At the latest when the book“Lifespan” (Engl. “The End of Aging”) by Prof. Dr. Dr. Dr. H. H. H. was published. David A. Sinclair was published in 2019, metformin experienced a real hype in the longevity scene. Suddenly, a tried-and-tested diabetes drug was also considered a hot recommendation for healthy people. And so metformin became the most promising candidate for longevity therapies in humans. The longevity community had found its holy grail: A fountain of youth in pill form! And cheap to boot!
A new review by Keys et al. (2025) in Ageing Research Reviews, however, fundamentally shatters these hopes and documents an “emerging uncertainty about the longevity potential of metformin”. Well done!
2014 – The hype surrounding Metformin or how it all began
The foundation was laid by a seemingly sensational study from 2014, in which researchers compared diabetics on metformin with healthy people – and made an astonishing discovery: the diabetics on metformin lived longer than the healthy people. The study had the provocative title: “Can people with type 2 diabetes live longer than those without?”
The result electrified the longevity scene. If sick people were already living longer on metformin than healthy people, what effect would the drug have on healthy people? Demand exploded, doctors prescribed metformin “off-label”, and plans for million-dollar anti-ageing studies gathered pace.
The gold standard fails
But then came the sobering results from the laboratory. The US government’s renowned Intervention Testing Program tests potential anti-ageing drugs on mice under the strictest conditions. 863 mice were given metformin, with a further 863 serving as a control group.
The result was clear:
Metformin did not prolong the life of the mice one bit. Neither in males nor in females, neither in high nor in low doses. A meta-analysis in 2022 confirmed: metformin does not prolong life.
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Clinical trials: one failure after another
Failures also became more frequent in humans:
Cancer: The eagerly awaited MA.32 study tested metformin in 3,682 breast cancer patients. The result after five years: Metformin was ineffective – it neither prolonged survival nor delayed relapses.
Cardiovascular: Several large studies investigated metformin’s cardioprotection in people without diabetes. The CAMERA study (173 participants) found no effect against arteriosclerosis. The GIPS III study (380 participants) showed no improvement after myocardial infarction. The other trials also failed.
Long-term observation: The most important long-term study followed over 3,000 people with pre-diabetes for 20 years. One group received metformin, the other placebo. After two decades, the results were sobering: metformin did not protect against cardiovascular disease, cancer or premature death.
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The Bannister sensation was a mistake
Particularly embarrassing: two independent research groups tried to repeat the sensational Bannister study – and failed spectacularly.
The Danish researchers led by Keys analyzed the data of hundreds of thousands of diabetics and compared them with the general population. Instead of living longer, the metformin patients died more frequently (mortality risk increased by 48-105 percent).
A British study confirmed this over a 20-year observation period: diabetics taking metformin had a 69 percent higher risk of death compared to healthy people.
Why the error survived for so long
How did the metformin myth become so persistent? The Keys analysis uncovers systematic errors in the research:
Side effects are underestimated
What is often overlooked: Metformin is not harmless. Studies show that the drug hinders muscle development in older people – a fatal effect, as muscle wasting is a major risk of ageing. In studies on frailty, many participants stopped taking metformin because they could not tolerate the drug. Nausea, diarrhea and abdominal pain are common side effects.
All that glitters is not gold
The Metformin saga is a good example of how scientific hype can develop and take on a life of its own. What began as a promising breakthrough turned out to be a bubble.
- For diabetics, metformin remains a proven and safe medication for blood sugar control.
- There is no reason for healthy people to take metformin. The risks far outweigh the unproven benefits.
- It’s time for researchers to focus on more promising longevity strategies instead of pouring millions more into futile metformin trials.
The “fountain of youth pill” was an illusion. Longevity cannot be swallowed and continues to work through the tried and tested ways of a healthy life: exercise, a healthy diet, stress reduction and sufficient sleep. Boring? Perhaps. But it works – unlike Metformin.
Sources:
Main source:
- Keys, M.T., Hallas, J., Miller, R.A., Suissa, S., Christensen, K. (2025). Emerging uncertainty on the anti-aging potential of metformin. Ageing Research Reviews, 111, 102817. https://doi.org/10.1016/j.arr.2025.102817
Cited original studies:
- Bannister, C.A., et al. (2014). Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes, Obesity and Metabolism, 16(11), 1165-1173. https://doi.org/10.1111/dom.12354
- Strong, R., et al. (2016). Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Aging Cell, 15(5), 872-884. https://doi.org/10.1111/acel.12496
- Goodwin, P.J., et al. (2022). Effect of Metformin vs Placebo on Invasive Disease-Free Survival in Patients With Breast Cancer: The MA.32 Randomized Clinical Trial. JAMA, 327(20), 1963-1973. https://doi.org/10.1001/jama.2022.6147
- Keys, M.T., et al. (2022). Reassessing the evidence of a survival advantage in type 2 diabetes treated with metformin compared with controls without diabetes: a retrospective cohort study. International Journal of Epidemiology, 51(6), 1886-1898. https://doi.org/10.1093/ije/dyac117
- Stevenson-Hoare, J., Leonenko, G., Escott-Price, V. (2023). Comparison of long-term effects of metformin on longevity between people with type 2 diabetes and matched non-diabetic controls. BMC Public Health, 23, 804. https://doi.org/10.1186/s12889-023-15722-1
- Lee, C.G., et al. (2021). Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Diabetes Care, 44(12), 2775-2782. https://doi.org/10.2337/dc21-1046
- Goldberg, R.B., et al. (2022). Effects of Long-term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome Study. Circulation, 145(22), 1632-1641. https://doi.org/10.1161/CIRCULATIONAHA.121.056756
- Preiss, D., et al. (2014). Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomized controlled trial. The Lancet Diabetes & Endocrinology, 2(2), 116-124. https://doi.org/10.1016/S2213-8587(13)70152-9
- Lexis, C.P.H., et al. (2014). Effect of Metformin on Left Ventricular Function After Acute Myocardial Infarction in Patients Without Diabetes: The GIPS-III Randomized Clinical Trial. JAMA, 311(15), 1526-1535. https://doi.org/10.1001/jama.2014.3315
- Wen, J., et al. (2022). Efficacy of metformin therapy in patients with cancer: a meta-analysis of 22 randomized controlled trials. BMC Medicine, 20, 402. https://doi.org/10.1186/s12916-022-02599-4
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