Metformin
Metformin (Glucophage)
The most prescribed diabetes drug in the world, now being studied as the first pharmaceutical designed to target aging itself — the TAME trial.
Metformin is FDA-approved for the management of type 2 diabetes. Off-label use for longevity or other purposes beyond its approved indication is not FDA-approved. This page discusses the compound in a research context. Any use should be supervised by a qualified healthcare provider.
What it is
Metformin is a biguanide compound derived from guanidine, found in French lilac (Galega officinalis). It has been used for type 2 diabetes since the 1950s and is the most prescribed diabetes medication worldwide. Its safety profile is extremely well-characterized over 70+ years of use.
In longevity contexts, metformin has gained attention for its apparent effects beyond glucose control: AMPK activation, mTOR inhibition, reduced inflammation, and epidemiological data showing that diabetics on metformin outlive non-diabetics not taking it. The TAME trial (Targeting Aging with Metformin), led by Nir Barzilai, is the first FDA-authorized clinical trial explicitly designed to test whether a drug can treat aging as a disease — a landmark moment in the field.
What research shows
- AMPK activation — improves insulin sensitivity and reduces hepatic glucose output
- mTOR pathway inhibition — overlapping longevity mechanism with rapamycin
- Epidemiological data: diabetics on metformin have lower all-cause mortality and cancer rates than non-diabetics not on metformin
- Reduced cardiovascular mortality in large observational studies
- Anti-inflammatory effects — reduced IL-6 and CRP in some studies
- TAME trial ongoing — results will be a landmark in longevity medicine regardless of outcome
What remains unknown
- Whether longevity benefits extend to non-diabetic, healthy individuals — TAME trial will address this
- Impact on exercise adaptations — Peter Attia stopped metformin citing evidence it blunts mitochondrial adaptations to exercise
- Optimal dosing for longevity vs. glucose control
- Long-term B12 depletion — metformin reduces B12 absorption; monitoring and supplementation needed with long-term use
Administration basics
Common use cases
Type 2 diabetes (approved), off-label longevity protocols, metabolic health, cancer risk reduction.
Half-life
~4–8 hours. Typically dosed twice daily with meals.
Administration
Oral tablet. Extended-release (ER) formulation reduces GI side effects. Available as cheap generic; prescription required.
Research Protocols & Common Usage
Doses used in research
- Standard diabetes dosing starts at 500mg twice daily, titrating to 1000mg twice daily
- TAME (Targeting Aging with Metformin) trial uses 1500mg/day
- Some longevity practitioners use lower doses of 500mg/day
Administration routes studied
Typical protocol duration
Diabetes treatment is long-term and ongoing. Longevity protocols are also ongoing with periodic monitoring including B12 levels.
Common stacking protocols
- Metformin + Rapamycin — combined in some longevity protocols for complementary mTOR and AMPK pathway targeting
- Note: Metformin + NMN combination is controversial — some research suggests metformin may blunt exercise-induced adaptations
Contraindications & combinations to avoid
- Renal impairment — metformin accumulates and can cause lactic acidosis; eGFR must be monitored
- Contrast dye procedures — metformin must be held 48 hours before and after contrast administration
- Heavy alcohol use — increases lactic acidosis risk
- Heart failure — associated with lactic acidosis risk
- Berberine — additive blood glucose lowering; hypoglycemia risk
- May blunt exercise adaptation — some research suggests attenuation of aerobic exercise benefits on mitochondrial biogenesis
Dosing information reflects doses used in published research and commonly reported community protocols only. This is not a personal recommendation. These compounds are not FDA-approved for human use in the contexts described. Consult a qualified healthcare provider before starting any protocol.
Considering stacking?
See the stacking guide for common combinations with Metformin and what to avoid.
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