase 3 trial (TRANSCEND, about 140 enrolled) has been presented as a conference abstract and its results are posted on ClinicalTrials.gov; a full peer-reviewed publication was not found on the retrieval date. By the retrieval date the indication was approved in the US (March 2026), Japan (August 2026), the EU and the UK.", "citations": [ { "doi": "10.1016/s2213-8587(24)00087-1", "title": "Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial", "year": 2024, "finding": "16 of 18 patients reached at least 5% BMI reduction after 16 weeks in an open-label trial" }, { "doi": "10.1093/ejendo/lvag096.414", "title": "P255 - ECE_1844 - Efficacy and safety of setmelanotide in acquired hypothalamic obesity: Results from a double-blind, multicentre, placebo-controlled, randomised phase 3 trial", "year": 2026, "finding": "Conference abstract reporting the randomised placebo-controlled phase 3 trial in acquired hypothalamic obesity" } ], "trials_query": "setmelanotide" } ], "safety": { "grade": "S2", "no_data_statement": true, "known_signals": [ { "signal": "Skin hyperpigmentation, darkening of pre-existing naevi and new melanocytic naevi", "evidence": "Listed in US prescribing information (Warnings and Precautions 5.4); skin hyperpigmentation is among the most common adverse reactions.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/213793s009lbl.pdf", "title": "IMCIVREE (setmelanotide) injection, for subcutaneous use" } }, { "signal": "Disturbance in sexual arousal, including spontaneous penile erection", "evidence": "US prescribing information, Warnings and Precautions 5.1; spontaneous penile erection listed among common adverse reactions.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/213793s009lbl.pdf", "title": "IMCIVREE (setmelanotide) injection, for subcutaneous use" } }, { "signal": "Depression and suicidal ideation", "evidence": "US prescribing information, Warnings and Precautions 5.2.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/213793s009lbl.pdf", "title": "IMCIVREE (setmelanotide) injection, for subcutaneous use" } }, { "signal": "Acute adrenal insufficiency and sodium imbalance in patients with acquired hypothalamic obesity", "evidence": "Added to US prescribing information in March 2026 (Warnings and Precautions 5.5 and 5.6).", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/213793s009lbl.pdf", "title": "IMCIVREE (setmelanotide) injection, for subcutaneous use" } }, { "signal": "Gastrointestinal effects (nausea, vomiting, diarrhoea, abdominal pain) and injection-site reactions", "evidence": "Most common adverse reactions in US prescribing information section 6.1.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/213793s009lbl.pdf", "title": "IMCIVREE (setmelanotide) injection, for subcutaneous use" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "approved", "detail": "NDA 213793 (Imcivree), original approval 25 November 2020; acquired hypothalamic obesity indication added by supplement 9 on 19 March 2026.", "source_url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/213793s009lbl.pdf", "source_title": "IMCIVREE prescribing information (FDA, revised 03/2026)", "quote": "IMCIVREE is a melanocortin 4 (MC4) receptor agonist indicated to reduce excess body weight and maintain reduction long term in adults and pediatric patients aged", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "approved", "detail": "Centrally authorised (EMEA product Imcivree), orphan medicine; marketing authorisation 16 July 2021. Current indications include acquired hypothalamic obesity, Bardet-Biedl syndrome and POMC (including PCSK1) or LEPR deficiency.", "source_url": "https://www.ema.europa.eu/en/medicines/human/EPAR/imcivree", "source_title": "Imcivree EPAR (EMA)", "quote": "Imcivree received a marketing authorisation valid throughout the EU on 16 July 2021.", "retrieved": "2026-10-10" }, { "jurisdiction": "UK", "status": "approved", "detail": "Great Britain marketing authorisation PLGB 55587/0001; SmPC retrieved from the MHRA products database (document dated 17 August 2026).", "source_url": "https://mhraproducts4853.blob.core.windows.net/docs/110c8f18603fd797b2354cf00e6c57dd510b48d3", "source_title": "IMCIVREE Summary of Product Characteristics (MHRA products database)", "quote": "IMCIVREE is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed Bardet Biedl syndrome (BBS) in adults and children 2 years of age and above.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "approved", "detail": "Drug Product Database: IMCIVREE, DIN 02537745, Rhythm Pharmaceuticals; status Marketed since 12 July 2023.", "source_url": "https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=102647", "source_title": "Health Canada Drug Product Database: IMCIVREE", "quote": "Current status: Marketed", "retrieved": "2026-10-10" }, { "jurisdiction": "AU", "status": "unapproved", "detail": "The TGA Product and Consumer Medicine Information repository returns no documents for setmelanotide. Absence of a PI/CMI is strong but not conclusive evidence of no ARTG registration; the ARTG search itself could not be loaded on the retrieval date.", "source_url": "https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=setmelanotide", "source_title": "TGA Product and Consumer Medicine Information search", "quote": "Trade Names and Active Ingredients containing setmelanotide . 0 Documents available.", "retrieved": "2026-10-10" }, { "jurisdiction": "JP", "status": "approved", "detail": "PMDA list of newly approved drugs, August 2026: Imcivree (Rhythm Pharma KK), setmelanotide acetate, approved 24 August 2026 as a new active ingredient for acquired hypothalamic obesity, orphan drug. Other indications are not approved in Japan per this list.", "source_url": "https://www.pmda.go.jp/files/000281578.xlsx", "source_title": "PMDA 承認品目一覧（新医薬品：2026年8月) (list linked from pmda.go.jp/review-services/drug-reviews/review-information/p-drugs/0040.html)", "quote": "後天性視床下部性肥満を効能・効果とする新有効成分含有医薬品", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "not_prohibited", "wada_class": null, "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "trials": [ { "nct": "NCT02896192", "title": "Setmelanotide for the Treatment of Early-Onset Pro-Opiomelanocortin (POMC) Deficiency Obesity", "phase": "3", "status": "Completed" }, { "nct": "NCT03287960", "title": "Setmelanotide for the Treatment of Leptin Receptor (LEPR) Deficiency Obesity", "phase": "3", "status": "Completed" }, { "nct": "NCT03746522", "title": "Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity", "phase": "3", "status": "Completed" }, { "nct": "NCT05774756", "title": "A Trial of Setmelanotide in Acquired Hypothalamic Obesity", "phase": "3", "status": "Active, not recruiting" }, { "nct": "NCT04725240", "title": "Open-Label Study of Setmelanotide in Hypothalamic Obesity", "phase": "2", "status": "Completed" } ], "unknowns": [ "No parallel-group randomised trial in POMC, PCSK1 or LEPR deficiency; efficacy rests on single-arm data in 21 people in the two pivotal trials", "Long-term (multi-year) outcomes beyond weight and hunger, such as cardiometabolic events, are not established", "Long-term consequences of persistent skin hyperpigmentation and new melanocytic naevi are not characterised", "Peer-reviewed full publication of the phase 3 acquired hypothalamic obesity trial was not found on the retrieval date", "Efficacy in general (polygenic) obesity is not established; the US label states it would not be expected to be effective" ], "mechanism": "Setmelanotide is an agonist of the melanocortin-4 (MC4) receptor, part of the hypothalamic leptin-melanocortin pathway that regulates hunger and energy expenditure; it is intended to act downstream of genetic or acquired defects in that pathway.