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Longevity supplements › Metformin and Aging

Does metformin slow aging in people without diabetes?

Updated Nov 14, 2026 · 60 papers read from PubMed abstracts · 26 on topic

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Short answer

Not shown in people without diabetes.

Two trials in older or at-risk adults found metformin did not improve walking speed or distance. Fewer deaths were seen only in people with diabetes, mostly in population studies.

Confidence

Low

What “low” means

This page says what the research shows. It does not say whether you should take metformin.

Where the evidence stands

Each dot is one on-topic paper. Steps near the top answer the question more directly. Select a dot to see the study.

↑ Stronger evidence

  1. Trials in people: aging and age-related disease

    Trials that measured aging, frailty and death in people without diabetes directly.

    1

    1 benefit

  2. Trials in people: other measures

    Trials that measured other health or performance measures.

    3

    2 no difference, 1 harm

  3. Trials in people: lab tests or safety

    Trials that measured lab tests, side effects or safety.

    6

    2 benefit, 2 mixed, 2 no difference

  4. Population studies

    Studies that followed or surveyed groups of people. They show links, not causes.

    8

    6 benefit, 2 no difference

  5. Blood levels and genes

    Studies that link blood levels or genes to health.

    0

    None among the papers we read.

  6. Animals

    Studies in mice, rats, worms or flies.

    3

    2 benefit, 1 harm

↓ Weaker evidence

  • Points to benefit
  • Mixed
  • No difference
  • No direction
  • Points to harm

Not on the ladder: 3 reviews of many studies (shown below), 2 opinion or narrative papers. Counts are papers, not people. Some studies appear in more than one paper.

See every study

What we found

  • In 72 people aged 65 and over with weak muscles and slow walking, 4 months of metformin did not change walking speed: 0·57 m/s versus 0·58 m/s on placebo. Witham 2025
  • Twenty years after a trial in 1830 people at high risk of diabetes, the metformin and placebo groups walked similar distances in 6 minutes: 364 m and 360 m. Munshi 2024
  • A review of 53 studies found people with diabetes on metformin died slightly less often than people without diabetes (hazard ratio 0.93). These studies show links, not causes. Campbell 2017
  • Animal results split: metformin at 0.1% of food from middle age lengthened life in male mice, but metformin given late in life shortened life in worms. Martin-Montalvo 2013, Espada 2020

What the research says

Trials of walking and frailty found no benefit

MET-PREVENT gave 72 people aged 65 and over with weak muscles and prefrailty or frailty 500 mg of metformin or placebo three times a day for 4 months. Walking speed ended the same (0·57 vs 0·58 m/s). More metformin users went to hospital: 12 (34%) versus three (8%).

The Diabetes Prevention Program gave adults at high risk of diabetes metformin, a lifestyle program or placebo for 3 years. Twenty years later, 1830 were tested: 6-minute walk distances were 364, 362 and 360 m (p = 0.8), meaning no real difference.

Studies: Witham 2025, Munshi 2024

Fewer deaths seen only in people with diabetes

In the UKPDS 34 trial, 753 overweight adults with new type 2 diabetes got metformin or mostly diet for a median 10.7 years. The metformin group had 36% lower risk of death from any cause. In a side trial, adding metformin to sulphonylurea went with 96% higher diabetes-related death.

Population studies of people with diabetes, including those with kidney disease, liver cancer or esophageal cancer, link metformin use to fewer deaths. A review of 53 studies found a hazard ratio of 0.72 versus other diabetes drugs, meaning a lower death rate. These studies show links, not causes.

Studies: Unknown 1998, Campbell 2017, Charytan 2019, Lambourg 2025, Li 2022, Wang 2023

Small marker trials in older adults pointed both ways

Several small trials measured body markers, not aging itself. In 20 healthy older adults on bed rest, metformin meant less muscle shrinkage and lower cell-aging markers. In people with HIV and normal blood sugar, blood-cell age estimates fell by 3.53 and 1.84 years on two DNA-based clocks.

Other trials found no change or a cost. Metformin did not change a blood marker of biological age in men aged 29 to 45, or aging signs in 105 placentas. In older adults, it blunted fitness gains from aerobic exercise and muscle growth from strength training.

Studies: Petrocelli 2023, Corley 2024, Vinicki 2025, Hattersley 2025, Konopka 2019, Kulkarni 2020

Brain and memory results disagree

In UK Biobank, among people with type 2 diabetes, metformin treatment was not linked to better brain scans or thinking scores. In three Alzheimer's research cohorts, the largest with 28 044 people, metformin use was linked to slower decline on a dementia rating score.

A smaller study found metformin changed gut bacteria, but a bacteria ratio was linked to memory only in men, not in all users. These are mostly population studies, so they show links, not causes.

