{ "checked": "2026-10-26", "page": "https://jabbitapp.com/research/metformin-longevity-anti-aging-tame-evidence-teardown.html", "label": { "source": "DailyMed metformin hydrochloride tablet, film coated, Zydus Pharmaceuticals USA Inc., setid c82a10fa-1e8e-46b6-890a-737de3f34ee1, SPL version 17, effective 2026-07-15", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfoBySetId.cfm?setid=c82a10fa-1e8e-46b6-890a-737de3f34ee1", "quotes": [ "WARNING: LACTIC ACIDOSIS", "Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias.", "Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, hepatic impairment", "Metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus.", "Metformin may lower vitamin B12 levels.", "Increased risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue.", "the most common adverse reactions (>5.0%) are diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache." ], "boxed_warning": "lactic acidosis" }, "registry": { "query": "ClinicalTrials.gov API v2, query.intr=metformin, query.cond=aging OR frailty OR sarcopenia OR longevity OR healthspan", "records": 31, "status_counts": { "RECRUITING": 5, "COMPLETED": 13, "TERMINATED": 2, "UNKNOWN": 5, "ACTIVE_NOT_RECRUITING": 2, "NOT_YET_RECRUITING": 1, "ENROLLING_BY_INVITATION": 1, "WITHDRAWN": 2 }, "records_with_posted_results": [ "NCT01804049", "NCT02308228", "NCT02432287", "NCT02570672", "NCT03309007", "NCT03451006", "NCT03861767", "NCT04221750", "NCT04264897" ], "tame": { "phrase_search": "\"Targeting Aging with Metformin\" returned only NCT05651620 (CALERIE Legacy Study)", "acronym_search": "TAME AND metformin returned NCT05651620 and NCT02656017 (a polycystic kidney disease trial that shares the acronym)", "note": "We found no ClinicalTrials.gov record for the aging trial called TAME." }, "selected": { "NCT02570672": [ "COMPLETED", 141, "The University of Texas Health Science Center at San Antonio", "2024-02-07", true, "2016-04" ], "NCT02432287": [ "COMPLETED", 16, "Albert Einstein College of Medicine", "2015-09", true, "2014-10" ], "NCT04221750": [ "COMPLETED", 114, "VA Office of Research and Development", "2025-07-31", true, "2021-05-14" ], "NCT02308228": [ "COMPLETED", 109, "Philip Kern", "2017-12-14", true, "2015-01-14" ], "NCT01101438": [ "COMPLETED", 3649, "Canadian Cancer Trials Group", "2021-09-21", true, "2010-08-13" ], "NCT02915198": [ "RECRUITING", 7410, "VA Office of Research and Development", "2029-09-28", false, "2023-04-03" ], "NCT04264897": [ "COMPLETED", 166, "Oklahoma Medical Research Foundation", "2025-03-12", true, "2020-07-29" ], "NCT07302932": [ "COMPLETED", 112, "Diabetes Foundation, India", "2025-01-30", false, "2023-02-01" ], "NCT03309007": [ "COMPLETED", 25, "University of New Mexico", "2020-08-20", true, "2017-09-01" ], "NCT01804049": [ "COMPLETED", 120, "VA Office of Research and Development", "2018-08-31", true, "2014-04-08" ] } }, "pubmed": { "human_lifespan": { "count": 5, "idlist": [ "37675817", "35914953", "28732480", "25921843", "24194506" ], "query": "metformin[tiab] AND (lifespan[tiab] OR life span[tiab] OR longevity[tiab]) AND randomized controlled trial[pt]", "note": "None of the 5 records measured lifespan in people (one is a mouse study, one a design paper)." } }, "key_trials": [ { "trial": "Diabetes prevention (DPP), 2002", "n": 3234, "result": "Main goal met; lifestyle did better", "id": "11832527" }, { "trial": "Breast cancer (MA.32), 2022", "n": 3649, "result": "Main goal missed", "id": "35608580" }, { "trial": "Strength training, 65+ (MASTERS), 2019", "n": 94, "result": "Less muscle gain than placebo", "id": "31557380" }, { "trial": "Frail, mean age 80 (MET-PREVENT), 2025", "n": 72, "result": "Main goal missed; poorly tolerated", "id": "40147475" }, { "trial": "Obese 65+ with lifestyle (DEMFOS), 2026", "n": 114, "result": "No added benefit", "id": "42532077" }, { "trial": "HIV, epigenetic age (METFORAGING), 2026", "n": 40, "result": "Main goal missed", "id": "42023167" }, { "trial": "Prediabetes, frailty (preprint), 2026", "n": 145, "result": "Mixed; not peer reviewed", "id": "42620010" } ], "key_trials_total_n": 7348, "abstract_quotes": { "23900241": { "title": "Metformin improves healthspan and lifespan in mice", "journal": "Nat Commun", "year": "2013", "quotes": [ "starting at middle age extends healthspan and lifespan in male mice", "Treatment with metformin mimics some of the benefits of calorie restriction", "raise the possibility of metformin-based interventions to promote healthy aging" ] }, "27312235": { "title": "Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer", "journal": "Aging Cell", "year": "2016", "quotes": [ "Metformin alone,", "did