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "survodutide", "names": { "inn": "survodutide", "common": [ "Survodutide" ], "codes": [ "BI 456906" ], "brands": [], "cas": "2805997-46-8" }, "sequence": null, "sequence_note": "Synthetic lipidated peptide; full structure not verified for this record.", "class_by_jurisdiction": { "US": "B", "EU": "B", "UK": "B", "CA": "B", "AU": "B", "JP": "B", "CN": "B" }, "what_it_is": "An investigational synthetic peptide from Boehringer Ingelheim that activates the glucagon and GLP-1 receptors. It is in phase 3 development for obesity and for metabolic dysfunction-associated steatotic liver disease, including steatohepatitis with fibrosis or cirrhosis. It is not approved in any jurisdiction checked.", "evidence": [ { "indication": "Weight reduction in obesity or overweight", "tier": "E1", "human_rcts": null, "human_trials_any": null, "summary": "Two published phase 3 trials and one phase 2 trial. SYNCHRONIZE-1 (725 adults without diabetes, 76 weeks): weight change -12.2% and -13.0% in the two dose groups versus -5.4% with placebo. SYNCHRONIZE-2 (752 adults with type 2 diabetes, 76 weeks): -8.2% and -9.8% versus -3.9%. The phase 2 trial (387 adults, 46 weeks) reported -6.2% to -14.9% versus -2.8%, with only 60% completing treatment.", "citations": [ { "doi": "10.1056/nejmoa2600751", "title": "Survodutide Once Weekly for the Treatment of Adults with Obesity", "year": 2026, "finding": "SYNCHRONIZE-1: weight change -12.2% and -13.0% vs -5.4% with placebo at 76 weeks" }, { "doi": "10.1056/nejmoa2607219", "title": "Survodutide Once Weekly in Adults with Obesity and Type 2 Diabetes", "year": 2026, "finding": "SYNCHRONIZE-2: weight change -8.2% and -9.8% vs -3.9% with placebo at 76 weeks in obesity with type 2 diabetes" }, { "doi": "10.1016/S2213-8587(23)00356-X", "title": "Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial", "year": 2024, "finding": "Phase 2: weight change -6.2% to -14.9% vs -2.8% with placebo at 46 weeks" } ], "trials_query": "survodutide AND obesity" }, { "indication": "Liver fat in obesity with metabolic dysfunction-associated steatotic liver disease (MASLD)", "tier": "E2", "human_rcts": null, "human_trials_any": null, "summary": "One phase 3 trial (SYNCHRONIZE-MASLD, 216 adults, 48 weeks). A reduction of at least 30% in MRI-measured liver fat occurred in 68.5% with survodutide versus 28.6% with placebo (treatment-regimen estimand). Liver fat is an imaging surrogate; the authors note short duration and recruitment limited to the US and Spain.", "citations": [ { "doi": "10.1038/s41591-026-04479-3", "title": "Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial", "year": 2026, "finding": "At least 30% liver-fat reduction in 68.5% vs 28.6% with placebo at 48 weeks (treatment-regimen estimand)" } ], "trials_query": "survodutide AND liver" }, { "indication": "Metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis", "tier": "E3", "human_rcts": null, "human_trials_any": null, "summary": "One phase 2 biopsy trial (293 treated participants, 48 weeks). MASH improvement without worsening fibrosis occurred in 43% to 62% across dose groups versus 14% with placebo; fibrosis improvement by at least one stage in 34% to 36% versus 22%. Phase 3 histology and outcome trials (LIVERAGE, LIVERAGE-Cirrhosis) are recruiting.", "citations": [ { "doi": "10.1056/NEJMoa2401755", "title": "A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis", "year": 2024, "finding": "MASH improvement without fibrosis worsening 43-62% vs 14% with placebo (phase 2)" } ], "trials_query": "survodutide AND steatohepatitis" } ], "safety": { "grade": "S2", "no_data_statement": true, "known_signals": [ { "signal": "Gastrointestinal adverse events", "evidence": "In SYNCHRONIZE-1, gastrointestinal adverse events occurred in 80.9% and 89.7% of the two survodutide groups versus 47.9% with placebo.", "citation": { "doi": "10.1056/nejmoa2600751", "title": "Survodutide Once Weekly for the Treatment of Adults with Obesity" } }, { "signal": "High treatment discontinuation in dose-finding", "evidence": "In the phase 2 obesity trial, 61% of survodutide recipients completed the 46-week treatment period (60% on placebo); gastrointestinal adverse events occurred in 75% versus 42%.", "citation": { "doi": "10.1016/S2213-8587(23)00356-X", "title": "Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "investigational", "detail": "No Drugs@FDA application found for survodutide (openFDA Drugs@FDA query by active ingredient returns no records). Phase 3 trials sponsored by Boehringer Ingelheim are registered on ClinicalTrials.gov.", "source_url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:survodutide", "source_title": "openFDA Drugs@FDA API query: active ingredient survodutide", "quote": "\"code\": \"NOT_FOUND\", \"message\": \"No matches found!\"", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "investigational", "detail": "Survodutide does not appear in the EMA medicines dataset (2,748 records of centrally processed medicines, timestamp 2026-10-10).", "source_url": "https://www.ema.europa.eu/en/documents/report/medicines-output-medicines_json-report_en.json", "source_title": "EMA medicines data (JSON report)", "quote": "\"total_records\": 2748, \"timestamp\": \"2026-10-10T06:02:36Z\"", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "investigational", "detail": "Health Canada Drug Product Database active-ingredient query for survodutide returns an empty result.", "source_url": "https://health-products.canada.ca/api/drug/activeingredient/?lang=en&type=json&ingredientname=survodutide", "source_title": "Health Canada Drug Product Database API: active ingredient survodutide", "quote": "[]", "retrieved": "2026-10-10" }, { "jurisdiction": "AU", "status": "investigational", "detail": "TGA Product Information repository search for survodutide returns no documents.", "source_url": "https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=PI&q=survodutide", "source_title": "TGA eBS - Product and Consumer Medicine Information (search: survodutide)", "quote": "Search PI Trade Names and Active Ingredients containing survodutide . 0 Documents available.", "retrieved": "2026-10-10" }, { "jurisdiction": "JP", "status": "investigational", "detail": "Survodutide does not appear in the PMDA List of Approved Products (New Drugs), which covers approvals through February 2026; later approvals would not be shown. A Japanese phase 3 trial (NCT06176365) is completed.", "source_url": "https://www.pmda.go.jp/files/000281190.pdf", "source_title": "PMDA List of Approved Products: New Drugs (April 2004 to February 2026)", "quote": "April 2004 to February 2026", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S0", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development" }, "trials": [ { "nct": "NCT06066515", "title": "A Study to Test Whether Survodutide (BI 456906) Helps People Living With Overweight or Obesity Who do Not Have Diabetes to Lose Weight", "phase": "3", "status": "Completed" }, { "nct": "NCT06066528", "title": "A Study to Test Whether Survodutide (BI 456906) Helps People Living With Overweight or Obesity Who Also Have Diabetes to Lose Weight", "phase": "3", "status": "Completed" }, { "nct": "NCT06077864", "title": "A Study to Test the Effect of Survodutide (BI 456906) on Cardiovascular Safety in People With Overweight or Obesity (SYNCHRONIZE™ - CVOT)", "phase": "3", "status": "Completed" }, { "nct": "NCT06309992", "title": "A Study to Test Whether Survodutide Helps People Living With Obesity or Overweight and With a Confirmed or Presumed Liver Disease Called Non-alcoholic Steatohepatitis (NASH) to Reduce Liver Fat and to Lose Weight (SYNCHRONIZE-MASLD)", "phase": "3", "status": "Completed" }, { "nct": "NCT06176365", "title": "A Study to Test Whether Survodutide Helps Japanese People Living With Obesity Disease", "phase": "3", "status": "Completed" }, { "nct": "NCT06214741", "title": "A Study to Test Whether Survodutide (BI 456906) Helps Chinese People Living With Overweight or Obesity to Lose Weight", "phase": "3", "status": "Completed" }, { "nct": "NCT06632444", "title": "LIVERAGE™: A Study to Test Whether Survodutide Helps People With a Liver Disease Called NASH/MASH Who Have Moderate or Advanced Liver Fibrosis", "phase": "3", "status": "Recruiting" }, { "nct": "NCT06632457", "title": "LIVERAGE™ - Cirrhosis: A Study to Test Whether Survodutide Helps People With a Liver Disease Called NASH/MASH Who Have Cirrhosis", "phase": "3", "status": "Recruiting" }, { "nct": "NCT04771273", "title": "A Study to Test Safety and Efficacy of Survodutide (BI456906) in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3)", "phase": "2", "status": "Completed" }, { "nct": "NCT04667377", "title": "A Study to Test Whether Different Doses of BI 456906 Help People With Overweight or Obesity to Lose Weight", "phase": "2", "status": "Completed" } ], "unknowns": [ "Cardiovascular safety result: SYNCHRONIZE-CVOT (NCT06077864) is completed on ClinicalTrials.gov but no publication was located as of 2026-10-10", "Whether liver-fat and histology improvements translate into fewer cirrhosis or liver-related events; LIVERAGE trials are recruiting", "Safety beyond 76 weeks of exposure, the longest duration in published phase 3 trials", "Effects of glucagon receptor agonism on heart rate, lean mass and amino-acid metabolism over the long term in humans", "Identity and purity of any material sold outside trials; no lawful supply exists and no assay data were located" ], "mechanism": "Survodutide is a peptide agonist of both the glucagon receptor and the GLP-1 receptor.