Metformin Linked to Measurable Shifts in Essential Metal Levels, new Study Reveals
Kobe, Japan – A new study published in BMJ open diabetes Research & Care has revealed that the widely-prescribed diabetes drug metformin is associated with significant alterations in the levels of copper, iron, and zinc in patients with type 2 diabetes.Researchers at Kobe University found that metformin use correlated with reduced copper and iron levels, and increased zinc levels, suggesting the drug’s metal-binding properties have tangible effects within the human body.
The research, led by Dr. Nobuhiro Ogawa, analyzed data from individuals with type 2 diabetes and found those taking metformin exhibited lower copper levels (3 µmol/L) alongside indicators of latent iron deficiency. conversely, zinc levels were higher in metformin users (13.3 vs 12.5 µmol/L). The study also confirmed previously reported findings of lower Vitamin B12 and elevated homocysteine levels in patients on metformin.
These associations persisted even after researchers accounted for factors like age, sex, body mass index, kidney function, and other medications. Multiple regression analysis definitively identified metformin use as an independent predictor of these metal level changes. Subgroup analyses further reinforced the consistency of the findings across different demographics and medication regimens.
“It is indeed significant that we could show this in humans,” stated Dr. Ogawa. “Moreover,as decreases in copper and iron concentrations and an increase in zinc concentration are all considered to be associated with improved glucose tolerance and prevention of complications,these changes may indeed be related to metformin’s action.”
The findings suggest metformin’s known ability to bind metals isn’t merely a laboratory phenomenon, but actively influences metabolic processes. Researchers hypothesize these metal shifts may contribute to the drug’s glucose-lowering effects and its protective benefits against diabetes complications, aligning with preclinical studies demonstrating that reduced copper availability can impact mitochondrial function, inflammation, and even tumor growth.
The study also opens avenues for investigating the mechanisms of other antidiabetic drugs. Researchers are currently comparing metformin to imeglimin, a recently approved metformin derivative in Japan that lacks the same metal-binding properties.
“Imeglimin is thought to have a different method of action and we are already conducting studies to compare the effects the two drugs have,” Dr. Ogawa added. He emphasized the need for further clinical trials and animal experiments to establish a definitive causal link, potentially paving the way for novel diabetes treatments focused on optimizing metal concentrations within the body.
Reference: Otowa-Suematsu N, Sakaguchi K, Yamada T, et al.Association of metformin treatment with changes in metal dynamics in individuals with type 2 diabetes. BMJ Open Diabetes Res Care. 2025.doi: https://doi.org/10.1136/bmjdrc-2025-005255
