Human lifespan evidence: none
Classification
Intervention class: Biguanide antidiabetic drug ('mTOR-adjacent' -- not a direct or selective mTOR inhibitor)
Aliases: Glucophage (brand)
Relationship to mTOR: NOT a direct or selective mTOR inhibitor. Primary mechanism is AMPK activation / cellular energy-sensing and mitochondrial complex I inhibition; AMPK activation secondarily inhibits mTORC1 via TSC2 (see /ampk, /tsc1-tsc2). Grouped in this evidence map as an 'mTOR-adjacent' intervention, not a rapalog-class compound.
Mechanism summary: Activates AMPK and inhibits mitochondrial complex I; AMPK activation is one of several inputs that can inhibit mTORC1 via TSC2, but this is an indirect, energy-sensing route rather than a direct mTOR-binding mechanism like rapamycin's.
Regulatory status
FDA-approved prescription antidiabetic drug (type 2 diabetes). NOT approved for any anti-aging/longevity indication in any jurisdiction as of this dataset's literature-search date. TAME (Targeting Aging with Metformin) is a planned/registered trial intended to test an aging-related composite endpoint, but has NOT reported results as of the brief's 2026-07-11 literature-search date.
Evidence per species / population (5-qualifier claim format)
Mouse (dietary metformin, dose-dependent) Tier 6 · Single-lab animal lifespan verification: verified_2026-07-11
1. Species / populationMice, dietary metformin dosing studies
2. Exposure, route, schedule0.1% metformin in diet
3. Comparator & durationControl diet; lifespan follow-up
4. Endpoint & numeric resultMedian lifespan increased by approximately +5.83% in MALE mice at the 0.1% dietary dose; a higher 1% dietary dose was TOXIC (net negative), a non-monotonic dose-response
5. What this study did NOT establishDid not test humans; does not establish a safe or effective human dose by extrapolation. The same compound was toxic in mice at a roughly 10-fold higher dietary dose, underscoring that dose-response is not linear or directly extrapolable.
Human (MILES trial, short-term mechanistic) — QUALITATIVE ENTRY: population (n=14), dose (1700 mg/day), and duration (6 weeks) are recorded, but no specific numeric endpoint result is supplied in the sourcing material; none is fabricated here. Tier 8 · Human acute mechanistic verification: verified_2026-07-11
1. Species / populationOlder adults, MILES trial, n=14
2. Exposure, route, scheduleMetformin 1700 mg/day, oral, for 6 weeks
3. Comparator & durationPlacebo; 6-week mechanistic study (not a lifespan or long-term clinical-outcome trial)
4. Endpoint & numeric resultMechanistic/molecular endpoints assessed (e.g. gene-expression/pathway signatures); the sourcing brief does not supply a specific quantitative effect-size figure for this dataset
5. What this study did NOT establishSmall (n=14), short-duration (6-week) mechanistic study; does not establish clinical benefit, functional outcome, or lifespan effect.
Human (MASTERS trial: metformin + resistance exercise) Tier 2 · Human clinical/functional RCT verification: verified_2026-07-11
1. Species / populationOlder adults undergoing supervised resistance-exercise training, MASTERS trial
2. Exposure, route, scheduleMetformin, oral, concurrent with a structured resistance-training program
3. Comparator & durationPlacebo + same resistance-training program
4. Endpoint & numeric resultMetformin BLUNTED (reduced) resistance-training-induced muscle mass/strength gains relative to placebo + exercise -- a negative interaction, not a benefit
5. What this study did NOT establishDid not test lifespan. Demonstrates a negative interaction between metformin and exercise-induced muscle adaptation in older adults; does not generalize to metformin's effects outside the resistance-training context or in non-exercising populations.
Human (TAME trial, planned/registered, no results) Tier 10 · Hypothesis / unreplicated verification: verified_2026-07-11
1. Species / populationAdults, TAME (Targeting Aging with Metformin) trial, planned enrollment greater than 3000 participants
2. Exposure, route, scheduleMetformin, oral, per planned trial protocol
3. Comparator & durationPlacebo (planned); trial design, not yet completed as of 2026-07-11
4. Endpoint & numeric resultNO RESULTS AVAILABLE as of this dataset's 2026-07-11 literature-search date -- TAME is a planned/registered trial, not a completed study
5. What this study did NOT establishNothing yet. This entry exists to make explicit that no completed 'metformin extends human lifespan' trial result exists, contrary to frequent informal claims.
Negative / null / conflicting findings
1% dietary metformin was toxic in mice (net negative at the higher dose), illustrating non-monotonic dose-response. [study record] verification: verified_2026-07-11
MASTERS: metformin blunted resistance-training-induced muscle adaptation -- a counter-example to a general 'metformin helps healthy aging' framing. [study record] verification: verified_2026-07-11
TAME has not reported results as of the brief's 2026-07-11 literature-search date. [study record] verification: verified_2026-07-11
Safety
Safety notes
Metformin is an FDA-approved prescription antidiabetic drug. Approved-use labeling covers gastrointestinal effects and a rare lactic-acidosis risk in susceptible populations (e.g. renal impairment), among other standard warnings. Safety of any off-label longevity dosing regimen has not been established and is not published on this site.
Source: Metformin (Glucophage) prescribing information (FDA/DailyMed) (regulatory label) verification: verified_2026-07-11
Editorial policy: This site publishes no 'longevity dose', no cycling protocol, no dosing calculator, and no acquisition guidance for metformin.
Funding / conflict of interest
Funding sources and conflict-of-interest disclosures for individual studies are not reproduced here pending primary-source verification; see each linked study record.
Related study records
Version 0.2.0-mvp · literature search date 2026-07-11 · editorial owner Nabus Research