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "tb-500", "names": { "inn": null, "common": [ "TB-500", "TB500", "Thymosin beta-4 fragment (LKKTETQ)", "Ac-LKKTETQ" ], "codes": [], "brands": [], "cas": null }, "sequence": "LKKTETQ", "sequence_note": "Seven residues corresponding to positions 17-23 of mature thymosin beta-4 (the actin-binding region). An anti-doping analysis identified the N-terminally acetylated form (Ac-LKKTETQ) in a product sold as TB-500; FDA names the substance 'thymosin beta-4, fragment (LKKTETQ), also known as TB-500'. The content of other products sold under this name was not assessed.", "class_by_jurisdiction": { "US": "C", "EU": null, "UK": null, "CA": null, "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic seven-amino-acid fragment of thymosin beta-4, a 43-residue protein found in most human cells. It is often marketed as if it were thymosin beta-4 itself, with claims of faster recovery from tendon, ligament and muscle injuries and wound healing. Research on the full-length protein does not transfer automatically to the fragment. TB-500 is not approved as a medicine in any jurisdiction checked. FDA states it has identified no human exposure data for it, and the World Anti-Doping Agency names it as prohibited.", "evidence": [ { "indication": "Injury recovery: tendon, ligament, muscle and skin wounds (TB-500 fragment itself)", "tier": "E6", "human_rcts": 0, "human_trials_any": 0, "summary": "The only efficacy study of the fragment identified was in mice: the synthetic seven-residue peptide LKKTETQ gave dermal wound-repair results in aged mice comparable to full-length thymosin beta-4. No study of the fragment in tendon, ligament or muscle injury models was identified. No published human trial of TB-500 exists. A phase 1/2 trial of the fragment for cardiovascular biomarkers was registered in China in 2026 and is recruiting, with no results; it does not address injury recovery.", "citations": [ { "doi": "10.1046/j.1524-475x.2003.11105.x", "title": "Thymosin β4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice", "year": 2003, "finding": "The synthetic fragment LKKTETQ increased dermal wound closure in aged mice to a degree comparable with full-length thymosin beta-4" } ], "trials_query": "TB-500" }, { "indication": "Chronic skin wounds and ulcers (full-length thymosin beta-4, not TB-500)", "tier": "E3", "human_rcts": 1, "human_trials_any": null, "summary": "This row concerns full-length thymosin beta-4, a different molecule from TB-500, and is shown because marketing cites this research. A double-blind, placebo-controlled, dose-escalation phase 2 trial of topical thymosin beta-4 in 73 patients with venous leg ulcers across eight European sites reported safety comparable to placebo; the efficacy findings were described only as suggestive, and no confirmatory trial was identified. No trial has tested injected full-length thymosin beta-4 for tendon, ligament or muscle injury.", "citations": [ { "doi": "10.1111/j.1749-6632.2010.05490.x", "title": "The effect of thymosin treatment of venous ulcers", "year": 2010, "finding": "Topical full-length thymosin beta-4 was tolerated similarly to placebo in 73 patients with venous ulcers; efficacy reported as suggestive, not confirmed" }, { "doi": "10.1046/j.1523-1747.1999.00708.x", "title": "Thymosin β4 Accelerates Wound Healing", "year": 1999, "finding": "Full-length thymosin beta-4 increased wound re-epithelialisation and contraction in a rat full-thickness wound model" } ], "trials_query": "thymosin beta 4" } ], "safety": { "grade": "S5", "no_data_statement": true, "known_signals": [] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "Not approved: FDA has approved no product containing TB-500. FDA's list of bulk substances that may present significant safety risks names 'Thymosin beta-4, fragment (LKKTETQ), also known as TB-500' among substances previously in 503A Category 2 whose nominations were withdrawn; it is not on the current 503A Category 1 or 2 lists (updated 14 May 2026). FDA cites possible immunogenicity due to aggregation and peptide-related impurities.", "source_url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "source_title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (FDA, content current as of 04/22/2026)", "quote": "FDA has not identified any human exposure data drug products containing Thymosin Beta-4, Fragment. FDA lacks important information regarding any safety issues raised by this drug, including whether it would cause harm if administered to humans.", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S2.3", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Thymosin-ß4 and its derivatives e.g. TB-500" }, "trials": [ { "nct": "NCT07487363", "title": "TB-500 (Thymosin Beta 4 17-23 Fragment) for Cardiovascular Biomarkers in Stable ASCVD", "phase": "1/2", "status": "Recruiting" } ], "unknowns": [ "No published human data on TB-500 of any kind: no pharmacokinetics, no safety and no efficacy by any route", "No study of the fragment in tendon, ligament or muscle injury models was identified; claims for these uses rest on extrapolation from the full-length protein or from skin wounds in mice", "Immunogenicity is unassessed; FDA states compounded TB-500 may pose a risk of immunogenicity due to aggregation and peptide-related impurities", "What products sold as TB-500 actually contain (the acetylated fragment, the free fragment, full-length thymosin beta-4 or other material) was not assessed for this record", "Regulatory status outside the US was not verified from regulator sources for this record" ], "mechanism": "TB-500 corresponds to the actin-binding region of thymosin beta-4, a protein that sequesters monomeric actin inside cells; in aged mice the free fragment increased dermal wound closure.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "teriparatide", "names": { "inn": "teriparatide", "common": [ "Teriparatide", "PTH(1-34)", "rhPTH(1-34)", "Parathyroid hormone (1-34)" ], "codes": [], "brands": [ "Forteo", "Forsteo", "Bonsity", "Movymia", "Terrosa", "Livogiva", "Sondelbay", "Kauliv", "Teriparatide SUN", "Zandoriah", "Osnuvo" ], "cas": null }, "sequence": "SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF", "sequence_note": "Identical to the 34 N-terminal residues of the 84-residue human parathyroid hormone; Forteo is produced in a recombinant Escherichia coli strain (US label, section 11).", "class_by_jurisdiction": { "US": "A", "EU": "A", "UK": null, "CA": "A", "AU": null, "JP": "A", "CN": null }, "what_it_is": "A 34-amino-acid fragment of human parathyroid hormone, the region responsible for its biological activity. It is an approved prescription medicine for osteoporosis in the US, EU, Canada and Japan, sold originally as Forteo (Forsteo in the EU) and now also as several follow-on and biosimilar products. Unlike most osteoporosis drugs, which slow bone breakdown, it is classed as a bone-forming (anabolic) agent. Regulatory status in the UK, Australia and China was not verified for this record.", "evidence": [ { "indication": "Postmenopausal osteoporosis (fracture prevention)", "tier": "E1", "human_rcts": 2, "human_trials_any": null, "summary": "Two large randomised controlled trials with fracture endpoints support this approved indication. In the pivotal placebo-controlled trial of 1,637 postmenopausal women with prior vertebral fracture, teriparatide reduced new vertebral and nonvertebral fragility fractures and increased bone mineral density. In