Kobe University researchers discovered that metformin alters blood metal levels, lowering copper and iron while raising zinc. This metal effect may explain its broad health benefits and guide future diabetes drug development.
For more than 60 years, metformin has been the world’s most prescribed diabetes drug, best known for lowering blood sugar. But doctors have long noticed that its benefits go far beyond diabetes — from lowering inflammation to reducing cancer risk. What’s puzzled scientists is why.
Now, researchers at Kobe University may have found a major clue. Their clinical study, published in BMJ Open Diabetes Research & Care, shows that metformin changes levels of key metals in the blood.
The team studied about 200 diabetes patients, half of whom were on metformin. They found that patients taking the drug had significantly lower copper and iron levels, but higher zinc levels. These shifts in metal balance are thought to improve glucose tolerance and help prevent complications — offering the first direct evidence in humans that metformin’s “metal effect” may be behind its surprising range of health benefits.
Lead researcher Dr. Wataru Ogawa explains that while chemical studies hinted at metformin’s ability to bind metals like copper, this is the first proof in patients. The findings could help scientists design next-generation diabetes treatments that mimic or improve upon metformin’s action.
Japan has already approved imeglimin, a metformin-derived drug believed to act differently because it does not bind metals the same way. Researchers are now comparing the two drugs to better understand how they work.
Dr. Ogawa believes this line of research could lead to new drugs targeting diabetes and its complications by carefully adjusting metal concentrations in the body.
This work was supported by the Japan Society for the Promotion of Science and the Manpei Suzuki Diabetes Foundation, with collaboration from Kagayaki Diabetes and Endocrinology Clinic Sannomiya.