Studies: Antal 2022, Wang 2026, Rosell-Díaz 2024

Animals: longer life in mice, shorter in old worms

Male mice given 0.1% metformin in food from middle age lived longer and stayed healthier; a 1% dose was toxic. In worms, metformin started late in life shortened lifespan, and it drained cell energy in old worms and aged human cells grown in dishes.

In mice aged early with the drug doxorubicin, metformin reversed some markers of aging cells. None of these animal results test people.

Studies: Martin-Montalvo 2013, Espada 2020, Sun 2022

What reviews of many studies found

Reviews pool or sum up earlier studies. They are not on the ladder, because they repeat studies already counted there.

  • Pooled review (meta-analysis) · Campbell 2017

    Included 53 of 260 studies read in full, comparing metformin users with diabetes to others. Users had lower death rates than people without diabetes (HR 0.93) and than diabetics on other drugs (HR 0.72). Group differences could bias this.

  • Pooled review (meta-analysis) · Maruthur 2016

    Pooled 179 trials and 25 observational studies of diabetes drugs in adults with type 2 diabetes. Heart-related death was lower with metformin than with sulfonylureas. Evidence on death from any cause was insufficient or of low strength.

  • Pooled review (meta-analysis) · Li 2022

    Pooled studies of people with diabetes; the abstract does not give the count. Metformin use was linked to lower liver cancer risk (OR/RR = 0.59) and fewer deaths among people with liver cancer (HR = 0.74). Study results varied widely.

How the research grew

The papers we read span 1998 to 2026. 8 of the 26 on-topic papers came out in 2024 to 2026. The earliest trial in people here is from 1998.

Trials in people
Population studies
Animal and cell
Reviews
Opinion
1995–99
2000–04
2005–09
2010–14
2015–19
2020–24
2025–26
  1. 1995–99
    Trials in people
  2. 2010–14
    Animal and cell
  3. 2015–19
    Trials in peoplePopulation studiesReviewsOpinion
  4. 2020–24
    Trials in peoplePopulation studiesAnimal and cellReviewsOpinion
  5. 2025–26
    Trials in peoplePopulation studies

Each dot is one on-topic paper, colored by what it found. Rings mark key papers:

  1. 1998. UKPDS 34: metformin trial cut deaths in diabetes. Unknown 1998
  2. 2013. Metformin lengthened lifespan in middle-aged male mice. Martin-Montalvo 2013
  3. 2017. Review links metformin users to fewer deaths. Campbell 2017
  4. 2020. Late-life metformin shortened lifespan in worms. Espada 2020
  5. 2025. Frailty trial: no gain in walking speed. Witham 2025

Who was studied

Who took part, and how many. The largest trial here had 1,830 people; the largest population study had 188,983.

  1. Trials in people
  2. 1,830 people · Munshi 2024
    Adults at high risk of type 2 diabetes (not yet diabetic at start), tested for walking 20 years later
  3. 753 people · Unknown 1998
    Overweight adults with newly found type 2 diabetes, average age 53
  4. 105 people · Hattersley 2025
    Pregnant women with BMI of 30 or more, without diabetes, plus mouse and cell tests
  5. 72 people · Witham 2025
    Adults aged 65 and over with slow walking, weak muscles and prefrailty or frailty (average age 80.4)
  6. 53 people · Konopka 2019
    Older adults, average age 62, starting aerobic exercise training
  7. 47 people · Kulkarni 2020
    Older adults doing resistance exercise training
  8. 20 people · Petrocelli 2023
    Healthy older adults aged 60 and over, not obese
  9. 16 people · McKenzie 2022
    Healthy older adults who had never taken metformin
  10. Population, blood and gene studies
  11. 188,983 people · Rea 2023
    Adults aged 65 and over with type 2 diabetes in Lombardy, Italy, taking mostly metformin and other older drugs
  12. 31,177 people · Wang 2026
    Older adults in three memory-clinic and research cohorts (28,044, 1,708 and 1,425 people), many with dementia
  13. 20,314 people · Antal 2022
    Adults aged 50 to 80 in the UK Biobank, including 1012 with type 2 diabetes (498 on metformin alone)
  14. 4,851 people · Wang 2023
    Swedish people with esophageal cancer, with and without diabetes
  15. 4,278 people · Lambourg 2025
    Scottish adults with type 2 diabetes on metformin who developed stage 4 kidney disease
  16. 4,038 people · Charytan 2019
    People with type 2 diabetes and chronic kidney disease in a darbepoetin trial (591 metformin users, 3447 non-users)
  17. 373 people · Rosell-Díaz 2024
    Adults with no medical history (172), people with long-term type 2 diabetes on metformin (134) or other pills (45), and newly diagnosed people on metformin (22)
  18. 27 people · McCloskey 2020
    Aged mice, plus normal human ovaries from women aged 21 to 82 (two groups of 18 and 9)
  19. People in the study, log scale
    1101001,00010,000100,0001,000,000
  • Points to benefit
  • Mixed
  • No difference
  • No direction
  • Points to harm

Bars use a log scale: each step is ten times more people. Reviews, animal studies and papers with no count in the abstract are not shown.

