Summary
Hydrochlorothiazide has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Obesity would be drug repurposing rather than first-in-human development. This does not mean it is approved for Obesity. ClinicalTrials.gov lists 8 registered trials linking Hydrochlorothiazide to Obesity: 1 is currently recruiting; 6 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00239538). It plans or enrolled 840 participants. Registration activity spans 2003 to 2017. The literature layer holds 11 publications for this pair: 5 Cochrane reviews, 1 randomised controlled trial publication and 5 clinical trial publications. Publication years run from 2011 to 2025. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Obesity ranks 368 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: Sustained weight loss of >5% without intervention: ~5-10% at 2 years; weight regain almost universal after behavioural intervention alone (95% return to within 5% of starting weight at 5 years on lifestyle alone).
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 79.0 (trials 29.0, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 1 recruiting, 0 active / not yet recruiting, 6 completed, 1 other |
| Linked publications | 11 (5 Cochrane reviews, 5 clinical trial publications, 1 randomised controlled trial publication) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | DGIdb |
| Linked via biomarker / target | FTO |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT00775814 | Efficacy of Candesartan on Reducing Blood Pressure in Insulin-Resistant, Obese Patients With Hypertension. 2006 | completed | Phase 4 | 188 |
| NCT00239538 | SMOOTH - Blood Pressure Control in Diabetic/Obese Patients 2003 | completed | Phase 4 | 840 |
| NCT00987662 | Irbesartan Versus Amlodipine: The OBI Study 2012 | withdrawn | Phase 4 | — |
| NCT00459056 | The Vascular Effects of Carvedilol Controlled Release (CR) in Abdominally Obese Hypertensive Patients 2007 | completed | Phase 3 | 25 |
| NCT00289887 | Obese Hypertension Study (0954-315) 2006 | completed | Phase 3 | 261 |
| NCT00871871 | Multiple Dose Effects of Hydrochlorothiazide and Isosorbide Mononitrate on Glucose Homeostasis (MK-0000-117)(Completed) 2009 | completed | Phase 1 | 64 |
| NCT03006796 | Observational Study of Azilsartan/Chlorthalidone and Irbesartan/Hydrochlorothiazide in Hypertension and Obesity. 2017 | completed | Not applicable | 94 |
| NCT03476551 | Bariatric Surgery and Pharmacokinetics of Hydrochlorothiazide 2016 | recruiting | Not applicable | 12 |
Published literature
- Clinical trial publication Effects of a polypill on circulating levels of resistin and visfatin in men with non-alcoholic fatty liver disease: A five-year clinical trialNazari-Robati M, Dehesh T, Shahouzehi B et al. · PloS one · 2025 · PMID 41060939
- Clinical trial publication Efficacy and Safety of Firibastat, A First-in-Class Brain Aminopeptidase A Inhibitor, in Hypertensive Overweight Patients of Multiple Ethnic OriginsFerdinand KC, Balavoine F, Besse B et al. · Circulation · 2019 · PMID 31014072
- Cochrane review Comparative Efficacy of Antihypertensive Agents in Salt-Sensitive Hypertensive Patients: A Network Meta-AnalysisQi H, Liu Z, Cao H et al. · American journal of hypertension · 2018 · PMID 29438454
- Cochrane review Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statementPaz MA, de-La-Sierra A, Sáez M et al. · Medicine · 2016 · PMID 27472680
- Clinical trial publication Efficacy and tolerability of triple-combination therapy with olmesartan, amlodipine, and hydrochlorothiazide: a subgroup analysis of patients stratified by hypertension severity, age, sex, and obesityKreutz R, Ammentorp B, Laeis P et al. · Journal of clinical hypertension (Greenwich, Conn.) · 2014 · PMID 25243781
- Cochrane review Cochrane in context: pharmacological interventions for hypertension in childrenChaturvedi S, Lipszyc DH, Licht C et al. · Evidence-based child health : a Cochrane review journal · 2014 · PMID 25236306
- Cochrane review Pharmacological interventions for hypertension in childrenChaturvedi S, Lipszyc DH, Licht C et al. · Evidence-based child health : a Cochrane review journal · 2014 · PMID 25236305
- Cochrane review Pharmacological interventions for hypertension in childrenChaturvedi S, Lipszyc DH, Licht C et al. · The Cochrane database of systematic reviews · 2014 · PMID 24488616
- Clinical trial publication Differential effects of renin-angiotensin-aldosterone system inhibition, sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension: a double-blind, placebo-controlled cross-over trialDorresteijn JA, Schrover IM, Visseren FL et al. · Journal of hypertension · 2013 · PMID 23235355
- Randomized controlled trial Aliskiren-based dual- and triple-combination therapies in high-risk US minority patients with stage 2 hypertensionFerdinand KC, Weitzman R, Purkayastha D et al. · Journal of the American Society of Hypertension : JASH · 2012 · PMID 22305998
- Clinical trial publication Efficacy and safety of early versus late titration of fixed-dose irbesartan/hydrochlorothiazide: ACTUAL studyGirerd X, Rosenbaum D, Aoun J et al. · Blood pressure. Supplement · 2011 · PMID 22352122
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target FTO. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Hydrochlorothiazide approved for Obesity?
Hydrochlorothiazide has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Obesity would be drug repurposing rather than first-in-human development. This does not mean it is approved for Obesity. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Hydrochlorothiazide in clinical trials for Obesity?
ClinicalTrials.gov lists 8 registered trials linking Hydrochlorothiazide to Obesity: 1 is currently recruiting; 6 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00239538). It plans or enrolled 840 participants. Registration activity spans 2003 to 2017.
What does the evidence show for Hydrochlorothiazide in Obesity?
Hydrochlorothiazide has both completed registered trials and synthesis-level publications linked to Obesity. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target FTO. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.