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Association of metformin treatment with changes in metal dynamics in individuals with type 2 diabetes

Otowa-Suematsu N, Sakaguchi K, Yamada T, Nishisaka M, Morita Y, Fukumitsu H, Katsura Y, Okada Y et al.

BMJ open diabetes research & care, 2025

189 participants

Abstract

INTRODUCTION: The metal-chelating activity of metformin, which has long been known but of unclear clinical relevance, has recently been implicated in the pleiotropic effects, including antitumorigenic and anti-inflammatory actions, of the drug. However, whether metformin actually influences metal dynamics in humans has remained unknown. We here investigate whether metformin influences serum metal levels in individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS: In this cross-sectional study, individuals with type 2 diabetes treated or not treated with metformin for at least 6 months were recruited. The primary outcome was the difference in serum copper concentration between metformin users and non-users. Secondary outcomes included differences in serum levels of iron, zinc, and vitamin B12 as well as in copper-related and iron-related parameters between the two groups.

RESULTS: A total of 189 individuals (93 metformin users and 96 non-users) were analyzed. Metformin users showed significantly lower serum copper (16.0 vs 17.8 µmol/L, p<0.001) and iron levels (16.3 vs 17.3 µmol/L, p=0.02) and higher zinc levels (13.3 vs 12.5 µmol/L, p=0.01) compared with non-users. Copper-related and iron-related parameters for metformin users were consistent with latent deficiencies of these metals. Serum homocysteine levels (12.2 vs 11.2 µmol/L, p=0.03) were significantly higher, whereas vitamin B12 levels (338.7 vs 412.8 pmol/L, p<0.001) were significantly lower, in metformin users.…

How strong is the evidence?

Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 189 participants or records.

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