Diabetes Drug Metformin Shows Promise as an Anti-Aging Treatment, Review Finds

Metformin, a widely prescribed, safe and inexpensive first-line treatment for type 2 diabetes, lowers blood sugar and appears to trick cells into sensing an energy shortage similar to fasting, activating a cellular energy sensor called AMPK that triggers waste cleanup and repair. A new review published in the journal Aging compiled decades of cellular, animal and human research into a single picture of how metformin might also act as a geroprotective agent, targeting biological root causes of aging.

The effects appear across species. Male monkeys treated with metformin for 40 months showed tissues that were biologically younger, with their brains alone reversing by nearly 6 years, equivalent to about 18 years in human terms. In humans, observational data found people taking metformin had biological ages up to 3.43 years younger, and people with diabetes who took the drug lived as much as 15% longer than peers without diabetes.

The researchers caution that the evidence is mixed: a widely publicized study linking metformin to a survival advantage in humans has recently faced criticism after other researchers could not reproduce its results, and most human studies involve people with diabetes, making it hard to separate any anti-aging effect from the drug's effect on the underlying disease. In cell studies, metformin triggers autophagy, the cell's cleanup system, and stabilizes an enzyme called TET2 that slows abnormal age-related changes to DNA, while also boosting beneficial, mucus-protecting gut bacteria linked to lower age-related inflammation.

In the microscopic worm C. elegans, metformin extended lifespan by 36% to 40%; in mice, it increased average lifespan by 5.8% to 20.1% across different models and delayed the onset of certain tumors. The researchers say the biggest gap in the field is the lack of large, rigorous trials in healthy adults without diabetes, and are hopeful that the ongoing Targeting Aging with Metformin (TAME) trial will help confirm whether the drug can delay multiple age-related diseases in humans.