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Metformin

Aliases: Glucophage

Last verified: 2026-09-23

Approved drugStrong evidenceSmall moleculesHigh interest

The short version

Metformin is the most prescribed antidiabetic in history — and an unusual 'longevity' candidate. Epidemiological data (TAME inspiration) suggest diabetics on metformin live longer than non-diabetics; MILES and small RCTs show metabolic and inflammatory signals. But the TAME trial (Targeting Aging with Metformin) — the first large trial designed to show slowed aging — is still running. Until then: metformin is an excellent diabetes drug, and a 'drug for aging' remains a hypothesis.

Identity & type

Molecular type
small-molecule
Sequence / structure
— (bigvanid)
Molecular weight
~129 Da
Formula
C4H11N5
Origin
Biguanide derivative, type 2 diabetes drug since the 1950s; mitochondrial complex I inhibitor.

Mechanism of action

AMPK activation, mitochondrial complex-I inhibition, reduced hepatic gluconeogenesis; possibly via gut microbiome.

Dosing & routes

Official / clinical context

Approved drug — indications, dosing and warnings are defined by the official label. 500–2000 mg/day.

Regulator-approved labeling and published study designs — never a recommendation.

Community-reported practice

500–2000 mg/day. In diabetics: stable glycemia; in longevity circles: mild metabolic effects, but some avoid it due to possibly blunted training adaptations.

Unverified self-reports. Not medical advice. Not endorsement.

Expected effects (community)

In diabetics: stable glycemia; in longevity circles: mild metabolic effects, but some avoid it due to possibly blunted training adaptations.

Protocol — official vs community

Official / label

T2D: 500–2,550 mg/day divided; XR formulations preferred for GI tolerance. Off-label longevity/Prediabetes use mirrors T2D dosing.

  1. 01Start 500 mg with the evening meal
  2. 02Add 500 mg steps weekly as tolerated

Duration: Chronic.

AMPK activation, hepatic glucose output suppression. B12 monitoring with chronic use.

Community (anecdotal)

500–1,000 mg/day (often 500 mg with the largest meal).

Cycle:
Continuous.
Break:
None; hold around intense exercise blocks — the exercise+metformin AMPK-blunting debate is unresolved.

Cheap, prescription-accessible, real human data — the unglamorous backbone of longevity stacks.

Human evidence

Approved for T2D for decades; MILES pilot (2019) and small RCTs with mixed signals; TAME ongoing.

Preclinical evidence

The preclinical phase was completed and submitted to regulators as part of registration; pharmacology and toxicology details are part of the official label.

Known risks

  • GI adverse effects (diarrhea, nausea) — most common reason for stoppingcharacterized
  • Lactic acidosis (rare but serious)characterized
  • Reduced B12 absorption with long usecharacterized

Teal: characterized in clinical/labeling contexts. Amber: theoretical or reported outside controlled settings.

Unknowns & evidence gaps

  • Whether it slows aging in people without diabetes
  • Interaction with exercise (some data suggest it blunts exercise muscle gains)

Frequently asked questions

References

  1. Barzilai N. et al., MILES pilot study (Aging Cell, 2019)
  2. TAME trial — design and progress (Barzilai, 2016+)