VERO, a double-blind trial of 1,360 women with severe osteoporosis, new vertebral fractures were less frequent with teriparatide than with the active comparator risedronate. Reduction of hip fracture has not been demonstrated (EMA product overview).", "citations": [ { "doi": "10.1056/NEJM200105103441904", "title": "Effect of Parathyroid Hormone (1-34) on Fractures and Bone Mineral Density in Postmenopausal Women with Osteoporosis", "year": 2001, "finding": "Reduced new vertebral and nonvertebral fragility fractures versus placebo in postmenopausal women with prior vertebral fracture" }, { "doi": "10.1016/S0140-6736(17)32137-2", "title": "Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial", "year": 2018, "finding": "New vertebral fractures in 5.4% with teriparatide versus 12.0% with risedronate over 24 months in women with severe osteoporosis" } ], "trials_query": "teriparatide" }, { "indication": "Osteoporosis in men", "tier": "E2", "human_rcts": 1, "human_trials_any": null, "summary": "One randomised placebo-controlled trial in 437 men with low bone density showed increased spine and hip bone mineral density. Its endpoint was bone density, not fracture; the trial was stopped early, after a median of about 11 months, because of the rat osteosarcoma finding. The US label accordingly describes the male indication as increasing bone mass, not reducing fractures.", "citations": [ { "doi": "10.1359/jbmr.2003.18.1.9", "title": "The Effect of Teriparatide [Human Parathyroid Hormone (1–34)] Therapy on Bone Density in Men With Osteoporosis", "year": 2003, "finding": "Increased lumbar spine and femoral neck bone mineral density versus placebo in men with osteoporosis" } ], "trials_query": "teriparatide AND male osteoporosis" }, { "indication": "Glucocorticoid-induced osteoporosis", "tier": "E2", "human_rcts": 1, "human_trials_any": null, "summary": "One randomised double-blind trial of 428 adults on long-term glucocorticoids compared teriparatide with alendronate. Lumbar spine bone mineral density rose more with teriparatide (primary endpoint), and fewer new vertebral fractures were recorded in the teriparatide group (a secondary outcome); serum calcium elevations were more common with teriparatide. No placebo-controlled fracture trial exists in this population.", "citations": [ { "doi": "10.1056/NEJMoa071408", "title": "Teriparatide or Alendronate in Glucocorticoid-Induced Osteoporosis", "year": 2007, "finding": "Greater increase in lumbar spine bone mineral density with teriparatide than with alendronate in glucocorticoid-treated adults" } ], "trials_query": "teriparatide AND glucocorticoid" }, { "indication": "Acceleration of fracture healing (off-label claim)", "tier": "E3", "human_rcts": 0, "human_trials_any": null, "summary": "Not an approved use. In a randomised double-blind trial of 102 postmenopausal women with distal radius fractures, the prespecified primary comparison (higher-dose teriparatide versus placebo) showed no difference in time to radiographic healing; a shorter healing time in the lower-dose arm came from a post hoc analysis that the authors said should be interpreted with caution. No adequately powered trial has shown faster fracture healing.", "citations": [ { "doi": "10.1359/jbmr.090731", "title": "Teriparatide for acceleration of fracture repair in humans: A prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures", "year": 2010, "finding": "Primary hypothesis (shorter time to cortical bridging with the higher-dose arm versus placebo) not supported in women with distal radial fractures" } ], "trials_query": "teriparatide AND fracture healing" } ], "safety": { "grade": "S1", "no_data_statement": false, "known_signals": [ { "signal": "Osteosarcoma in rats", "evidence": "Long-term treatment of F344 rats produced bone neoplasms, including osteosarcoma, with incidence dependent on dose and treatment duration. The US label retains an osteosarcoma warning and states there are limited data on risk beyond 2 years of use.", "citation": { "doi": "10.1080/01926230490462138", "title": "Bone Neoplasms in F344 Rats Given Teriparatide [rhPTH(1-34)] Are Dependent on Duration of Treatment and Dose" } }, { "signal": "Osteosarcoma in humans: no increase detected in surveillance", "evidence": "A 15-year US postmarketing surveillance study found adult osteosarcoma incidence among teriparatide users no different from the expected background rate. The current US label states that osteosarcoma has been reported post-marketing but an increased risk has not been observed in human observational studies; it carries no boxed warning.", "citation": { "doi": "10.1002/jbmr.4188", "title": "Teriparatide Did Not Increase Adult Osteosarcoma Incidence in a 15-Year US Postmarketing Surveillance Study" } }, { "signal": "Hypercalcaemia, hypersensitivity reactions, cutaneous calcification and urolithiasis risk", "evidence": "Listed in Warnings and Precautions of the current US label (revised 08/2026), which added hypersensitivity reactions as a recent major change.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/021318Orig1s059lbl.pdf", "title": "FORTEO (teriparatide injection) Prescribing Information" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "approved", "detail": "Approved under NDA 021318 (Forteo, Eli Lilly; original approval 26 Nov 2002). Drugs@FDA also lists Bonsity (NDA 211939), a teriparatide product under NDA 218771, and generic teriparatide ANDAs (Teva, Apotex, Amphastar). Label indications: postmenopausal osteoporosis at high fracture risk, increasing bone mass in men with primary or hypogonadal osteoporosis, and glucocorticoid-associated osteoporosis.", "source_url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/021318Orig1s059lbl.pdf", "source_title": "FORTEO (teriparatide injection) Prescribing Information, revised 08/2026", "quote": "FORTEO is a parathyroid hormone analog, (PTH 1-34), indicated for:", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "approved", "detail": "Centrally authorised as Forsteo since 10 June 2003. The EMA medicines dataset also lists authorised teriparatide products Movymia, Terrosa, Livogiva, Sondelbay, Kauliv, Teriparatide SUN and Zandoriah; Qutavina was withdrawn after authorisation.", "source_url": "https://www.ema.europa.eu/en/medicines/human/EPAR/forsteo", "source_title": "Forsteo | European Medicines Agency (EMA)", "quote": "This medicine is authorised for use in the European Union", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "approved", "detail": "Health Canada Drug Product Database lists teriparatide products including TEVA-TERIPARATIDE INJECTION (DIN 02486423, Marketed), OSNUVO (DIN 02495589, Marketed) and APO-TERIPARATIDE INJECTION (DIN 02498804, Marketed). FORTEO (DIN 02254689) is listed as Cancelled Post Market (24 Feb 2026).", "source_url": "https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=97663", "source_title": "Drug Product Database: TEVA-TERIPARATIDE INJECTION", "quote": "Current status: Marketed", "retrieved": "2026-10-10" }, { "jurisdiction": "JP", "status": "approved", "detail": "PMDA's English review-report index lists Forteo, teriparatide (genetical recombination), approved July 2010. Other Japanese teriparatide products were not verified for this record.", "source_url": "https://www.pmda.go.jp/english/review-services/reviews/approved-information/drugs/0001.html", "source_title": "Review Reports: Drugs | PMDA", "quote": "Forteo Teriparatide (genetical recombination) July 2010", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "not_prohibited", "wada_class": null, "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "trials": [ { "nct": "NCT00670501", "title": "Effects of Teriparatide in the Treatment of Postmenopausal Women With Osteoporosis", "phase": "3", "status": "Completed" }, { "nct": "NCT01709110", "title": "VERtebral Fracture Treatment Comparisons in Osteoporotic Women", "phase": "4", "status": "Completed" }, { "nct": "NCT00051558", "title": "Comparison of Teriparatide With Alendronate for Treating Glucocorticoid-Induced Osteoporosis", "phase": "3", "status": "Completed" } ], "unknowns": [ "Osteosarcoma risk with use beyond 2 years: the US label states data are limited", "Hip fracture reduction has not been demonstrated in randomised trials (EMA product overview)", "No fracture-endpoint randomised trial in men; the male indication rests on bone density", "No adequately powered randomised evidence that it speeds healing of acute fractures", "Teriparatide is not named on the 2026 WADA Prohibited List; whether anti-doping authorities would treat it under a catch-all clause was not assessed", "Regulatory status in the UK, Australia and China was not verified from regulator sources for this record" ], "mechanism": "Teriparatide binds the same cell-surface receptors as endogenous parathyroid hormone in bone and kidney; intermittent exposure in clinical trials increased markers of bone formation and bone mineral density.