Categories: Longevity
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Daniela Wiessner

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Studie 2025 Metformin

This article was updated on 02.02.2026.

At the latest when the book“Lifespan” (Engl. “The End of Aging”) by Prof. 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 the Ageing Research Reviews and the so-called MET-PREVENT study by Witham MD, McDonald C, Wilson N, et al. fundamentally shake these hopes. They document 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 the males nor in the 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.
  • 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.

  • MET-PREVENT study:

    The MET-PREVENT study – published in March 2025 – was a four-month, double-blind, placebo-controlled RCT designed to assess whether metformin can improve physical performance in frail older adults. Participants had a mean age of 80.4 years and met the inclusion criteria for probable sarcopenia and physical prefrailty or frailty (e.g. maximum handgrip strength < 16 kg in women and < 27 kg in men, 4-meter walking speed of < 0.8 m/s), so this group was at high risk of adverse events such as falls and fractures.

    Participants were randomized to receive either immediate-release metformin at a usual dose of 500 mg three times daily (n = 36) or matching placebo (n = 36). Randomization was based on gender and baseline walking speed (≤0.6 m/s vs. >0.6 m/s). The primary endpoint was the change in 4-meter walking speed from baseline, adjusted for baseline values, as this test is considered a measure of frailty according to the European Working Group on Sarcopenia in Older People (EWGSOP) guidelines.

    After four months, the results in the intent-to-treat population were strikingly clear: metformin showed no statistically significant benefit in improving the primary endpoint. Compared to a mean 4-meter walking speed of only 0.59 ± 0.17 m/s in the metformin group, the post-treatment mean was virtually unchanged (0.57 ± 0.19 m/s), and the results in the placebo group were essentially identical to those in the metformin group (from a baseline value of 0.60 ± 0.26 m/s to a post-treatment value of 0.58 ± 0.24 m/s). This corresponded to a non-significant adjusted treatment effect of 0.001 m/s (95% CI: -0.06-0.06; P=0.96).

    Even in the per-protocol analysis (restricted to participants with at least 80% adherence), the results were consistent with the primary analysis. Subgroup analyses by age, gender, baseline walking speed and insulin resistance also showed no significant differential effects, and secondary endpoints using other sarcopenia measures showed a similar picture to the 4-meter walk test.

    Overall, the results showed no significant differences between the groups in terms of strength, mobility, muscle mass or quality of life.

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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:

  • Biased comparisons: Many studies compared metformin with other diabetes drugs, which themselves increase the risk of death. Metformin looked better than it actually was.

  • Methodological tricks: Researchers often excluded patients from the analysis as soon as they needed additional medication – precisely those who were worse off.

  • Publication bias: Positive results were published more frequently than negative ones, which distorted the overall picture.

Side effects are underestimated

What is also often overlooked: Metformin is not harmless. Studies show that the drug impairs muscle development in older people – a fatal effect, as muscle atrophy or sarcopenia is a major risk of ageing.

Overview of potential disadvantages:

  • Muscle-building interference: Several studies show that metformin can impair the positive adaptations caused by strength training
  • Mitochondrial function: Could inhibit mitochondrial biogenesis
  • Lactate levels: Increased lactate could be problematic during intensive training
  • Vitamin deficiency: metformin can impair B12 absorption

The same applies to longevity research: 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.

Conclusion of the author: For healthy people without diabetes, there is currently no convincing evidence to take metformin to prolong life. The potential risks (especially for active people) could outweigh the unclear benefits.

Better: focus on proven interventions such as exercise, nutrition and sleep.

This shows us once again that when it comes to longevity, it is important not to jump on every bandwagon immediately, as not every “hype” in the longevity scene stands up to scientific scrutiny. This underlines all the more the importance of evidence-based approaches and further research.

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:

  • Witham MD, McDonald C, Wilson N, Rennie KJ, Bardgett M, Bradley P, Clegg AP, Connolly S, Hancock H, Hiu S, Nicholson K, Robertson L, Simms L, Steel AJ, Steves CJ, Storey B, Wason J, von Zglinicki T, Sayer AA. Metformin and physical performance in older people with probable sarcopenia and physical prefrailty or frailty in England (MET-PREVENT): a double-blind, randomized, placebo-controlled trial. Lancet Healthy Longev. 2025 Mar;6(3):100695. doi: 10.1016/j.lanhl.2025.100695. Epub 2025 Mar 24. PMID: 40147475.

  • 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

Pictures:

  • istockphoto.com: Woman when she was young and old | credits @ Yuri_Arcurs
  • Getty Images for Canvas: Metformin formula | credits @ zerbor

🩺 Medically examined on 28.9.2025 and 02.20.2026

This article has been professionally reviewed by Dr. med. Alexander Hammouda, specialist in general medicine with a focus on integrative medicine, functional medicine longevity and prevention. Dr. Hammouda combines in his Munich private practice conventional medical know-how with modern longevity concepts.

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