5 Neuroprotective effects of metformin in diabetic peripheral neuropathy

BackgroundDiabetic peripheral neuropathy (DPN) affects around 50% of the 500 million persons with type 2 diabetes worldwide and is considered disabling and irreversible. Currently no treatment for DPN is available and previous studies have failed to demonstrate benefits for strict glycaemic control. Metformin is an oral biguanide known to have several metabolic and cellular actions. The present study was undertaken to assess the effect of metformin on peripheral neuropathy outcomes in type 2 diabetes.Methods69 type 2 diabetes participants receiving metformin were recruited and had clinical assessment, peripheral nerve ultrasound, nerve conduction studies and nerve excitability studies performed. 318 participants who were not on metformin were also concurrently recruited and assessed, and 69 were matched to the metformin participants for age, sex, diabetes duration, BMI, HbA1c and use of other diabetes therapies. Medical record data over the previous 20 years were analysed to assess the duration and dose of current or prior metformin therapy in both groups.ResultsMean tibial nerve cross-sectional area (CSA) was improved in the metformin group (metformin 14.1 ± 0.7 mm2, non-metformin 16.2 ± 0.9mm2, p=0.038) and this was accompanied by reduction in neuropathy severity, p=0.021). Nerve excitability studies demonstrated improvements in axonal function in the metformin group and mathematical modelling of excitability data demonstrated that these improvements were mediated by changes in nodal Na+ and K+ conductances.ConclusionMetformin treatment is associated with improved nerve structure and improvements in clinical and neurophysiological measures. Treatment with metformin may be neuroprotective in DPN.