Who funds this research

Six of 10 trial papers list a company tie: Merck KGaA, Sanofi, Novo Nordisk, Amgen, Rejuvenate Biomed, Dexcom, Dairy Management, Genos, AbbVie, ViiV, CytoDyn and Centaurus Therapeutics. Most of these found no benefit, so confidence did not change.

  • Company stake 6
  • No disclosure in PubMed 1
  • No stake declared 3

Funding rule. A stake is always shown. Confidence is lowered only when every supporting study comes from a party with a stake. "No disclosure in PubMed" means the PubMed record has no conflict-of-interest statement. It does not mean there is no conflict.

What to watch

Large aging trials in people without diabetes

Reviews describe trials, including MILES (Metformin In Longevity Study) and TAME (Targeting Aging with Metformin), designed to test whether metformin can offset aging. Large placebo trials are planned or running, some in healthy people; one uses frailty as its endpoint. No results appear here. Triggle 2022, Glossmann 2019, Espada 2020

Email alerts are coming soon.

All 26 on-topic papers

Each paper shows what it tested, what it found, and who has a stake. Every paper also has its own page that explains how much it counts and how it fits. See every study as a list.

  1. Randomized trial · measured the question itselfUnknown, 1998Lancet (London, England) · PubMed

    Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group.

    753 people · Overweight adults with newly found type 2 diabetes, average age 53

    TestedMetformin aiming for tight blood sugar vs mostly diet alone, median 10.7 years

    Metformin group had risk reductions of 32% (95% CI 13-47, p=0.002) for any diabetes-related endpoint, 42% for diabetes-related death and 36% for all-cause mortality (9-55, p=0.011). Adding metformin to sulphonylurea raised diabetes-related death risk by 96%.

    Points to benefitNo disclosure in PubMedAbstract only

    No disclosure in PubMed.

    Read the study page

  2. Randomized trial · other health measuresWitham et al., 2025The lancet. Healthy longevity · PubMed

    Metformin 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.

    72 people · Adults aged 65 and over with slow walking, weak muscles and prefrailty or frailty (average age 80.4)

    Tested500 mg metformin three times a day vs matching placebo for 4 months

    Walk speed at 4 months was 0·57 m/s with metformin and 0·58 m/s with placebo (adjusted treatment effect 0·001 m/s [95% CI -0·06 to 0·06]; p=0·96). 12 (34%) metformin and three (8%) placebo participants had hospital admissions.

    No differenceCompany stakeAbstract only

    One author gets consultancy fees from Rejuvenate Biomed for sarcopenia trials; trial funded by a public health research institute.

    Read the study page

  3. Randomized trial · other health measuresMunshi et al., 2024Frontiers in public health · PubMed

    Long-term impact of Diabetes Prevention Program interventions on walking endurance.

    1,830 people · Adults at high risk of type 2 diabetes (not yet diabetic at start), tested for walking 20 years later

    TestedMetformin or intense lifestyle program vs placebo for 3 years, then follow-up; 6-minute walk test at 20 years

    Neither intervention changed test completion or distance walked: 362, 364, and 360 m in the lifestyle, metformin, and placebo groups (p = 0.8).

    No differenceCompany stakeAbstract only

    Authors report consulting for Sanofi and Merck KGaA, which supplies metformin; others work or worked for Novo Nordisk and Amgen.

    Read the study page

  4. Randomized trial · other health measuresKonopka et al., 2019Aging cell · PubMed

    Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults.

    53 people · Older adults, average age 62, starting aerobic exercise training

    TestedMetformin (n = 27) vs placebo (n = 26) during 12 weeks of aerobic exercise training

    Metformin attenuated the gain in whole-body insulin sensitivity and VO2 max after exercise training, and abolished the exercise-driven rise in muscle mitochondrial respiration.

    Points to harmCompany stakeAbstract only

    No disclosure in PubMed; grants listed include Dairy Management Inc and Dexcom Inc.

    Read the study page

  5. Randomized trial · lab tests or safetyVinicki et al., 2025GeroScience · PubMed

    Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome.

    White men from Europe aged 29 to 45

    TestedMetformin, testosterone, both, or placebo; blood antibody sugar patterns (a biological age test) tracked over time

    Testosterone changed the antibody sugar pattern compared with placebo. Metformin did not change the sugar patterns by the study's statistical tests.

    No differenceCompany stakeAbstract only

    Several authors own or work for Genos Ltd, a firm that sells glycan analysis tests, including the GlycanAge test.

