Metformin is a biguanide drug that primarily activates AMP-activated protein kinase (AMPK), a master metabolic regulator. This action mimics a state of caloric restriction, leading to improved insulin sensitivity, reduced hepatic glucose production, and modulation of cellular pathways related to aging, such as inflammation and autophagy.
Verdict
A promising metabolic modulator for healthspan, but evidence in non-diabetics is evolving.
HEALTHSPAN IMPACT
Moderate
RISK LEVEL
Moderate
EVIDENCE GRADE
B
MONTHLY COST
$4 - $20
Protocol
- Off-label healthspan protocols often involve 500mg to 1500mg daily, typically with the largest meal.
- Some protocols suggest cycling or skipping doses on exercise days to avoid blunting training adaptations.
Flags
- Common side effects include gastrointestinal issues like diarrhea, nausea, and gas.
- Carries a black box warning for lactic acidosis, a rare but serious complication.
- May interfere with the absorption of vitamin B12, requiring monitoring and supplementation.
- May blunt the hypertrophic and mitochondrial adaptations to strenuous exercise.
- Contraindicated in patients with severe renal impairment or certain liver conditions.