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "tesamorelin", "names": { "inn": "tesamorelin", "common": [ "Tesamorelin", "Tesamorelin acetate", "TH9507" ], "codes": [ "TH9507" ], "brands": [ "Egrifta", "Egrifta SV", "Egrifta WR" ], "cas": null }, "sequence": null, "sequence_note": "The full 44-residue sequence of human growth hormone-releasing factor (GHRH 1-44) with a trans-3-hexenoyl group attached to the N-terminal tyrosine (US label, section 11). Left null because of the N-terminal acylation.", "class_by_jurisdiction": { "US": "A", "EU": "C", "UK": null, "CA": "C", "AU": null, "JP": null, "CN": null }, "what_it_is": "A synthetic, chemically stabilised version of human growth hormone-releasing hormone (GHRH). It is approved in the US only for reducing excess abdominal fat in adults with HIV and lipodystrophy; the US label states it is not indicated for weight loss. An EU marketing application was withdrawn in 2012, and its Canadian product listing was cancelled in 2022. It is also offered outside its label for fat loss, body composition, cognition and \"anti-ageing\".", "evidence": [ { "indication": "Excess abdominal (visceral) fat in adults with HIV-associated lipodystrophy", "tier": "E1", "human_rcts": 2, "human_trials_any": null, "summary": "Two randomised placebo-controlled trials (412 and 404 participants) found that tesamorelin reduced CT-measured visceral fat over 26 weeks (about 15% and 11% versus small changes on placebo), with improvements in some lipid measures and raised IGF-1. In the extension phase, visceral fat returned toward baseline after switching to placebo. Neither trial measured cardiovascular events; the US label states long-term cardiovascular safety is not established, and the EMA's committee questioned whether the fat reduction was clinically meaningful.", "citations": [ { "doi": "10.1056/NEJMoa072375", "title": "Metabolic Effects of a Growth Hormone–Releasing Factor in Patients with HIV", "year": 2007, "finding": "Visceral adipose tissue fell 15.2% with tesamorelin versus a 5.0% rise with placebo over 26 weeks in 412 adults with HIV" }, { "doi": "10.1097/QAI.0b013e3181cbdaff", "title": "Effects of Tesamorelin, a Growth Hormone–Releasing Factor, in HIV-Infected Patients With Abdominal Fat Accumulation: A Randomized Placebo-Controlled Trial With a Safety Extension", "year": 2010, "finding": "Visceral fat fell 10.9% versus 0.6% on placebo at 6 months; gains were lost after switching to placebo" }, { "doi": "10.1097/QAD.0b013e32830a5058", "title": "Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation", "year": 2008, "finding": "26-week re-randomised extension of the first Phase 3 trial reporting longer-term safety and visceral fat effects in adults with HIV" } ], "trials_query": "tesamorelin" }, { "indication": "Fatty liver (NAFLD) in people with HIV", "tier": "E3", "human_rcts": 0, "human_trials_any": 2, "summary": "Two small randomised placebo-controlled trials in people with HIV (50 and 61 participants) found reductions in liver fat; the larger trial's primary endpoint was a 4.1 percentage-point absolute reduction in hepatic fat fraction over 12 months. Neither was powered for liver-related clinical outcomes, and the authors called for further studies of long-term histological effects. Not an approved indication.", "citations": [ { "doi": "10.1016/S2352-3018(19)30338-8", "title": "Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial", "year": 2019, "finding": "Greater reduction in hepatic fat fraction than placebo over 12 months in 61 adults with HIV and NAFLD" }, { "doi": "10.1001/jama.2014.8334", "title": "Effect of Tesamorelin on Visceral Fat and Liver Fat in HIV-Infected Patients With Abdominal Fat Accumulation", "year": 2014, "finding": "Reduced visceral fat and modestly reduced liver fat over 6 months versus placebo in 50 adults with HIV" } ], "trials_query": "tesamorelin AND fatty liver" }, { "indication": "Visceral fat and cardiometabolic markers in people without HIV (abdominal obesity)", "tier": "E3", "human_rcts": 0, "human_trials_any": 1, "summary": "One randomised placebo-controlled trial of 60 abdominally obese adults selected for reduced growth hormone secretion found lower visceral fat, triglycerides, C-reactive protein and carotid intima-media thickness after 12 months, with no change in subcutaneous fat. No trial has tested it in obesity without that selection, and none measured clinical outcomes. The US label states it is not indicated for weight loss and has a weight-neutral effect.", "citations": [ { "doi": "10.1210/jc.2012-2794", "title": "Metabolic Effects of a Growth Hormone-Releasing Factor in Obese Subjects with Reduced Growth Hormone Secretion: A Randomized Controlled Trial", "year": 2012, "finding": "Reduced visceral adipose tissue versus placebo over 12 months in 60 abdominally obese adults with reduced GH secretion" } ], "trials_query": "tesamorelin AND obesity" }, { "indication": "Cognition in older adults and mild cognitive impairment", "tier": "E3", "human_rcts": 0, "human_trials_any": 1, "summary": "One randomised placebo-controlled trial of 152 adults aged 55 to 87 (66 with mild cognitive impairment) reported a favourable effect on a cognitive composite after 20 weeks, driven mainly by executive function. Adverse events were reported by 68% on tesamorelin versus 36% on placebo. The result has not been replicated in a larger or longer trial, and no dementia or functional outcomes were assessed.", "citations": [ { "doi": "10.1001/archneurol.2012.1970", "title": "Effects of Growth Hormone–Releasing Hormone on Cognitive Function in Adults With Mild Cognitive Impairment and Healthy Older Adults", "year": 2012, "finding": "Favourable effect on a cognitive composite versus placebo over 20 weeks in older adults with and without mild cognitive impairment" } ], "trials_query": "tesamorelin AND cognition" } ], "safety": { "grade": "S2", "no_data_statement": false, "known_signals": [ { "signal": "Glucose intolerance or diabetes, fluid retention (oedema, arthralgia, carpal tunnel syndrome), hypersensitivity reactions, raised IGF-1", "evidence": "Listed in Warnings and Precautions of the current US label, which also contraindicates use with active malignancy and states the effects of prolonged IGF-1 elevation are unknown.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/022505s020lbl.pdf", "title": "EGRIFTA WR (tesamorelin) for injection Prescribing Information" } }, { "signal": "Anti-drug antibodies", "evidence": "The US label reports anti-tesamorelin IgG antibodies in about half of trial patients at 26 and 52 weeks, with cross-reactivity to endogenous GHRH in about 60% of antibody-positive patients.", "citation": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/022505s020lbl.pdf", "title": "EGRIFTA WR (tesamorelin) for injection Prescribing Information" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "approved", "detail": "Approved 10 Nov 2010 (Theratechnologies; originally NDA 022505, deemed a BLA on 23 March 2020). Current formulations are Egrifta SV and Egrifta WR, which the label states are not substitutable. Indication limited to reduction of excess abdominal fat in HIV-infected adults with lipodystrophy. Not on any 503A bulk-substance category list (FDA list updated 14 May 2026).", "source_url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/022505s020lbl.pdf", "source_title": "EGRIFTA WR (tesamorelin) for injection Prescribing Information, revised 3/2025", "quote": "EGRIFTA WR is a growth hormone-releasing factor (GHRF) analog indicated for the reduction of excess abdominal fat in HIV", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "unapproved", "detail": "Not authorised. The marketing application (Ferrer Internacional) was withdrawn on 21 June 2012; at that point the CHMP's provisional opinion was that it could not have been approved, citing doubts about clinical meaningfulness of the fat reduction, applicability to European patients and IGF-1 elevation.", "source_url": "https://www.ema.europa.eu/en/medicines/human/EPAR/egrifta", "source_title": "Egrifta: withdrawn application | European Medicines Agency (EMA)", "quote": "the CHMP had some concerns and was of the provisional opinion that Egrifta could not have been approved for the treatment of excess abdominal fat in HIV patients with lipodystrophy.