Dose dependent relationship of metformin use and diabetic peripheral neuropathy risk in patients with type 2 diabetes mellitus

This study investigated the correlation between metformin use and diabetic peripheral neuropathy (DPN) risk in patients with type 2 diabetes mellitus (T2DM) and its dose-dependent relationship. The study included new-onset T2DM patients from 2002 to 2013. Patients were divided into two groups based on metformin treatment, and DPN risk was assessed at 2- and 5-year follow-ups. After adjusting for various factors, two logistic models, metformin cumulative defined daily dose (cDDD) and metformin treatment intensity (defined daily dose [DDD]/month), evaluated the metformin-DPN risk association. Results showed that patients with metformin cDDD < 300, 300–500, and > 500 had higher DPN risk at both follow-ups. Odds ratios (ORs) and confidence intervals (CIs) for DPN were 1.74 (1.69–1.79), 2.05 (1.81–2.32), and 2.36 (1.34–4.16) at 2 years and 1.63 (1.60–1.65), 1.82 (1.69–1.96), and 2.17 (1.56–3.03) at 5 years. Similarly, patients with < 10, 10–25, and > 25 DDD/month had higher DPN risk at both follow-ups. Metformin use correlated with DPN risk in T2DM patients, with a dose-dependent relationship. Higher metformin cDDD or treatment intensity increased DPN risk. However, the absence of vitamin B12 data limits the understanding of the underlying mechanisms. Well-designed, large-scale studies are required to evaluate the potential risks of metformin therapy for DPN in patients with T2DM.