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Metformin, the world’s most prescribed diabetes drug, has long puzzled researchers with its wide-ranging effects beyond glucose control. Now, a new study from Kobe University provides the first clinical evidence that metformin alters blood metal levels in humans, potentially explaining some of its broader benefits.

The research, published in BMJ Open Diabetes Research & Care, analyzed around 200 patients with type 2 diabetes treated at Kobe University Hospital. Half were receiving metformin and half were not. Blood serum samples were tested for levels of copper, iron, zinc, and metal deficiency indicators.

According to study leader Professor Wataru Ogawa, these changes are clinically meaningful: “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.”

Metformin’s ability to bind metals, particularly copper, had been demonstrated in earlier chemical studies, but this is the first time such effects have been shown in humans. The findings may help explain why the drug has beneficial effects on cancer, inflammation, and atherosclerosis, in addition to lowering blood sugar.

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Key highlights
  • First clinical evidence shows metformin changes copper, iron, and zinc levels in humans.
  • Lower copper/iron and higher zinc are linked to improved glucose tolerance and fewer complications.
  • Findings may explain metformin’s broad protective effects beyond blood sugar control.
  • Could guide design of next-generation diabetes drugs.
Source

Otowa-Suematsu, N., et al. (2025). Association of metformin treatment with changes in metal dynamics in individuals with type 2 diabetes. BMJ Open Diabetes Research & Caredoi.org/10.1136/bmjdrc-2025-005255

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Kobe University study shows that metformin lowers copper and iron but raises zinc in blood, offering new clues to its wide-ranging effects.

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