Long-term metformin treatment and risk of peripheral neuropathy in older Veterans

• Type of Material: Article
• Authors: Monica Serra, Emory University; Vijaya Kancherla, Emory University; Anjalii Khakharia, Emory University; Latricia Allen, Emory University; Lawrence Phillips, Emory University; Mary Rhee, Emory University; Peter Wilson, Emory University; Elizabeth Vaughan, Emory University; Camille E Vaughan, Emory University
• Language: English
• Date: 2020-12-01
• Publisher: ELSEVIER IRELAND LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Published by Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.diabres.2020.108486
• Title of Journal or Parent Work: DIABETES RESEARCH AND CLINICAL PRACTICE
• Volume: 170
• Start Page: 108486
• End Page: 108486
• Grant/Funding Information: This study was supported by the Department of Veterans Affairs Birmingham/Atlanta Geriatric Research, Education, and Clinical Center and awards to Dr. Vaughan (IK2 RX000747) and Dr. Phillips (CSP #2008, IK2 CX001907, I01 CX001899, I01 CX001737, and HSR&D IIR 07-138) and the National Institutes of Health awards to Dr. Phillips (R21 DK099716, R18 DK066204, R03 AI133172, U01 DK091958, U01 DK098246, UL1 TR002378). The sponsors had no role in the design, methods, data collection, or analysis of the study and had no role in the preparation of the manuscript.
• Keywords: Metformin; Endocrinology & Metabolism; POPULATION; Aging; Vitamin B12; Life Sciences & Biomedicine; Type 2 diabetes; Veteran; HEALTH; VITAMIN-B12 DEFICIENCY; THERAPY; Science & Technology

Abstract

Aim: Our objective was to assess whether increased duration of metformin therapy is associated with incident peripheral neuropathy (PN) in older Veterans with diabetes. Methods: Using national Veterans Affairs registry data from 2002 to 2015, we examined Veterans (50 + years) with diabetes. Long-term metformin therapy was defined as prescription ≥ 500 mg/day, filled for ≥ 6 consecutive months. Metformin therapy duration was examined both as continuous and categorical measures. Incident PN was defined by medical chart review. We estimated unadjusted and adjusted (variables selected a priori) odds ratios (OR) and 95% confidence intervals (CI) using logistic regression. Results: The study included n = 210,004 individuals (mean ± SD: age: 66.2 ± 8.4 yrs, 96% male) prescribed metformin for 47.0 ± 34.0 months. Nineteen percent developed PN during follow-up. After adjusting for age, body mass index, duration of time receiving health care within the VA, smoking status, alcohol abuse, and vitamin B12 testing and treatment, the number of months of metformin treatment was associated with elevated odds for incident PN (aOR (metformin treatment - continuous) = 1.009 (95% CI = 1.009, 1.010); aOR (metformin treatment – categorical (ref: 6-<18 months): 18-<44.1 months = 1.57 (1.51–1.63), 44.1-<61 months = 2.05 (1.97–2.14), 61 + months = 2.69 (2.58–2.79), all p-values < 0.0001). Conclusion: Our study suggests that Veterans treated for at least 18 months with metformin are approximately 2–3 times more likely to develop PN than those treated at least six, but<18 months. Future studies are needed to determine whether the association we found may be due to a decline in vitamin B12 status following metformin initiation.