The effect of metformin on peripheral nerve morphology in type 2 diabetes: a cross-sectional observational study

Diabetic peripheral neuropathy (DPN) affects around 50% of the 500 million people with type 2 diabetes worldwide and is considered disabling and irreversible. The present study was undertaken to assess the effect of metformin on peripheral neuropathy outcomes in type 2 diabetes. 69 type 2 diabetes participants receiving metformin were recruited and underwent clinical assessment, peripheral nerve ultrasound, nerve conduction studies and axonal excitability studies. 318 participants who were not on metformin were also concurrently screened, and 69 were selected as disease controls and 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 for previous metformin use. Mean tibial nerve cross-sectional area (CSA) was lower in the metformin group (metformin 14.1 ∓ 0.7 mm2, non-metformin 16.2 ∓ 0.9mm2, p=0.038), accompanied by reduction in neuropathy symptom severity (p=0.021). Axonal excitability studies demonstrated superior axonal function in the metformin group and mathematical modelling demonstrated that these improvements were mediated by changes in nodal Na⁺ and K⁺ conductances. Metformin treatment is associated with superior nerve structure, clinical and neurophysiological measures. Treatment with metformin may be neuroprotective in DPN.