Huang Kuang-Hua, Huang Shiang-Wen, Yang Yih, Gau Shuo-Yan, Tsai Tung-Han, Chang Ya-Lan, Lee Chien-Ying
Department of Health Services Administration, China Medical University, Taichung, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Sci Rep. 2025 Apr 8;15(1):12040. doi: 10.1038/s41598-025-96445-1.
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.
本研究调查了2型糖尿病（T2DM）患者使用二甲双胍与糖尿病周围神经病变（DPN）风险之间的相关性及其剂量依赖关系。该研究纳入了2002年至2013年新诊断的T2DM患者。根据二甲双胍治疗情况将患者分为两组，并在2年和5年随访时评估DPN风险。在对各种因素进行校正后，采用两个逻辑模型，即二甲双胍累积限定日剂量（cDDD）和二甲双胍治疗强度（限定日剂量[DDD]/月），评估二甲双胍与DPN风险的关联。结果显示，二甲双胍cDDD＜300、300 - 500和＞500的患者在两次随访时DPN风险均较高。2年时DPN的比值比（OR）和置信区间（CI）分别为1.74（1.69 - 1.79）、2.05（1.81 - 2.32）和2.36（1.34 - 4.16），5年时分别为1.63（1.60 - 1.65）、1.82（1.69 - 1.96）和2.17（1.56 - 3.03）。同样，每月DDD＜10、10 - 25和＞25的患者在两次随访时DPN风险也较高。T2DM患者使用二甲双胍与DPN风险相关，且存在剂量依赖关系。较高的二甲双胍cDDD或治疗强度会增加DPN风险。然而，缺乏维生素B12数据限制了对潜在机制的理解。需要设计良好的大规模研究来评估二甲双胍治疗对T2DM患者DPN的潜在风险。
