Metformin
Half-life
~4-6 hours
What is Metformin?
First-line diabetes medication and longevity drug. Activates AMPK, reduces hepatic glucose output.
How Metformin works
Activates AMPK and suppresses hepatic gluconeogenesis, improving insulin sensitivity and metabolic control.
Benefits & uses
Common uses: Blood glucose control, insulin sensitivity, longevity (rapamycin alternative), PCOS.
Metformin dosage
Protokol doesn't recommend doses for prescription or controlled compounds. Any figures below are reference or observational reports — dosing should be set with a qualified clinician.
- Reference range
- Prescription-dependent (commonly 500–2000 mg/day); doctor-directedClinical or reference range, not a personal recommendation.
Metformin half-life
~4-6 hours
Metformin side effects
GI upset (significant initially), B12 depletion, lactic acidosis risk (rare).
- GI upset/diarrhea
- B12 depletion long-term
- Lactic acidosis risk in severe renal failure
- GI upset (diarrhea, nausea) — common early
- Reduced B12 absorption over time
- Rare lactic acidosis
Warnings & monitoring
- Prescription medication — requires a doctor. Long-term use can lower B12 (monitor). Not for significant kidney impairment.
Metformin interactions
with Berberine
Caution · moderateBoth berberine and metformin activate AMPK and lower blood glucose through similar mechanisms. Additive hypoglycemic effect can cause dangerous blood sugar drops, especially in fasted states or with exercise.
Timing: Use half-doses of each if combining; monitor blood glucose closely
with Berberine
Caution · moderateBoth berberine and metformin activate AMPK and lower blood glucose. Combining them may cause hypoglycemia. If switching from metformin to berberine, do not use both simultaneously.
Timing: Do not combine without monitoring — additive glucose-lowering effects
with Berberine
Caution · mildBoth lower blood glucose via AMPK activation; stacking risks hypoglycemia and additive GI side effects. Watch fasting glucose closely.
Timing: Separate by 2+ hours; halve doses initially
with MK-677
Caution · moderateMK-677 increases GH and can raise fasting glucose/insulin resistance. Metformin mitigates this effect and is sometimes co-prescribed. Monitor HbA1c and fasting glucose.
Timing: Metformin taken with meals; monitor fasting glucose closely
with NAD+
Caution · lowResearch (Barzilai et al.) suggests metformin may interfere with exercise-induced mitochondrial biogenesis associated with NAD+ precursors. Consider cycling metformin or timing apart from exercise.
Timing: Metformin may blunt exercise-adaptation benefits of NAD+ precursors
with NMN
Caution · lowDavid Sinclair's research indicates metformin may interfere with exercise-induced longevity benefits of NAD+ precursors like NMN. Consider separating use or cycling metformin.
Timing: Evidence suggests metformin may blunt NMN's exercise performance benefits
Track Metformin in Protokol.
Log doses, model half-lives, check interactions, and line it all up against your bloodwork. Free on iPhone and Android.