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "withdrawn", "detail": "Health Canada's Drug Product Database lists EGRIFTA (DIN 02438712, first marketed 23 June 2015) as Cancelled Post Market since 30 Sept 2022; a second EGRIFTA listing (DIN 02423677) is Cancelled Pre Market. No other tesamorelin product was found in the database.", "source_url": "https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=92311", "source_title": "Drug Product Database: EGRIFTA (DIN 02438712)", "quote": "Current status: Cancelled Post Market Current status date: 2022-09-30", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "prohibited", "wada_class": "S2.2.4", "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "growth hormone-releasing hormone (GHRH) and its analogues (e.g. CJC-1293, CJC-1295, sermorelin and tesamorelin)" }, "trials": [ { "nct": "NCT00123253", "title": "TH9507 in Patients With HIV-Associated Lipodystrophy", "phase": "3", "status": "Completed" }, { "nct": "NCT00608023", "title": "TH9507 Extension Study in Patients With HIV-Associated Lipodystrophy", "phase": "3", "status": "Completed" }, { "nct": "NCT02196831", "title": "Tesamorelin Effects on Liver Fat and Histology in HIV", "phase": "NA", "status": "Completed" }, { "nct": "NCT00675506", "title": "Effectiveness of Growth Hormone Releasing Hormone in Reducing Abdominal Fat in People Who Are Obese", "phase": "2", "status": "Completed" }, { "nct": "NCT00257712", "title": "SMART: Somatotrophics, Memory, and Aging Research Trial", "phase": "2", "status": "Completed" } ], "unknowns": [ "Long-term cardiovascular safety has not been established (US label limitation of use)", "Whether visceral fat reduction translates into fewer cardiovascular, liver or metabolic clinical events has not been tested", "The effects of prolonged IGF-1 elevation are unknown (US label)", "No randomised trial in people without HIV beyond a single 60-person trial in obese adults with reduced GH secretion", "A long-term post-marketing observational study (NCT01579695) was terminated; no results were identified", "Regulatory status in the UK, Australia, Japan and China was not verified from regulator sources for this record" ], "mechanism": "Tesamorelin binds pituitary GHRH receptors; in clinical trials it increased growth hormone and IGF-1 concentrations and reduced CT-measured visceral fat.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "thymosin-alpha-1", "names": { "inn": "thymalfasin", "common": [ "Thymosin alpha-1", "Thymosin α1", "Ta1", "Tα1", "Thymalfasin" ], "codes": [], "brands": [ "Zadaxin" ], "cas": null }, "sequence": "SDAAVDTSSEITTKDLKEKKEVVEEAEN", "sequence_note": "28 residues with an acetylated N-terminal serine; corresponds to residues 2-29 of human prothymosin alpha (UniProt P06454).", "class_by_jurisdiction": { "US": "C", "EU": null, "UK": null, "CA": null, "AU": null, "JP": null, "CN": null }, "what_it_is": "A 28-amino-acid peptide originally isolated from thymus tissue, made synthetically as thymalfasin (brand Zadaxin). It is an approved prescription medicine in some countries, mainly for chronic hepatitis B and as an immune adjunct, but is not approved in the United States. FDA states it is not approved in the US, Japan or Europe except Italy. In the US it is sold through compounding and gray-market channels with claims for viral infections, chronic fatigue, Lyme disease, cancer and general immune support.", "evidence": [ { "indication": "Chronic hepatitis B", "tier": "E3", "human_rcts": null, "human_trials_any": null, "summary": "Several small randomised trials, mostly from the 1990s, gave mixed results. A Taiwanese trial of 98 patients reported higher combined viral clearance at 18 months with a 26-week course than with no treatment. A US phase 3 double-blind placebo-controlled trial of 97 patients did not show a statistically significant difference. A meta-analysis of four small trials against interferon alpha found responses accumulated after treatment ended. FDA's 2024 review judged the evidence insufficient, noting outdated comparators and assays; none of the trials tested current standard antivirals as comparators.", "citations": [ { "doi": "10.1002/hep.510270527", "title": "Efficacy of thymosin α1 in patients with chronic hepatitis B: A randomized, controlled trial", "year": 1998, "finding": "Higher complete virological response at 18 months than untreated controls in 98 patients with chronic hepatitis B" }, { "doi": "10.1046/j.1365-2893.1999.00181.x", "title": "Thymosin α1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo-controlled study", "year": 1999, "finding": "Complete response 14% versus 4% with placebo in 97 patients, not statistically significant; authors state results do not confirm earlier reports" }, { "doi": "10.1016/j.antiviral.2007.10.014", "title": "Comparison of the efficacy of thymosin alpha-1 and interferon alpha in the treatment of chronic hepatitis B: A meta-analysis", "year": 2008, "finding": "Across four small randomised trials (199 patients), responses were not better than interferon alpha at end of treatment but higher six months after treatment" } ], "trials_query": "thymosin alpha 1 hepatitis B" }, { "indication": "Chronic hepatitis C", "tier": "E3", "human_rcts": 2, "human_trials_any": null, "summary": "A randomised, double-blind, placebo-controlled trial in 552 patients who had not responded to earlier interferon-based therapy found no difference in sustained viral response when thymosin alpha-1 was added to peginterferon and ribavirin (12.7% versus 10.5%); a higher rate appeared only in a subgroup completing all 48 weeks. A small earlier placebo-controlled pilot reported no viral clearance. These trials used older interferon regimens, not current direct-acting antivirals.", "citations": [ { "doi": "10.1111/j.1365-2893.2011.01524.x", "title": "Thymosin alpha-1 with peginterferon alfa-2a/ribavirin for chronic hepatitis C not responsive to IFN/ribavirin: an adjuvant role?", "year": 2012, "finding": "No difference in sustained viral response versus placebo in the intention-to-treat population of 552 patients" } ], "trials_query": "thymosin alpha 1 hepatitis C" }, { "indication": "Sepsis", "tier": "E3", "human_rcts": 2, "human_trials_any": null, "summary": "The largest trial, TESTS (1,106 adults with sepsis in 22 Chinese centres, double-blind, placebo-controlled), found no difference in 28-day mortality (23.4% versus 24.1%). An earlier single-blind randomised trial (ETASS, 361 patients) reported lower 28-day mortality with a marginal p-value. The randomised evidence is therefore conflicting, and the larger, better-blinded trial was negative. All trials were conducted in China.", "citations": [ { "doi": "10.1136/bmj-2024-082583", "title": "The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial", "year": 2025, "finding": "No difference in 28-day all-cause mortality versus placebo in 1,089 analysed adults with sepsis" }, { "doi": "10.1186/cc11932", "title": "The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial", "year": 2013, "finding": "28-day mortality 26.0% versus 35.0% in 361 patients with severe sepsis, marginal statistical significance" } ], "trials_query": "thymosin alpha 1 sepsis" }, { "indication": "COVID-19", "tier": "E4", "human_rcts": null, "human_trials_any": null, "summary": "Evidence comes mainly from retrospective cohort studies early in the pandemic. A meta-analysis pooling eight studies reported lower mortality with marked heterogeneity and no difference in need for mechanical ventilation or length of stay; its