    Read the study page

  6. Randomized trial · lab tests or safetyHattersley et al., 2025The Journal of physiology · PubMed

    The impact of metformin on placental ageing in humans and mice.

    105 people · Pregnant women with BMI of 30 or more, without diabetes, plus mouse and cell tests

    TestedMetformin vs placebo during pregnancy; afterwards placenta aging signs (telomere length, scarring, gene activity) were checked

    There were no differences between metformin-exposed and control placentas in telomere length, fibrosis or calcification, or in gene activity or methylation. Mouse and cell tests agreed.

    No differenceNo stake declaredAbstract only

    No competing interests declared.

    Read the study page

  7. Randomized trial · lab tests or safetyCorley et al., 2024Aging cell · PubMed

    Cell-type specific impact of metformin on monocyte epigenetic age reversal in virally suppressed older people living with HIV.

    People living with HIV with virus under control and normal blood sugar (two small trials)

    TestedMetformin added vs no added drug for 24 weeks; second trial single arm of 8 people for 4 to 8 weeks; blood cell epigenetic age clocks

    In monocytes, PCPhenoAge and PCGrimAge estimates fell by a mean of 3.53 and 1.84 years from baseline to Week 24 in the metformin arm only. The single-arm trial showed no differences in CD8+ T cells.

    Points to benefitCompany stakeAbstract only

    One author consults for AbbVie, ViiV Healthcare and Cytodyn, sits on Cytodyn board, and holds interests in Ledidi AS (said to be outside this work).

    Read the study page

  8. Randomized trial · lab tests or safetyPetrocelli et al., 2023Aging cell · PubMed

    Disuse-induced muscle fibrosis, cellular senescence, and senescence-associated secretory phenotype in older adults are alleviated during re-ambulation with metformin pre-treatment.

    20 people · Healthy older adults aged 60 and over, not obese

    TestedMetformin vs placebo for 2 weeks before, then during 5 days of bed rest, stopped for 7 days of recovery

    Metformin-treated people had less type-I muscle fiber shrinkage during bed rest, less inflammation signals and less muscle collagen during recovery. Cell aging (senescence) markers were lower too.

    Points to benefitNo stake declaredAbstract only

    No competing interests declared.

    Read the study page

  9. Randomized trial · lab tests or safetyMcKenzie et al., 2022Experimental gerontology · PubMed

    Short-term exposure to a clinical dose of metformin increases skeletal muscle mitochondrial H2O2 emission and production in healthy, older adults: A randomized controlled trial.

    16 people · Healthy older adults who had never taken metformin

    TestedMetformin vs placebo for 2 weeks (8 people each); muscle biopsies checked energy-making parts of cells

    Metformin did not change maximal mitochondrial respiration. Mitochondrial H2O2 emission was higher with metformin (2.59 ± 0.72 SE Fold, P = 0.04) and production too (2.29 ± 0.53 SE Fold, P = 0.02).

    MixedCompany stakeAbstract only

    One author is cofounder, consultant and shareholder of Centaurus Therapeutics.

    Read the study page

  10. Randomized trial · lab tests or safetyKulkarni et al., 2020Aging · PubMed

    Metformin alters skeletal muscle transcriptome adaptations to resistance training in older adults.

    47 people · Older adults doing resistance exercise training

    TestedMetformin (n = 23) vs placebo (n = 24) during 14 weeks of resistance training; muscle gene activity

    Metformin reduced the number of muscle genes changed by training, and an earlier result showed it blunted muscle growth. Genes unique to the metformin group touched aging pathways such as cellular senescence and autophagy.

    MixedNo stake declaredAbstract only

    No competing interests declared.

    Read the study page

  11. Population study: followed a groupWang et al., 2026Age and ageing · PubMed

    Cardiometabolic medication exposures and cognitive outcomes in Alzheimer's disease.

    31,177 people · Older adults in three memory-clinic and research cohorts (28,044, 1,708 and 1,425 people), many with dementia

    TestedSeven classes of heart and sugar medicines, including metformin, linked to change in dementia rating score over time

    Angiotensin-converting enzyme inhibitors and metformin were associated with a slower cognitive decline. Other drug classes had mixed or subgroup-only results.

    Points to benefitNo stake declaredAbstract only

    No competing interests declared.

    Read the study page

  12. Population study: followed a groupLambourg et al., 2025American journal of kidney diseases : the official journal of the National Kidney Foundation · PubMed

    Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study.

    4,278 people · Scottish adults with type 2 diabetes on metformin who developed stage 4 kidney disease

    TestedStopping vs continuing metformin within 6 months of stage 4 kidney disease; death over 3 years

    Stopping metformin was linked to lower 3-year survival (63.7% [95% CI, 60.9-66.6] vs 70.5% [95% CI, 68.0-73.0]; HR, 1.26 [95% CI, 1.10-1.44]). Heart events were similar (HR, 1.05 [95% CI, 0.88-1.26]).

