Summary
Epalrestat has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Peripheral Neuropathy (Diabetic Peripheral Neuropathy) would be drug repurposing rather than first-in-human development. This does not mean it is approved for Peripheral Neuropathy (Diabetic Peripheral Neuropathy). ClinicalTrials.gov lists 3 registered trials linking Epalrestat to Peripheral Neuropathy (Diabetic Peripheral Neuropathy): 1 is currently recruiting; 1 is active or not yet recruiting; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT05184049). The largest enrolment is 120 participants (NCT06201611). Registration activity spans 2022 to 2024. The literature layer holds 8 publications for this pair: 1 Cochrane review, 2 randomised controlled trial publications and 5 clinical trial publications. Publication years run from 2001 to 2018. 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 Diabetic Neuropathy ranks 186 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: Progressive with worsening glycaemic control; reversal essentially not possible with current treatments once established; spontaneous improvement only in cases of rapid glycaemic normalisation early in course.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 50.0 (trials 9.0, literature 21.0, tier 15, approved bonus 5.0) |
| Registered trials | 3 total: 1 recruiting, 1 active / not yet recruiting, 0 completed, 1 other |
| Linked publications | 8 (5 clinical trial publications, 2 randomised controlled trial publications, 1 Cochrane review) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | inhibitor |
| Data sources | DGIdb |
| Linked via biomarker / target | AKR1B1 |
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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT05184049 | Effects of Epalrestat on Peripheral Neuropathy and Central Nervous System in Diabetic Patients 2022 | status unknown | Phase 4 | 72 |
| NCT06330233 | Different Amounts of Moxibustion in the Treatment of DPN: A Clinical RCT Study 2024 | active, not recruiting | Not applicable | 90 |
| NCT06201611 | Evaluating a Nitric Oxide Generator, Nebivolol as a Disease Modifier in Patients With Diabetic Neuropathy. 2024 | recruiting | PHASE2, PHASE3 | 120 |
Published literature
- Cochrane review Efficacy of epalrestat plus α-lipoic acid combination therapy versus monotherapy in patients with diabetic peripheral neuropathy: a meta-analysis of 20 randomized controlled trialsZhao M, Chen JY, Chu YD et al. · Neural regeneration research · 2018 · PMID 29926837
- Clinical trial publication Effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy in patients with type 2 diabetes, in relation to suppression of N(ɛ)-carboxymethyl lysineKawai T, Takei I, Tokui M et al. · Journal of diabetes and its complications · 2010 · PMID 19716319
- Clinical trial publication Stratified analyses for selecting appropriate target patients with diabetic peripheral neuropathy for long-term treatment with an aldose reductase inhibitor, epalrestatHotta N, Kawamori R, Atsumi Y et al. · Diabetic medicine : a journal of the British Diabetic Association · 2008 · PMID 18644069
- Clinical trial publication Erythrocyte sorbitol level as a predictor of the efficacy of epalrestat treatment for diabetic peripheral polyneuropathyAndo H, Takamura T, Nagai Y et al. · Journal of diabetes and its complications · 2006 · PMID 17070440
- Clinical trial publication Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy: the 3-year, multicenter, comparative Aldose Reductase Inhibitor-Diabetes Complications TrialHotta N, Akanuma Y, Kawamori R et al. · Diabetes care · 2006 · PMID 16801576
- Clinical trial publication Aldose reductase inhibition alters nodal Na+ currents and nerve conduction in human diabeticsMisawa S, Kuwabara S, Kanai K et al. · Neurology · 2006 · PMID 16717216
- Randomized controlled trial Fidarestat (SNK-860), a potent aldose reductase inhibitor, normalizes the elevated sorbitol accumulation in erythrocytes of diabetic patientsAsano T, Saito Y, Kawakami M et al. · Journal of diabetes and its complications · 2002 · PMID 12039395
- Randomized controlled trial Aldose reductase inhibition ameliorates pupillary light reflex and F-wave latency in patients with mild diabetic neuropathyNakayama M, Nakamura J, Hamada Y et al. · Diabetes care · 2001 · PMID 11375376
Mechanism and notes
Recorded mechanism or class: inhibitor.
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 AKR1B1. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Epalrestat approved for Peripheral Neuropathy (Diabetic Peripheral Neuropathy)?
Epalrestat has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Peripheral Neuropathy (Diabetic Peripheral Neuropathy) would be drug repurposing rather than first-in-human development. This does not mean it is approved for Peripheral Neuropathy (Diabetic Peripheral Neuropathy). Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Epalrestat in clinical trials for Peripheral Neuropathy (Diabetic Peripheral Neuropathy)?
ClinicalTrials.gov lists 3 registered trials linking Epalrestat to Peripheral Neuropathy (Diabetic Peripheral Neuropathy): 1 is currently recruiting; 1 is active or not yet recruiting; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT05184049). The largest enrolment is 120 participants (NCT06201611). Registration activity spans 2022 to 2024.
What does the evidence show for Epalrestat in Peripheral Neuropathy (Diabetic Peripheral Neuropathy)?
Trials of Epalrestat in Peripheral Neuropathy (Diabetic Peripheral Neuropathy) are registered but none has completed, so there is no outcome evidence from those studies yet; the record is a signal of research interest. 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 AKR1B1. 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.