not significantly extend lifespan.", "robustly extended lifespan, suggestive of an added benefit", "based on historical comparison with earlier studies of rapamycin given alone" ] }, "38630424": { "title": "The Gehan test identifies life-extending compounds overlooked by the log-rank test in the NIA Interventions Testing Program: Metformin, Enalapril, caffeic acid phenethyl ester, green tea extract, and 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride", "journal": "Geroscience", "year": "2024", "quotes": [ "We therefore reanalyzed all data collected by the ITP from 2004-2022 using the Gehan test", "Three (metformin, enalapril, and 17-DMAG) were only effective in males" ] }, "27304507": { "title": "Metformin as a Tool to Target Aging", "journal": "Cell Metab", "year": "2016", "quotes": [ "will be tested in the TAME (Targeting Aging with Metformin) trial" ] }, "25041462": { "title": "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", "journal": "Diabetes Obes Metab", "year": "2014", "quotes": [ "We identified 78,241 subjects treated with metformin", "Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non-diabetic controls." ] }, "36287641": { "title": "Reassessing the evidence of a survival advantage in Type 2 diabetes treated with metformin compared with controls without diabetes: a retrospective cohort study", "journal": "Int J Epidemiol", "year": "2022", "quotes": [ "these associations were attenuated to 1.32 (95% CI: 1.16, 1.50) and 1.64 (95% CI: 1.10, 2.46), respectively.", "Treatment initiation by metformin monotherapy in Type 2 diabetes was not associated with survival equal or superior to that of the general population without diabetes." ] }, "40388602": { "title": "Comparative Effectiveness of Metformin Versus Sulfonylureas on Exceptional Longevity in Women With Type 2 Diabetes: Target Trial Emulation", "journal": "J Gerontol A Biol Sci Med Sci", "year": "2025", "quotes": [ "Among 438 propensity score-matched women with type 2 diabetes", "(hazard ratio, 0.70; 95% CI: 0.56-0.88)", "causality cannot be inferred" ] }, "11832527": { "title": "Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin", "journal": "N Engl J Med", "year": "2002", "quotes": [ "We randomly assigned 3234 nondiabetic persons", "metformin by 31 percent", "The lifestyle intervention reduced the incidence by 58 percent", "The lifestyle intervention was more effective than metformin." ] }, "35608580": { "title": "Effect of Metformin vs Placebo on Invasive Disease-Free Survival in Patients With Breast Cancer: The MA.32 Randomized Clinical Trial", "journal": "JAMA", "year": "2022", "quotes": [ "enrolled 3649 patients with high-risk nonmetastatic breast cancer", "(21.5% vs 17.5%, respectively, P = .003)", "the addition of metformin vs placebo to standard breast cancer treatment did not significantly improve invasive disease-free survival" ] }, "31557380": { "title": "Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double-blind, placebo-controlled, multicenter trial: The MASTERS trial", "journal": "Aging Cell", "year": "2019", "quotes": [ "placebo gained more lean body mass (p = .003) and thigh muscle mass (p < .001) than metformin", "metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals" ] }, "29383869": { "title": "Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults", "journal": "Aging Cell", "year": "2018", "quotes": [ "~70-year-old participants (n = 14)", "treated with 6 weeks each of metformin and placebo", "This study provides the first evidence that, in older adults, metformin has metabolic and nonmetabolic effects linked to aging." ] }, "40147475": { "title": "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", "journal": "Lancet Healthy Longev", "year": "2025", "quotes": [ "72 participants were randomly assigned", "Mean age was 80·4 years", "p=0·96", "108 adverse events occurred in 35 (100%) of 35 participants who received metformin and 77 adverse events occurred in 33 (92%) of 36 participants who received placebo", "12 (34%) of 35 participants had hospital admissions in the metformin group versus three (8%) of 36 participants in the placebo group", "Metformin did not improve 4-m walk speed and was poorly tolerated in this population." ] }, "42532077": { "title": "Metformin added to lifestyle intervention for physical function in older adults with obesity (DEMFOS trial): a randomised controlled trial", "journal": "Lancet Healthy Longev", "year": "2026", "quotes": [ "114 were included in this study", "(0·1 points, -1·2 to 1·4; p=0·92)", "metformin does not provide additional improvement in physical function", "These results support prioritising