    Points to benefitNo disclosure in PubMedAbstract only

    No disclosure in PubMed.

    Read the study page

  13. Population study: followed a groupRosell-Díaz et al., 2024Metabolism: clinical and experimental · PubMed

    Metformin-induced changes in the gut microbiome and plasma metabolome are associated with cognition in men.

    373 people · Adults with no medical history (172), people with long-term type 2 diabetes on metformin (134) or other pills (45), and newly diagnosed people on metformin (22)

    TestedGut bacteria and blood chemicals in metformin users vs others, linked to memory test scores

    Metformin use went with more A. muciniphila and less R. ilealis gut bacteria. Across all metformin users, this bacteria ratio was not linked to thinking test scores. In men only, it was linked to higher memory scores.

    No differenceCompany stakeAbstract only

    One author gets research support from Biogaia AB and owns shares in Implexion Pharma AB and Roxbiosens Inc.

    Read the study page

  14. Population study: cases vs controlsRea et al., 2023Cardiovascular diabetology · PubMed

    Adherence to antidiabetic drug therapy and reduction of fatal events in elderly frail patients.

    188,983 people · Adults aged 65 and over with type 2 diabetes in Lombardy, Italy, taking mostly metformin and other older drugs

    TestedHow closely people took their diabetes pills vs risk of death over up to 6 years (cases who died vs matched controls)

    Higher adherence to diabetes drugs went with lower all-cause death risk in all clinical groups and ages except frail patients aged 85 and over. The benefit was smaller in frail patients.

    Points to benefitCompany stakeAbstract only

    Authors report research projects funded by, and fees from, drug companies including Novartis, GSK, Roche, Amgen, BMS and Servier.

    Read the study page

  15. Population study: followed a groupWang et al., 2023JNCI cancer spectrum · PubMed

    Diabetes, metformin use, and survival in esophageal cancer: a population-based cohort study.

    4,851 people · Swedish people with esophageal cancer, with and without diabetes

    TestedDiabetes status and metformin use vs death over follow-up

    Compared with diabetic cancer patients not on metformin, metformin users had lower all-cause mortality (HR = 0.86, 95% CI = 0.75 to 1.00). Higher metformin doses went with lower death risk (Ptrend = .04).

    Points to benefitNo stake declaredAbstract only

    No competing interests declared.

    Read the study page

  16. Population study: one-time surveyAntal et al., 2022eLife · PubMed

    Type 2 diabetes mellitus accelerates brain aging and cognitive decline: Complementary findings from UK Biobank and meta-analyses.

    20,314 people · Adults aged 50 to 80 in the UK Biobank, including 1012 with type 2 diabetes (498 on metformin alone)

    TestedBrain scans and thinking tests in people with diabetes vs without; then metformin-treated vs untreated people with diabetes

    Type 2 diabetes was linked to brain shrinkage and weaker thinking, overlapping with aging effects. Metformin treatment status was not associated with improved neurocognitive outcomes.

    No differenceCompany stakeAbstract only

    One author sits on a Novo Nordisk data monitoring committee; others report fees from drug firms, said to be unrelated to this work.

    Read the study page

  17. Population study: followed a groupMcCloskey et al., 2020Clinical cancer research : an official journal of the American Association for Cancer Research · PubMed

    Metformin Abrogates Age-Associated Ovarian Fibrosis.

    27 people · Aged mice, plus normal human ovaries from women aged 21 to 82 (two groups of 18 and 9)

    TestedLooked at scarring (fibrosis) in ovaries by age and compared ovaries from metformin users with others

    Fibrosis developed in older mouse and human ovaries (n = 27). Metformin use was associated with attenuated CD8+ T-cell infiltration and a reduced CD206+:CD68+ cell ratio.

    Points to benefitNo disclosure in PubMedAbstract only

    No disclosure in PubMed.

    Read the study page

  18. Population study: followed a groupCharytan et al., 2019Diabetes, obesity & metabolism · PubMed

    Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease.

    4,038 people · People with type 2 diabetes and chronic kidney disease in a darbepoetin trial (591 metformin users, 3447 non-users)

    TestedMetformin users vs non-users at the start of the trial, followed for death and heart events

    Metformin use was linked to lower all-cause death (HR, 0.49; 95% CI, 0.36-0.69), heart death (HR, 0.49; 95% CI, 0.32-0.74) and heart events (HR, 0.67, 95% CI, 0.51-0.88). Two cases of lactic acidosis were seen.

    Points to benefitNo disclosure in PubMedAbstract only

    No disclosure in PubMed.

    Read the study page

  19. Animal studySun et al., 2022Experimental gerontology · PubMed

    Characterization of cellular senescence in doxorubicin-induced aging mice.