authors called for randomised trials. FDA's 2024 review noted that three of four meta-analyses found no mortality reduction and judged the information insufficient.", "citations": [ { "doi": "10.1007/s10787-023-01354-2", "title": "The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression", "year": 2023, "finding": "Pooled data from eight mostly non-randomised studies associated treatment with lower mortality (high heterogeneity), with no difference in ventilation need or hospital stay" } ], "trials_query": "thymosin alpha 1 COVID-19" }, { "indication": "Cancer (adjunct to chemotherapy; metastatic melanoma as the main tested setting)", "tier": "E3", "human_rcts": 1, "human_trials_any": null, "summary": "A randomised trial in 488 patients with metastatic melanoma compared dacarbazine plus interferon alpha with arms adding thymosin alpha-1. More tumour responses were seen in two thymosin arms, but the differences in overall and progression-free survival did not reach statistical significance. FDA's 2024 review of liver and lung cancer studies found small randomised trials, single-arm and retrospective studies, and concluded the evidence was insufficient. These regimens are not current standard care.", "citations": [ { "doi": "10.1200/JCO.2009.25.5208", "title": "Large Randomized Study of Thymosin α 1, Interferon Alfa, or Both in Combination With Dacarbazine in Patients With Metastatic Melanoma", "year": 2010, "finding": "More tumour responses with thymosin alpha-1 arms in 488 patients with metastatic melanoma; survival differences not statistically significant" } ], "trials_query": "thymosin alpha 1 cancer" }, { "indication": "Chronic fatigue syndrome (ME/CFS)", "tier": "E8", "human_rcts": 0, "human_trials_any": 0, "summary": "FDA's 2024 review for the Pharmacy Compounding Advisory Committee found no clinical studies of thymosin alpha-1 in ME/CFS and no data supporting effectiveness. No animal model study for this claim was identified in this review.", "citations": [], "trials_query": "thymosin alpha 1 chronic fatigue" } ], "safety": { "grade": "S2", "no_data_statement": false, "known_signals": [] }, "regulatory": [ { "jurisdiction": "US", "status": "unapproved", "detail": "Not approved: FDA states it has approved no drug product containing thymosin alpha-1, and that it is not approved in the US, Japan or Europe except Italy. A nomination for the 503A bulks list was withdrawn; FDA reviewed it at its own discretion for the 4 December 2024 Pharmacy Compounding Advisory Committee and concluded the evaluation criteria weigh against adding it. FDA's safety-risks page lists Ta1 among substances previously in Category 2 whose nominations were withdrawn; it is not on the current Category 1 or 2 lists (updated 14 May 2026).", "source_url": "https://www.fda.gov/media/183892/download", "source_title": "Thymosin Alpha-1 (Ta1) Related Bulk Drug Substances (FDA presentation, Pharmacy Compounding Advisory Committee, December 4, 2024)", "quote": "Ta1 is not approved in the United States, Japan, or Europe (except Italy)", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "not_prohibited", "wada_class": null, "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" }, "trials": [ { "nct": "NCT02867267", "title": "The Efficacy and Safety of Ta1 for Sepsis", "phase": "3", "status": "Completed" }, { "nct": "NCT00711620", "title": "Efficacy of Thymosin alpha1 for Severe Sepsis", "phase": null, "status": "Completed" } ], "unknowns": [ "Approval status in China, Italy and other countries where it is reportedly marketed was not verified from those regulators' own sources; FDA states it cannot independently verify the claimed approvals in all countries", "Immunogenicity of the 28-residue peptide is not characterised; FDA notes possible aggregation at higher concentrations", "Safety in haematopoietic stem cell transplant recipients is uncertain; FDA raised concern about graft-versus-host disease or engraftment failure", "No randomised trial compares thymosin alpha-1 with current standard antivirals for hepatitis B or C", "Claims for Lyme disease, allergies, asthma, psoriatic arthritis and general immune support were not tiered here; no controlled human study for them was identified in this review", "Not named on the 2026 WADA Prohibited List; S0 covers only substances with no current approval anywhere, and FDA reports approval in Italy, but WADA's own classification of this peptide was not confirmed" ], "mechanism": "Thymosin alpha-1 is an immunomodulatory peptide whose effects are attributed in part to interaction with Toll-like receptor 9 on dendritic and lymphoid progenitor cells.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" }, { "slug": "tirzepatide", "names": { "inn": "tirzepatide", "common": [ "Tirzepatide" ], "codes": [ "LY3298176" ], "brands": [ "Mounjaro", "Zepbound" ], "cas": "2023788-19-2" }, "sequence": null, "sequence_note": "Synthetic peptide containing non-coded amino acids and a fatty diacid side chain; not representable as a plain one-letter sequence.", "class_by_jurisdiction": { "US": "A", "EU": "A", "UK": "A", "CA": "A", "AU": "A", "JP": "A", "CN": null }, "what_it_is": "A synthetic peptide that activates the receptors for two gut hormones, GIP and GLP-1. It is an approved prescription medicine for type 2 diabetes (Mounjaro) and for chronic weight management (Zepbound in the US and Japan; Mounjaro carries the weight indication in the UK). The UK MHRA has reported falsified Mounjaro pens in circulation. Status in China was not verified for this record.", "evidence": [ { "indication": "Type 2 diabetes: glycaemic control and cardiovascular outcomes", "tier": "E1", "human_rcts": null, "human_trials_any": null, "summary": "Supported by the phase 3 SURPASS programme. In SURPASS-2 (1,879 participants on metformin), all tirzepatide doses lowered HbA1c more than semaglutide (differences -0.15 to -0.45 percentage points). In SURPASS-CVOT (13,299 participants with atherosclerotic cardiovascular disease), tirzepatide was non-inferior to dulaglutide for major cardiovascular events (12.2% vs 13.1%, hazard ratio 0.92); superiority was not shown.", "citations": [ { "doi": "10.1056/NEJMoa2107519", "title": "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes", "year": 2021, "finding": "HbA1c reduction superior to semaglutide at all three tirzepatide doses in type 2 diabetes on metformin" }, { "doi": "10.1056/nejmoa2505928", "title": "Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes", "year": 2025, "finding": "Major cardiovascular events 12.2% vs 13.1% with dulaglutide (HR 0.92; non-inferior, not superior)" } ], "trials_query": "tirzepatide AND type 2 diabetes" }, { "indication": "Chronic weight management (obesity or overweight)", "tier": "E1", "human_rcts": null, "human_trials_any": null, "summary": "Multiple large randomised trials (SURMOUNT programme). In SURMOUNT-1 (2,539 adults without diabetes), mean weight change at week 72 ranged from -15.0% to -20.9% across dose groups versus -3.1% with placebo. In SURMOUNT-5 (751 adults without diabetes), weight change at week 72 was -20.2% with tirzepatide versus -13.7% with semaglutide. Gastrointestinal events were the most common adverse events in SURMOUNT-5.", "citations": [ { "doi": "10.1056/NEJMoa2206038", "title": "Tirzepatide Once Weekly for the Treatment of Obesity", "year": 2022, "finding": "Mean weight change -15.0% to -20.9% vs -3.1% with placebo at week 72" }, { "doi": "10.1056/NEJMoa2416394", "title": "Tirzepatide as Compared with Semaglutide for the Treatment of Obesity", "year": 2025, "finding": "Weight change -20.2% vs -13.7% with semaglutide at week 72 in adults with obesity without diabetes" } ], "trials_query": "tirzepatide AND obesity" }, { "indication": "Obstructive sleep apnoea with obesity", "tier": "E1", "human_rcts": null, "human_trials_any": null, "summary": "Two randomised placebo-controlled phase 3 trials reported together (SURMOUNT-OSA, 469 participants). The apnoea-hypopnoea index fell by 25.3 and 29.3 events per hour with tirzepatide versus 5.3 and 5.5 with placebo at week 52 (treatment differences about -20 and -24 events per hour).", "citations": [ { "doi": "10.1056/NEJMoa2404881", "title": "Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity", "year": 2024, "finding": "AHI