Muscarinic Receptor Antagonist Improves Nerve Fiber Function in Subjects with Type 2 Diabetes and Peripheral Neuropathy

Degeneration of nerve fibers due to diabetic peripheral neuropathy (DPN) has been linked to mitochondrial dysfunction. Manipulation of mitochondrial dysfunction through antagonism of muscarinic receptors (MR) promotes neurite outgrowth in adult sensory neurons in vitro and provides neuroprotection in rodent models of DPN. The aim of the study was to assess the efficacy of MR antagonist topical 3% oxybutynin in structural and functional measures of nerve fiber function in subjects with type 2 diabetes (T2DM) and DPN. Pilot, randomized, placebo-controlled, double-blinded study in 40 subjects assessed at baseline and after 20 weeks of treatment with oxybutynin or placebo with the following: intraepidermal nerve fiber density (IENFD) on proximal and distal leg; neuropathy scores and quality of life (Norfolk QoL DN) questionnaire. Baseline demographic characteristics were similar between the treatment groups. IENFD improved significantly after 20 weeks for the treatment group. Neuropathy scores and Norfolk QoL DN also improved significantly in the treatment group (Table 1). No improvements were seen in the placebo group. In this study, oxybutynin proves to be efficacious in improving structural and functional measures of small fiber function, and quality of life in T2DM subjects. These results offer a promising novel therapeutic approach for DPN that needs to be explored further.