    Mice given the drug doxorubicin to speed up aging signs

    TestedDoxorubicin 5 mg/kg to induce aging markers, then metformin treatment

    Some markers of senescent cells (p21WAF1/CIP1, p16INK4A, and γH2AX) were upregulated by doxorubicin and then counteracted by metformin treatment.

    Points to benefitNo disclosure in PubMedAbstract only

    No disclosure in PubMed.

    Read the study page

  20. Animal studyEspada et al., 2020Nature metabolism · PubMed

    Loss of metabolic plasticity underlies metformin toxicity in aged Caenorhabditis elegans.

    Roundworms (C. elegans) of different ages and human cells grown in dishes

    TestedMetformin given early or late in life, and to young vs old cells

    Metformin shortened lifespan when provided in late life, contrary to its positive effects in young organisms. In aged worms and late-passage human cells it caused lethal ATP exhaustion.

    Points to harmNo disclosure in PubMedAbstract only

    No disclosure in PubMed.

    Read the study page

  21. Animal studyMartin-Montalvo et al., 2013Nature communications · PubMed

    Metformin improves healthspan and lifespan in mice.

    Middle-aged male mice

    TestedMetformin at 0.1% in food or 1% in food for life vs normal food

    Long-term 0.1% w/w metformin starting at middle age extended healthspan and lifespan in male mice, while the higher 1% w/w dose was toxic. It improved physical performance and insulin sensitivity.

    Points to benefitNo disclosure in PubMedAbstract only

    No disclosure in PubMed.

    Read the study page

  22. Pooled review (meta-analysis)Li et al., 2022Clinics and research in hepatology and gastroenterology · PubMed

    Impact of metformin use on risk and mortality of hepatocellular carcinoma in diabetes mellitus.

    People with diabetes, with and without metformin, studied for liver cancer

    TestedMetformin use vs non-use in diabetes, for liver cancer risk and death from liver cancer

    Metformin use was linked to lower liver cancer risk (OR/RR = 0.59, 95% CI 0.51-0.68) and lower all-cause death in those with liver cancer (HR = 0.74, 95% CI 0.66-0.83).

    Points to benefitNo stake declaredAbstract only

    No competing interests declared.

    Read the study page

  23. Pooled review (meta-analysis)Campbell et al., 2017Ageing research reviews · PubMed

    Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis.

    53 studies · Mostly people with diabetes taking metformin, compared with people without diabetes or with diabetes on other drugs

    TestedMetformin use vs no diabetes, or vs other diabetes drugs, for death and age-related disease

    Diabetics on metformin had lower all-cause death than non-diabetics (HR=0.93, 95%CI 0.88-0.99) and than diabetics on other drugs (HR=0.72, 95%CI 0.65-0.80). Cancer was lower than in non-diabetics (rate ratio=0.94, 95%CI 0.92-0.97).

    Points to benefitNo disclosure in PubMedAbstract only

    No disclosure in PubMed.

    Read the study page

  24. Pooled review (meta-analysis)Maruthur et al., 2016Annals of internal medicine · PubMed

    Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis.

    204 studies · Adults with type 2 diabetes

    TestedDiabetes drugs alone or with metformin, compared head to head (179 trials, 25 observational studies)

    Cardiovascular death was lower with metformin than with sulfonylureas. Evidence on all-cause death, heart events and small-vessel complications was insufficient or of low strength.

    MixedNo disclosure in PubMedAbstract only

    No disclosure in PubMed. Funded by the Agency for Healthcare Research and Quality.

    Read the study page

  25. Opinion or narrative reviewTriggle et al., 2022Metabolism: clinical and experimental · PubMed

    Metformin: Is it a drug for all reasons and diseases?

    People and lab models studied for metformin use beyond diabetes, including aging

    TestedReview of what metformin does and whether it helps in many diseases, including aging (MILES and TAME trials are planned)

    The authors conclude metformin's main benefits come from lowering blood sugar and improving insulin response, which lowers risk of some diseases and may add to healthy years of life. Some benefits, like better blood vessel function, may not depend on blood sugar.

    No weight on the ladderNo disclosure in PubMedAbstract only

    No disclosure in PubMed.

    Read the study page

  26. Opinion or narrative reviewGlossmann et al., 2019Gerontology · PubMed

    Metformin and Aging: A Review.

    Aging people and diabetics (review of studies and plans)

    TestedReview of the case for metformin as an anti-aging drug

    Review says the anti-aging idea rests on lab work in lower animals and many looking-back studies in people with diabetes. Large placebo trials are planned. It notes vitamin B12 and B6 shortfalls and possible harm for people who exercise to stay fit.

    No weight on the ladderNo disclosure in PubMedAbstract only

    No disclosure in PubMed.

