Does metformin slow aging without diabetes?

We don't know yet whether metformin slows aging in people without diabetes. The longest trial found no drop in deaths, and a recent trial in frail older adults found no gain in walking speed.

Who it's for

No group without diabetes has a proven benefit; people with diabetes use it for blood sugar.

What to expect

No clear benefit for lifespan or function in people without diabetes.

Watch out for

Side effects were common, and a rare but serious blood acid buildup (lactic acidosis) is possible.

What the studies show

• A trial of 3,234 adults at high risk for diabetes, followed a median of 21 years, found metformin did not change deaths from any cause, cancer or heart disease compared with a dummy pill (placeboplacebo A dummy treatment that looks like the real one, so people can't tell which they got.)5Randomized trial · 2021 · 3,234 peopleEffect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.Cancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.Diabetes Care. Metformin did cut new diabetes cases by 31% compared with placebo8Randomized trial · 2002 · 9 peopleReduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.N Engl J Med. This is the strongest evidence, but few people died, so small effects can't be ruled out.
• A trial of 72 frail older adults (average age about 80) gave 1,500 mg of metformin a day for 4 months. Walking speed was the same as with placebo. Hospital stays were more common (12 of 35 people versus 3 of 36), and the authors called it poorly tolerated10Randomized trial · 2025 · 268 peopleMetformin and physical performance in older people with probable sarcopenia and physical prefrailty or frailty in England (MET-PREVENT): a double-blind, randomised, placebo-controlled trial.Metformin did not improve 4-m walk speed and was poorly tolerated in this population.Lancet Healthy Longev.
• A trial of 53 healthy older adults found metformin weakened the gains from 12 weeks of aerobic exercise. Fitness and insulin response improved less, and muscle energy-making improved less2Randomized trial · 2019 · 27 peopleMetformin inhibits mitochondrial adaptations to aerobic exercise training in older adults.The influence of metformin on AET-induced improvements in physiological function was highly variable and associated with the effect of metformin on the mitochondria. These data suggest that prior to prescribing metformin to slow aging, additional studies are needed to understand the mechanisms that elicit positive and…Aging Cell.
• A small trial of 20 healthy older adults found metformin before 5 days of bed rest was linked to less muscle scarring and fewer markers of aging cells. These were lab markers, not strength or lifespan3Randomized trial · 2023 · 20 peopleDisuse-induced muscle fibrosis, cellular senescence, and senescence-associated secretory phenotype in older adults are alleviated during re-ambulation with metformin pre-treatment.Moreover, metformin treatment reduced primary muscle resident fibro-adipogenic progenitors (FAPs) senescent markers and promoted a shift in fibroblast fate to be less myofibroblast-like. Together, these results suggest that metformin pre-treatment improved ECM remodeling after disuse in older adults by possibly…Aging Cell.
• A review pooling 53 studies linked metformin to fewer deaths. Among people with diabetes, those taking metformin had a 28% lower relative riskrelative risk How much more or less likely something is in one group than another, as a ratio. A big relative change can still be a small change for any one person. of death than those on other drugs4Meta-analysis · 2017Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis.Differences in baseline characteristics were observed which had the potential to bias findings, although statistical adjustments were made. The apparent reductions in all-cause mortality and diseases of ageing associated with metformin use suggest that metformin could be extending life and healthspans by acting as a…Ageing Res Rev. These studies were observationalobservational Studies that watch what happens to people rather than assigning a treatment. They can show links, not cause and effect., so differences between the groups could explain the result. Figures like these compare groups, so one person's gain depends on their starting risk.
• In a small trial of people with heart failure but no diabetes, metformin lowered blood markers of inflammation. The trial did not measure aging outcomes7Randomized trial · 2016Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status.We conclude that anti-inflammatory properties of metformin are exerted irrespective of diabetes mellitus status. This may accelerate investigation of drug utility in nondiabetic cardiovascular disease groups.Circ Res.

Key studies

Safety

Metformin carries a boxed warning for lactic acidosis, which has caused deaths. Early signs are vague: tiredness, muscle aches, trouble breathing, sleepiness and belly pain11Guideline · 2024Metformin: FDA drug label (prescribing information)Contraindications: Metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) . Hypersensitivity to metformin. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Severe renal impairment (eGFR below 30 mL/min/…US Food and Drug Administration. It is not for people with severe kidney impairment, metabolic acidosis or an allergy to it11Guideline · 2024Metformin: FDA drug label (prescribing information)Contraindications: Metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) . Hypersensitivity to metformin. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Severe renal impairment (eGFR below 30 mL/min/…US Food and Drug Administration. In the frailty trial, every metformin user had a side effect, versus 92% on placebo10Randomized trial · 2025 · 268 peopleMetformin and physical performance in older people with probable sarcopenia and physical prefrailty or frailty in England (MET-PREVENT): a double-blind, randomised, placebo-controlled trial.Metformin did not improve 4-m walk speed and was poorly tolerated in this population.Lancet Healthy Longev. Metformin is approved for type 2 diabetes. It isn't FDA approved to slow aging, and a prescriber sets any dose.

What we don't know

• Whether metformin changes lifespan or age-related disease in healthy people. The TAME trial was designed to test this1Meta-analysis · 2022Metformin: Is it a drug for all reasons and diseases?We conclude that the primary clinical benefits of metformin result from its insulin-sensitizing and antihyperglycaemic effects that secondarily contribute to a reduced risk of a number of diseases and thereby enhancing healthspan. However, benefits like improving vascular endothelial function that are independent of…Metabolism,9Review · 2016Metformin as a Tool to Target Aging.Aging has been targeted by genetic and dietary manipulation and by drugs in order to increase lifespan and health span in numerous models. Metformin, which has demonstrated protective effects against several age-related diseases in humans, will be tested in the TAME (Targeting Aging with Metformin) trial, as the…Cell Metab.
• Whether any benefit appears in healthy, younger or middle-aged adults, since the trials were short or enrolled people at risk of diabetes or frail older people.