Metformin vs Rapamycin
Which longevity drug has the better evidence?
Last updated: 2024-12-06
Metformin
AMPK activator. FDA-approved for diabetes. The "safe, cheap, and well-studied" option with promising but unproven longevity benefits in non-diabetics.
Rapamycin
mTOR inhibitor. FDA-approved as immunosuppressant. The strongest lifespan extension data in mammals, but more risks and unknowns in humans.
Side-by-Side Comparison
Extends lifespan in some mouse strains by ~5% at best. Higher doses shortened lifespan. A 2025 meta-analysis found no reliable lifespan extension in vertebrates.
Extends lifespan 9-26% in mice across multiple labs and strains. A 2025 meta-analysis confirmed rapamycin mirrors dietary restriction effects on lifespan. The most robust data of any drug.
Diabetics on metformin live longer than non-diabetics in some studies—intriguing but not causal proof. TAME trial would provide answers but remains underfunded.
PEARL trial (2025) showed safety over 48 weeks. Some muscle mass gains in women. No human lifespan data yet. More experimental than metformin.
Activates the cellular energy sensor AMPK, which indirectly inhibits mTOR. Also reduces inflammation and improves insulin sensitivity.
Directly blocks mTORC1, the master growth regulator. More potent mTOR inhibition than metformin. Strongly activates autophagy.
Diabetics on 5+ years of metformin were ~3 years younger by Horvath clock. An RCT showed 1.8-3.5 year reductions in biological age markers.
Some studies show slowing, others neutral or even acceleration. A 2024 D+Q study found similar inconsistency. Clock effects unclear.
Used by 120+ million people. Main issues: GI upset (common), B12 deficiency (monitor), rare lactic acidosis (kidney/liver disease). Very well understood.
Immunosuppression risk even at low doses. Can impair wound healing, elevate glucose/lipids. Long-term low-dose safety unknown. Bryan Johnson quit citing side effects.
Generic, extremely affordable. Often $4 at major pharmacies. Cost is essentially a non-issue.
Brand-name (Rapamune) expensive. Compounded versions cheaper but have lower/variable bioavailability. Still much more expensive than metformin.
Any doctor can prescribe. Some telehealth services prescribe for longevity purposes. Very low barrier to access.
Requires a physician willing to prescribe off-label. Longevity clinics offer it but at premium cost. More friction than metformin.
500-1500mg daily with food. Extended-release preferred. Some cycle it around exercise. Straightforward.
3-10mg once weekly. Blood level testing recommended due to high individual variability. More complex protocol requiring medical oversight.
Some studies show reduced muscle protein synthesis and VO2max adaptations. Many users skip metformin on training days.
mTOR is needed for muscle growth, raising concerns. But PEARL trial showed muscle gains in women. Effects may depend on timing and dose.
Peter Attia categorizes metformin as "fuzzy"—mechanism is sound but human longevity evidence is circumstantial. Many longevity experts take it anyway.
Attia calls rapamycin "promising" based on animal data. The ITP confirmed its lifespan benefits. But human translation remains unproven.
This is genuinely a hard choice, and honest experts disagree.
**Rapamycin has better animal data.** A 2025 meta-analysis across 167 vertebrate studies found rapamycin reliably extends lifespan like dietary restriction does—metformin did not. If you're betting on which molecule actually slows aging at a fundamental level, rapamycin has the stronger mechanistic case.
**Metformin has the better safety profile.** 60+ years of use in millions of people. We know what it does and doesn't do. The risks are well-characterized and manageable. For something you might take for decades, this matters.
**Neither has proven human longevity benefits.** This is the uncomfortable truth. The TAME trial for metformin and larger rapamycin trials would answer this—but they're either underfunded or just beginning. Anyone taking either drug for longevity is making a bet based on incomplete evidence.
**Cost and access favor metformin dramatically.** At $4-15/month vs $50-200+/month, metformin is 10-50x cheaper. It's also much easier to get prescribed.
Some longevity researchers take both, reasoning they work through complementary pathways (AMPK vs mTOR). Studies suggest the combination may have synergistic anti-aging effects. But this adds complexity and cost.
Which Is Right for You?
- You want the safest, most well-studied option
- Cost is a significant factor ($4-15/month vs $50-200+)
- You prefer something any doctor will prescribe
- You're pre-diabetic or have metabolic syndrome (proven benefits)
- You want to start with the "entry-level" longevity intervention
- You're not comfortable with immunosuppression risks
- Animal lifespan data is most important to you
- You're comfortable with more unknowns and closer medical monitoring
- You have access to a longevity-focused physician
- Cost is not a barrier
- You haven't seen benefits from metformin alone
- You're particularly interested in autophagy activation
Important Note
This comparison is for educational purposes only and should not replace medical advice. The best medication for you depends on your individual health profile, medical history, and personal circumstances. Always consult with a healthcare provider who can evaluate your specific situation before starting any medication.