    Read the study page

34 papers we read and set aside as off topic
  1. Tsapas et al., 2020. Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis. (pooled review (meta-analysis))
  2. Li et al., 2021. Cardiovascular outcomes associated with SGLT-2 inhibitors versus other glucose-lowering drugs in patients with type 2 diabetes: A real-world systematic review and meta-analysis. (pooled review (meta-analysis))
  3. Voros et al., 2026. A Systematic Review on GLP-1 Receptor Agonists in Reproductive Health: Integrating IVF Data, Ovarian Physiology and Molecular Mechanisms. (systematic review)
  4. Volke et al., 2022. Systematic review and meta-analysis of head-to-head trials comparing sulfonylureas and low hypoglycaemic risk antidiabetic drugs. (pooled review (meta-analysis))
  5. Kanie et al., 2021. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. (pooled review (meta-analysis))
  6. Wang et al., 2023. Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study. (population study: followed a group)
  7. Inzucchi et al., 2020. Are the cardiovascular and kidney benefits of empagliflozin influenced by baseline glucose-lowering therapy? (randomized trial)
  8. Chia et al., 2014. GIP contributes to islet trihormonal abnormalities in type 2 diabetes. (population study: cases vs controls)
  9. Bethel et al., 2020. Exploring the Possible Impact of Unbalanced Open-Label Drop-In of Glucose-Lowering Medications on EXSCEL Outcomes. (randomized trial)
  10. Sabini et al., 2023. MyMD-1 Improves Health Span and Prolongs Life Span in Old Mice: A Noninferiority Study to Rapamycin. (animal study)
  11. Mensà et al., 2019. Circulating miR-146a in healthy aging and type 2 diabetes: Age- and gender-specific trajectories. (population study: one-time survey)
  12. Seliger et al., 2020. Baseline Characteristics and Patient-Reported Outcomes of ADPKD Patients in the Multicenter TAME-PKD Clinical Trial. (randomized trial)
  13. Hallows et al., 2021. Association of Baseline Urinary Metabolic Biomarkers with ADPKD Severity in TAME-PKD Clinical Trial Participants. (population study: one-time survey)
  14. Perrone et al., 2021. Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD). (randomized trial)
  15. Yerevanian et al., 2019. Metformin: Mechanisms in Human Obesity and Weight Loss. (opinion or narrative review)
  16. De Broe et al., 2018. Renoprotective Effects of Metformin. (opinion or narrative review)
  17. Xie et al., 2023. Comparative effectiveness of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and sulfonylureas on risk of major adverse cardiovascular events: emulation of a randomised target trial using electronic health records. (population study: followed a group)
  18. Sarkar et al., 2024. Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights. (opinion or narrative review)
  19. Sun et al., 2025. SGLT2 inhibitors vs. metformin for Parkinson's disease risk reduction in type 2 diabetes. (population study: followed a group)
  20. Triggle et al., 2023. Repurposing Metformin for Vascular Disease. (opinion or narrative review)
  21. Tatum et al., 2026. Survival and Recurrence With GLP-1 Receptor Agonists in Breast Cancer. (population study: followed a group)
  22. Zhang et al., 2023. Oral Metformin Inhibits Choroidal Neovascularization by Modulating the Gut-Retina Axis. (animal study)
  23. Prud'homme et al., 2022. Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations. (opinion or narrative review)
  24. Cai et al., 2023. Metformin potentiates nephrotoxicity by promoting NETosis in response to renal ferroptosis. (animal study)
  25. Chen et al., 2022. Metformin Attenuates UVA-Induced Skin Photoaging by Suppressing Mitophagy and the PI3K/AKT/mTOR Pathway. (cell study)
  26. Thomas et al., 2017. Metformin; a review of its history and future: from lilac to longevity. (opinion or narrative review)
  27. Heneka et al., 2015. Effect of pioglitazone medication on the incidence of dementia. (population study: followed a group)
  28. Allan et al., 2025. Glucagon-like Peptide-1 Receptor Agonist Impact on Chronic Ocular Disease Including Age-Related Macular Degeneration. (population study: followed a group)
  29. Suissa et al., 2021. The modifying effects of adiposity on the cardiovascular safety of sulphonylureas. (population study: followed a group)
  30. Delhaes et al., 2026. Plasma Proteome Profiling of Centenarian Across Switzerland Reveals Key Youth-Associated Proteins. (population study: one-time survey)
  31. Hartwig et al., 2021. Metformin Attenuates ROS via FOXO3 Activation in Immune Cells. (cell study)
  32. Deng et al., 2022. Emulating the GRADE trial using real world data: retrospective comparative effectiveness study. (population study: followed a group)
  33. Sun et al., 2025. SGLT2is Versus Metformin for Delirium Prevention in Type 2 Diabetes: A Real-World, Head- to-Head Comparative Study. (population study: followed a group)
  34. Bidulka et al., 2024. Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data. (population study: followed a group)

