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Metformin for ageing

Metformin is a prescription glucose-lowering medicine that has been proposed as a longevity agent for people without diabetes, mainly on the strength of animal studies and an influential 2014 UK cohort in which people with type 2 diabetes starting metformin appeared to outlive matched people without diabetes. Later reanalyses, including a Danish registry and twin study, did not reproduce that survival advantage, and a 2025 review describes an emerging uncertainty about its anti-ageing potential. The TAME trial was proposed to test the idea, but no randomised trial has shown that metformin extends lifespan or healthspan in people. Randomised trials in older adults without diabetes found that it blunted some gains from exercise training, and documented adverse effects include common gastrointestinal effects, lower vitamin B12 with long-term use and rare but serious lactic acidosis. It is a prescription medicine, and decisions about it belong with a prescribing clinician.

  • Longevity
  • Strength

Evidence retrieved up to

What the research shows

An influential 2014 UK cohort reported that people with type 2 diabetes starting metformin lived longer than matched people without diabetes, which fuelled interest in metformin for ageing, but later analyses, including a Danish registry and twin study, did not reproduce that survival advantage and found higher mortality instead.

Low certaintyFurther research is likely to change this.
Take care: see the safety noteNo clear effect

Who this is about

adults with type 2 diabetes starting metformin, compared with matched adults without diabetes

Practical note

Graded low: observational cohorts that disagree with each other; a 2025 review attributes the original signal to time-related and selection biases. The Danish study found 1.32 times the mortality after adjustment in singletons and 1.64 times in discordant twin pairs.

Safety note

Metformin is a prescription medicine; these studies say nothing about its use by people without diabetes.

Sources

No randomised trial has shown that metformin extends lifespan or healthspan in people; the TAME trial was proposed to test it in people without diabetes, and as of a 2025 review it remained a proposal, while key observational findings have generally not been replicated.

Very low certaintyThis is uncertain; treat it as a lead, not a finding.
Take care: see the safety noteUnclear

Who this is about

adults without diabetes

Practical note

Graded very low because there is no direct human trial evidence on lifespan or healthspan. The 2025 review describes the TAME proposal as a phase III randomised placebo-controlled trial in people without type 2 diabetes with a composite endpoint of mortality, major cardiovascular events, incident cancers and cognitive impairment, and reports that metformin did not increase lifespan in mice in the multi-centre Intervention Testing Program.

Safety note

Metformin is a prescription medicine; using it for ageing is outside its approved use.

Sources

In randomised placebo-controlled trials in older adults without diabetes, metformin taken during exercise training reduced gains in lean and thigh muscle mass from resistance training and reduced improvements in insulin sensitivity and aerobic fitness from aerobic training.

Moderate certaintyFurther research may change the size of the effect.
Take care: see the safety noteRisk

Who this is about

older adults without diabetes doing supervised exercise training

Practical note

Graded moderate: two double-blind randomised trials (94 adults aged 65 and older over 14 weeks of resistance training; 53 adults with mean age 62 over 12 weeks of aerobic training) point the same way, downgraded one level for small samples and short duration. The resistance trial found a non-significant trend toward smaller strength gains.

Safety note

Exercise training brought benefits in both trials; the concern is that metformin reduced some of them.

Sources

In adults with raised blood glucose but no diabetes who were randomised to metformin and followed for up to 13 years, long-term metformin use was associated with more low and borderline-low vitamin B12 levels and more anaemia than placebo.

Moderate certaintyFurther research may change the size of the effect.
Take care: see the safety noteRisk

Who this is about

adults with raised blood glucose and overweight, without diabetes at entry, taking metformin long term

Practical note

Graded moderate: randomised comparison for the first 3.2 years, then open-label follow-up, with B12 measured on stored samples in a secondary analysis. Combined low and borderline-low B12 was 20.3 percent versus 15.6 percent at 13 years; each year of metformin use raised the odds of B12 deficiency by about 13 percent.

Vegan note

The US label names people with inadequate vitamin B12 intake as more likely to develop low B12 on metformin, which is relevant to people following an unsupplemented vegan diet.

Safety note

US labelling states that metformin may lower vitamin B12 levels and advises periodic blood checks for people taking it; decisions belong with the prescribing clinician.

Sources

Gastrointestinal effects such as diarrhoea, nausea or vomiting, flatulence, indigestion and abdominal discomfort are among the most common adverse reactions to metformin in clinical trials.

Moderate certaintyFurther research may change the size of the effect.
Take care: see the safety noteRisk

Who this is about

adults taking metformin

Practical note

Graded moderate: placebo-controlled trial data summarised in US prescribing information, downgraded one level for indirectness because the trials enrolled people with type 2 diabetes rather than people taking metformin for ageing.

Safety note

Metformin is a prescription medicine; adverse effects are a matter for the prescribing clinician.

Sources

Metformin carries a boxed warning for lactic acidosis, a rare but serious adverse effect that has been fatal in postmarketing cases.

Low certaintyFurther research is likely to change this.
Caution: see the safety noteRisk

Who this is about

adults taking metformin

Practical note

Graded low for frequency: the evidence is postmarketing case reports summarised in US prescribing information, which describes the risk as rare without giving a rate in the quoted text.

Safety note

Lactic acidosis is a medical emergency. The US label lists risk factors including kidney impairment, age 65 or older, excessive alcohol intake, liver impairment and some procedures and medicines.

Sources