reduced by about 20-24 more events per hour than placebo at week 52 in two trials" } ], "trials_query": "tirzepatide AND sleep apnea" }, { "indication": "Heart failure with preserved ejection fraction and obesity", "tier": "E2", "human_rcts": null, "human_trials_any": null, "summary": "One phase 3 trial (SUMMIT, 731 patients, median follow-up 104 weeks). Cardiovascular death or worsening heart failure occurred in 9.9% with tirzepatide versus 15.3% with placebo (hazard ratio 0.62). The difference was driven by worsening heart-failure events; cardiovascular deaths were few (8 vs 5) and did not differ.", "citations": [ { "doi": "10.1056/NEJMoa2410027", "title": "Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity", "year": 2025, "finding": "Composite of cardiovascular death or worsening heart failure 9.9% vs 15.3% (HR 0.62)" } ], "trials_query": "tirzepatide AND heart failure" }, { "indication": "Metabolic dysfunction-associated steatohepatitis (MASH)", "tier": "E3", "human_rcts": null, "human_trials_any": null, "summary": "One phase 2 trial (SYNERGY-NASH, 190 participants, 157 with evaluable week 52 biopsies). MASH resolution without worsening fibrosis occurred in 44% to 62% across tirzepatide dose groups versus 10% with placebo. No phase 3 histology or liver-outcomes result has been published.", "citations": [ { "doi": "10.1056/NEJMoa2401943", "title": "Tirzepatide for Metabolic Dysfunction–Associated Steatohepatitis with Liver Fibrosis", "year": 2024, "finding": "MASH resolution 44-62% vs 10% with placebo at week 52 (phase 2)" } ], "trials_query": "tirzepatide AND steatohepatitis" } ], "safety": { "grade": "S1", "no_data_statement": false, "known_signals": [ { "signal": "Gastrointestinal adverse events", "evidence": "Gastrointestinal events were the most common adverse events in SURMOUNT-5, mostly mild to moderate. SURPASS-CVOT reported more gastrointestinal adverse events with tirzepatide than dulaglutide. The UK MHRA strengthened warnings on acute pancreatitis for GLP-1 and dual GIP/GLP-1 receptor agonists in January 2026.", "citation": { "doi": "10.1056/nejmoa2505928", "title": "Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes" } }, { "signal": "Gallbladder and biliary disease (incretin-class signal)", "evidence": "Meta-analysis of GLP-1 receptor agonist trials found increased gallbladder or biliary disease (RR 1.37); tirzepatide was not part of that analysis, so the class finding is indirect for this compound.", "citation": { "doi": "10.1001/jamainternmed.2022.0338", "title": "Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases" } }, { "signal": "Thyroid C-cell tumours in rodents (GLP-1 receptor agonist class)", "evidence": "GLP-1 receptor agonists cause thyroid C-cell proliferation in rodents; human relevance is not established.", "citation": { "doi": "10.1210/en.2009-1272", "title": "Glucagon-Like Peptide-1 Receptor Agonists Activate Rodent Thyroid C-Cells Causing Calcitonin Release and C-Cell Proliferation" } } ] }, "regulatory": [ { "jurisdiction": "US", "status": "approved", "detail": "Drugs@FDA NDA 215866 (Mounjaro, Eli Lilly), original approval 05/13/2022 as a new molecular entity. Zepbound is NDA 217806 (approved 11/08/2023).", "source_url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=215866", "source_title": "Drugs@FDA: FDA-Approved Drugs, NDA 215866", "quote": "05/13/2022 ORIG-1 Approval Type 1 - New Molecular Entity PRIORITY", "retrieved": "2026-10-10" }, { "jurisdiction": "EU", "status": "approved", "detail": "Centrally authorised as Mounjaro on 15 September 2022.", "source_url": "https://www.ema.europa.eu/en/medicines/human/EPAR/mounjaro", "source_title": "Mounjaro | European Medicines Agency (EPAR)", "quote": "Mounjaro received a marketing authorisation valid throughout the EU on 15 September 2022.", "retrieved": "2026-10-10" }, { "jurisdiction": "UK", "status": "approved", "detail": "MHRA press release of 8 November 2023 authorising a weight-management indication for Mounjaro, which it describes as already used for type 2 diabetes.", "source_url": "https://www.gov.uk/government/news/mhra-authorises-diabetes-drug-mounjaro-tirzepatide-for-weight-management-and-weight-loss", "source_title": "MHRA authorises diabetes drug Mounjaro (tirzepatide) for weight management and weight loss", "quote": "The Medicines and Healthcare products Regulatory Agency (MHRA) has today (8 November 2023) authorised via a national application route, a new indication for the diabetes medicine, Mounjaro (tirzepatide), for weight loss and weight management in adults aged 18 and over.", "retrieved": "2026-10-10" }, { "jurisdiction": "CA", "status": "approved", "detail": "Health Canada Drug Product Database, Mounjaro (drug code 102190), status Approved, 2022-11-24.", "source_url": "https://health-products.canada.ca/api/drug/status/?lang=en&type=json&id=102190", "source_title": "Health Canada Drug Product Database API: status, drug code 102190 (Mounjaro)", "quote": "\"drug_code\":102190,\"status\":\"Approved\",\"history_date\":\"2022-11-24\"", "retrieved": "2026-10-10" }, { "jurisdiction": "AU", "status": "approved", "detail": "TGA Product Information repository lists a PI for Mounjaro (tirzepatide). The main TGA ARTG search (tga.gov.au) timed out on retrieval.", "source_url": "https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=PI&q=tirzepatide", "source_title": "TGA eBS - Product and Consumer Medicine Information (search: tirzepatide)", "quote": "Search PI Trade Names and Active Ingredients containing tirzepatide . 1 Documents available.", "retrieved": "2026-10-10" }, { "jurisdiction": "JP", "status": "approved", "detail": "PMDA List of Approved Products (New Drugs): Mounjaro approved Sep. 26, 2022 as a new active ingredient for type 2 diabetes; Zepbound approved Dec. 27, 2024 for obesity (restricted to patients with hypertension, dyslipidaemia or type 2 diabetes meeting BMI criteria).", "source_url": "https://www.pmda.go.jp/files/000281190.pdf", "source_title": "PMDA List of Approved Products: New Drugs (April 2004 to February 2026)", "quote": "Drugs with a new active ingredient indicated for the treatment of type 2 diabetes mellitus.", "retrieved": "2026-10-10" } ], "sport": { "wada_status": "not_prohibited", "wada_class": null, "source_url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "quote": "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development" }, "trials": [ { "nct": "NCT03987919", "title": "A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes", "phase": "3", "status": "Completed" }, { "nct": "NCT04255433", "title": "A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes", "phase": "3", "status": "Completed" }, { "nct": "NCT04184622", "title": "A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight", "phase": "3", "status": "Completed" }, { "nct": "NCT05822830", "title": "A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities", "phase": "3", "status": "Completed" }, { "nct": "NCT04847557", "title": "A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial", "phase": "3", "status": "Completed" }, { "nct": "NCT04166773", "title": "A Study of Tirzepatide (LY3298176) in Participants With Nonalcoholic Steatohepatitis (NASH)", "phase": "2", "status": "Completed" } ], "unknowns": [ "Effect on cardiovascular death and hard outcomes in obesity without diabetes; no placebo-controlled outcome trial in that population has reported in a publication located for this record", "Whether MASH histology improvements seen in a 190-participant phase 2 trial translate into fewer cirrhosis or liver-related events", "Safety beyond the roughly two to three years covered by published randomised trials, including long-term gallbladder, pancreatic and thyroid outcomes", "Separate contribution of GIP receptor agonism versus GLP-1 receptor agonism to the effects seen in humans", "Content and purity of compounded or unlicensed tirzepatide products; falsified pens have been reported by the MHRA but systematic assay data are lacking" ], "mechanism": "Tirzepatide is a single peptide that acts as an agonist at both the GIP and GLP-1 receptors. A fatty-acid side chain binds albumin and prolongs its duration of action.", "reviewer": "OSMF research team (AI-assisted, source-verified)", "last_reviewed": "2026-10-10" } ] }