NEW YORK, July 10 — The most ambitious attempt yet to prove that a cheap generic drug can slow human ageing is now in the field, enrolling patients across 14 US medical centres. The TAME trial — Targeting Aging with Metformin — aims to answer a question that has hovered over geroscience for a decade: can a pill that costs pennies a day delay the onset of multiple age-related diseases at once?
The trial was conceived by Dr. Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York City. It received FDA approval in 2016 as a study of ageing itself, not of any single disease — a regulatory milestone that acknowledged the possibility of treating the biological process of growing old as a legitimate target for clinical investigation.
Metformin was first approved in the US in 1995 as a treatment for type 2 diabetes. It is now generic, widely available, and taken by millions of people daily. The TAME protocol calls for 3,000 adults aged 65 to 79, none of whom have diabetes, to take 1,500 mg of the drug daily for six years.
The primary endpoint is a composite measure: time to a new diagnosis of one of four age-related conditions — cardiovascular disease, cancer, dementia — or death. The trial is funded by the American Federation for Aging Research, founded in 1981, and the National Institutes of Health, with a budget of approximately $75 million.
As of 2024, enrollment was ongoing. Results are expected around 2028.
Under the hood: what metformin does
The technical reality is that metformin appears to mimic some of the cellular effects of caloric restriction, the most robustly validated intervention for extending lifespan in laboratory animals. It activates AMPK, or AMP-activated protein kinase, a master regulator of energy metabolism, and inhibits mTOR, a signalling pathway that promotes cell growth and is implicated in ageing. Observational data have been striking.
A 2014 UK study of 180,000 people with type 2 diabetes found that metformin users had a 15% lower mortality rate than non-diabetic controls — meaning the drug seemed to confer a survival advantage even over people without the disease. The detail that matters here is that these were people with diabetes, not healthy volunteers, making the finding suggestive but far from conclusive.
Critics note that observational data cannot prove causation. People who take metformin may differ in other ways — diet, exercise, healthcare access — that explain the mortality benefit. The TAME trial is designed to settle that question with a randomised, placebo-controlled design.
The regulatory milestone
The FDA’s decision in 2016 to approve TAME as a study of ageing itself, rather than of a specific disease, was the detail that mattered most for the field. It signalled that the agency considered ageing a legitimate target for drug development, opening the door for future therapies designed to slow the biological clock. The trial is being conducted at 14 US medical centres, including the Mayo Clinic, Harvard, and the University of Texas.
Each site is enrolling participants aged 65 to 79 who are free of the major age-related diseases at baseline.
What to watch next
The TAME trial is the first large-scale human test of the geroscience hypothesis — the idea that targeting the fundamental mechanisms of ageing can prevent multiple chronic diseases simultaneously. If it succeeds, the implications for public health would be enormous. If it fails, it will still provide the most rigorous data yet on the limits of repurposing existing drugs for longevity.
The results, expected around 2028, will take years to analyse and interpret. The field will be watching. Consult your doctor for medical advice.
