A muscarinic receptor antagonist reverses multiple indices of diabetic peripheral neuropathy: preclinical and clinical studies using oxybutynin.
Level 2 - randomized trial
Individual randomized double-blind placebo-controlled clinical trial supported by preclinical models
PubMed 38526612 · doi:10.1007/s00401-024-02710-4
What was done
Preclinical studies tested oxybutynin (1–100 nmol/l) on neuritogenesis and mitochondrial energetics in adult rat and streptozotocin (STZ)-diabetic mouse sensory neuron cultures. In vivo studies evaluated systemic (3–10 mg/kg/day s.c.) and topical (3% gel daily for up to 8 weeks) oxybutynin on sensory hypoalgesia, allodynia, and corneal/skin nerve loss in STZ-diabetic rodents and db/db mice. In a randomized, double-blind, placebo-controlled clinical trial (NCT03050827), human subjects with type 2 diabetes and confirmed peripheral neuropathy received daily topical 3% oxybutynin gel or placebo for 6 months. The primary endpoint was change in intra-epidermal nerve fibre density (IENFD) in skin biopsies at 20 weeks; secondary endpoints included clinical neuropathy, pain, and quality of life scores.
What was found
No quantitative values, effect sizes, or exact p-values were reported in the abstract. Preclinically, oxybutynin improved neurite outgrowth, mitochondrial respiration, paw heat hypoalgesia, paw tactile allodynia, and skin/corneal nerve profile loss. In the human trial, topical 3% oxybutynin met the primary endpoint by significantly increasing IENFD compared to placebo, and demonstrated significant improvements in secondary clinical neuropathy, pain, and quality of life scores.
Why it matters
Repurposing topical oxybutynin may provide a disease-modifying, regenerative therapeutic strategy addressing both structural nerve loss and functional symptoms in diabetic peripheral neuropathy.
Limits
The abstract provides no sample size (n) for the human trial or preclinical cohorts, nor any numerical values, confidence intervals, or safety and tolerability data. The study is described as proof-of-concept and requires confirmation in larger phase 3 cohorts.
Cited by
- supports In a clinical trial in diabetic patients with neuropathy, topical oxybutynin significantly promoted nerve regrowth in the skin compared to placebo.