Words on this page

Hazard ratio (HR)
Compares how often something happened in two groups over time. 1 means no difference. 0.80 means 20% lower risk; 1.20 means 20% higher.
Relative risk (RR)
Compares the risk in two groups. 1 means no difference. 0.85 means 15% lower risk.
95% CI (confidence interval)
The range where the true result likely lies. If the range includes no effect (1 for ratios, 0 for differences), the result is not clear.
p-value (p =)
How likely a result this large would be by chance if there were no real effect. Below 0.05 is usually called a clear result.
Placebo
A dummy pill or fake treatment, so people do not know which group they are in.
Pooled review (meta-analysis)
A study that combines the results of many earlier studies to get one overall answer.
Cohort study
A study that follows a large group of people over years. It shows links, not causes.
Marker
A lab or scan result that stands in for a health outcome. A better marker does not always mean better health.

How the short answer is set

Fixed rules turn the studies into the short answer, so the same studies always give the same answer. The rules start from GRADE, a standard system for rating evidence, in plain language.

ConfidenceWhat it means
HighWe are confident the answer is right.
ModerateThe answer is probably right, but it could change.
Low (this page)The answer may well change.
Very lowAny answer is very uncertain.
Not tested in peopleOnly cell or animal studies exist.

Why low here

  • The only trial measuring death (UKPDS 34) was in people with diabetes.
  • Trials in people without diabetes measured walking, muscle or blood markers, not aging itself.
  • Most trials were small, 16 to 72 people, apart from one walking follow-up.
  • Results disagree: studies in diabetes link metformin to fewer deaths; walking trials found no benefit.

Hard limit used. No human trial measured aging, frailty or death in people without diabetes, so the answer cannot say metformin slows aging in them.

How this page was made

Label

Search
PubMed, Nov 14, 2026. Searches written by Claude Opus 5.5; papers ranked by PubMed
First read of all 60 papers
Claude Sonnet
Independent second read
Claude Haiku
Disagreements settled by
Claude Opus 5.5
Page text written by
Claude Opus 5.5
Charts
Drawn by code from the study records
Source check by a person
Not yet. Required before search engines may list this page.
Expert review
No
Papers read in full
0 of 60; all from PubMed abstracts
Method
v0.2, created Nov 14, 2026
102numbers in the two reads checked against the abstracts. 2 were not found as written and were fixed.
29key numbers on this page checked again against the papers they cite. All were found.
25 / 60papers where both reads agreed on all ten checked fields.
9fields corrected by the reviewer after reading the abstract.

Search. We ran four PubMed searches for metformin and aging, frailty and death in people without diabetes: pooled and systematic reviews since 2012 (10 of 80), trials in people (22 of 51), population studies (22 of 285), animal studies (6 of 260). The first number is how many papers we read; the second is how many PubMed found. We took the ones PubMed ranks as most relevant. See the full PubMed search. Of the 60 papers read, 26 were on topic.

Limits. Digestery reads at most about 60 papers per question, so large fields are sampled, not covered in full. Abstracts can leave out key details, such as side effects and funding.

Review queue

These items wait for a person. Search engines are asked not to list the page until the first one is done.

  1. OpenThe short answer is new. It waits for a source check by a person.
  2. OpenMcKenzie 2022 and Petrocelli 2023 share registration NCT03107884 (2-week metformin, older adults); likely one trial reported twice. Check before counting trials.
  3. OpenRea 2023 studies adherence to all diabetes drugs (mostly metformin), not metformin alone; kept relevant, but check it belongs in this topic.
  4. OpenSun 2025 and Sun 2025 (SGLT2 drugs vs metformin; metformin users fared worse) kept off-topic as active-comparator studies; confirm this rule.
  5. OpenWitham 2025 (MET-PREVENT) abstract does not say whether participants had diabetes; check full text.
  6. OpenHattersley 2025 (placental ageing in pregnancy) and McCloskey 2020 (ovary tissue markers, metformin users not described) kept relevant as indirect; borderline.
  7. OpenStake marked company for Corley 2024, Vinicki 2025 and McKenzie 2022, though named firms are not shown to sell metformin; check the stake rule.
  8. OpenSun 2025 abstract gives death aHR 0.85 with 95% CI 0.87-0.88, which excludes the estimate; likely an abstract error.
  9. OpenParticipant numbers missing from abstracts of Corley 2024 and Vinicki 2025; doses missing for Petrocelli 2023, Konopka 2019 and McKenzie 2022.

Page history

DateChangeReason
Nov 14, 2026Page created from 60 papers.First version of the page.

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A flag must point to a source: the passage in the paper, or a link to a study this page missed. A flag starts a new check. Votes never change a page.