lifestyle-based strategies to improve functional outcomes in this population." ] }, "42023167": { "title": "Metformin and epigenetic age in non-diabetic older people with HIV in Madrid (METFORAGING): a double-blind, randomised, placebo-controlled, pilot trial", "journal": "EClinicalMedicine", "year": "2026", "quotes": [ "40 were randomly assigned", "Enrolment was closed at 40 participants because of slow recruitment", "-1.02 years (95% confidence interval [CI] -5.30 to 3.26; p = 0.627)", "no significant difference was noted in the primary outcome" ] }, "42609624": { "title": "Metformin and Weight Changes in Non-diabetic Older People With HIV (METFORAGING): A Double-Blind, Randomized, Placebo-Controlled, Pilot Trial", "journal": "Open Forum Infect Dis", "year": "2026", "quotes": [ "(between-group difference -2.8 kg [95% CI -5.2 to -0.4]; P = .025)", "After discontinuation, weight in the metformin group returned toward baseline" ] }, "42620010": { "title": "A Randomized Clinical Trial of Metformin to Reduce Frailty in Older Adults with Glucose Intolerance", "journal": "medRxiv", "year": "2026", "quotes": [ "145 non-frail or pre-frail older adults", "an upward trajectory in year 1", "when assessing effect on Fried score without the weight loss criterion, no difference was observed", "metformin caused a steady improvement in the frailty index", "Metformin was well tolerated.", "metformin led to a significant reduction in the deficit accumulation frailty index but not the Fried frailty phenotype" ] }, "42692117": { "title": "Metformin therapy increases leukocyte telomere length, telomerase activity, and longevity gene expression in Asian Indians with prediabetes: A 24-week participant-blind, outcome-assessor-blinded randomized controlled trial", "journal": "Mech Ageing Dev", "year": "2026", "quotes": [ "127 participants met the eligibility criteria", "for 24 weeks", "29.6% vs 4.4% elongation", "the marked LTL response requires cautious interpretation" ] }, "42841129": { "title": "Impact of metformin use on neurocognitive functions in older people: a systematic review and meta-analysis", "journal": "Dement Neuropsychol", "year": "2026", "quotes": [ "Thirteen articles met the eligibility criteria", "five provided sufficient data for the meta-analysis", "metformin has a small but positive effect on overall cognitive function in older adults" ] }, "34865016": { "title": "Antecedent Metabolic Health and Metformin (ANTHEM) Aging Study: Rationale and Study Design for a Randomized Controlled Trial", "journal": "J Gerontol A Biol Sci Med Sci", "year": "2022", "quotes": [ "The antidiabetic medication metformin has been proposed to be the first drug tested to target aging and extend healthspan in humans.", "it is not clear if these protective effects apply to those free of age-related disease" ] }, "42710703": { "title": "Geroprotective potential of anti-diabetic medications: Bridging type 2 diabetes and accelerated aging", "journal": "Pharmacol Res", "year": "2026", "quotes": [ "translational relevance remains uncertain due to model heterogeneity, limited randomized clinical evidence, and insufficient long-term follow-up" ] } }, "conflict_statements": { "38630424": "The authors declare no competing interests.", "40388602": "declare no conflicts of interest.", "31557380": "The authors have no conflict of interests to disclose.", "40147475": "MDW reports receiving consultancy fees from Rejuvenate Biomed for work on sarcopenia trials.", "42532077": "We declare no competing interests.", "42532078": "MDW has received consultancy fees from Rejuvenate Biomed, Istesso, and Novo Nordisk for sarcopenia trial design", "42841129": "The authors report no conflicts of interest." }, "analysis": { "note": "Jabbit analysis. Metformin is a cheap, decades-old prescription diabetes drug. In mice, one NIA lab study reported longer life in males, but the multi-site NIA Interventions Testing Program found metformin alone did not significantly extend lifespan (a 2024 reanalysis with a different test found a male-only effect). In people, the famous survival signal comes from observational data: a 2014 UK study found people with diabetes on metformin outlived matched people without diabetes, but a 2022 Danish register study including twins did not find that. No human trial has measured lifespan; TAME, proposed in 2016, has no ClinicalTrials.gov record. Randomized trials in older adults (MASTERS, MET-PREVENT, DEMFOS, METFORAGING) mostly missed their main goals, and MASTERS found less muscle gain from strength training. Metformin carries a boxed warning for lactic acidosis and can lower vitamin B12." } }