For decades, people have dreamed of medicines that could slow ageing and help us live not only longer but healthier lives. Among the many candidates, one drug stands out for its surprising potential: metformin. Originally developed in the 1940s and introduced for diabetes in the 1950s, this inexpensive pill has been prescribed to millions of people with type II diabetes. Over the years, researchers noticed intriguing patterns suggesting it might do more than just control blood sugar. Could metformin be the world’s first widely available anti-ageing drug?
The excitement was fueled by laboratory experiments, small-scale studies, and even epidemiological findings suggesting people with diabetes taking metformin might outlive those without the disease. Yet as more rigorous studies emerged, doubts began to surface. The story of metformin and ageing has become one of promise, contradiction, and scientific caution.
Early laboratory promise
In animal models, metformin showed striking effects. Rodents treated with the drug sometimes lived longer, displayed fewer signs of inflammation, and even exhibited cellular changes similar to those seen under caloric restriction, long known to extend lifespan in lab organisms. These results gave scientists hope that the drug could influence core biological processes tied to ageing, including mitochondrial function and oxidative stress.
Such findings encouraged optimism. If a drug as familiar and safe as metformin could extend lifespan in animals, perhaps it could one day be repurposed for healthy people. The notion was simple yet revolutionary: instead of waiting to treat age-related diseases, we could try to slow the ageing process itself.
Success in diabetes treatment
Metformin’s reputation was already strong because of its role as the first-line therapy for type II diabetes. Large trials like the UK Prospective Diabetes Study showed it reduced diabetes-related deaths and complications more effectively than many other treatments. Cardiovascular protection appeared especially promising, raising the possibility that the drug’s benefits might extend beyond blood sugar control.
By the early 2000s, observational studies added further weight. Researchers reported that metformin users seemed less likely to develop cancer, dementia, and other conditions linked with ageing. Some even claimed that people with diabetes on metformin survived longer than peers without diabetes, an astonishing and counterintuitive suggestion that fueled headlines worldwide.
Rise of uncertainty
As scientists dug deeper, cracks in the evidence began to show. Replications of key studies often failed to confirm the early optimism. The largest and most rigorous animal trials, such as the National Institute on Aging’s Intervention Testing Program, did not find significant lifespan extension from metformin. Observational studies that once suggested dramatic cancer protection were later shown to suffer from biases in design, such as immortal time bias and flawed control groups.
Even clinical trials in humans produced mixed outcomes. While small studies hinted at benefits in frailty, cognition, and osteoarthritis, larger randomized trials failed to show consistent effects against cancer, cardiovascular disease, or overall survival in people without diabetes.
COVID-19 and new directions
During the COVID-19 pandemic, metformin entered another spotlight. Some trials suggested it might reduce the severity of infection or lower the risk of developing long COVID. Others found no effect at all. These mixed findings mirrored the broader uncertainty that now surrounds the drug’s potential role in ageing.
Interestingly, preliminary results in elderly monkeys hinted that metformin could slow biological markers of ageing and improve cognitive performance. However, lifespan data in longer-lived animals remain absent, leaving the translation to humans unresolved.
Where science stands now
Taken together, the evidence suggests metformin is not a miracle drug for ageing. It remains an effective, safe, and affordable therapy for type II diabetes, but its benefits beyond that condition are far from certain. While some small and focused trials continue, the weight of current data shows little consistent protection against cancer, frailty, or cardiovascular disease in healthy or prediabetic individuals.
This does not mean research should stop. Metformin still offers a valuable case study in how ageing science should proceed: cautiously, transparently, and with an eye toward the complex biases that can shape our interpretations. Whether or not the drug ultimately earns a place as an anti-ageing therapy, its story has already reshaped how scientists design and assess trials aimed at the biology of ageing.
The bigger lesson
Metformin has taken the scientific community on a remarkable journey. From early excitement to sobering reassessment, it demonstrates the importance of rigorous testing before drawing bold conclusions. The questions raised by metformin are not just about one drug. They highlight the broader challenge of finding interventions that can truly modify the ageing process.
As large-scale trials continue into the late 2020s, the final word on metformin’s role in longevity may still be years away. Until then, its story is a reminder that in science, especially in the field of ageing, hope and evidence must always be balanced.
The study is published in the journal Ageing Research Reviews. It was led by Matthew Thomas Keys from the University of Southern Denmark.
