What's the difference between Metformin and Rapamycin?
Metformin is a metabolic that metformin's molecular mechanism of action has been progressively elucidated over decades and now involves multiple overlapping pathways, though which pathway dominates in any given…. Rapamycin is a longevity that rapamycin's mechanism of action centers on its inhibition of the mechanistic target of rapamycin (mtor), a central serine-threonine kinase that integrates nutrient, growth factor,…. The two differ in mechanism, half-life (not reported vs not reported), and typical dose range.
Which has the longer half-life, Metformin or Rapamycin?
Metformin has a half-life of not reported. Rapamycin has a half-life of not reported. Longer half-lives generally mean less frequent dosing but slower on/off kinetics.
Can you stack Metformin and Rapamycin?
Stacking depends on mechanism overlap, safety profile, and goals. Metformin and Rapamycin should only be stacked after reviewing each compound's individual protocol page, side effect profile, and any published interaction data. Use the BodyHackGuide stack builder for a structured review before combining research compounds.
Is rapamycin actually proven to extend lifespan in humans?
Not yet. The mouse data is the strongest in geroscience — +9-26% median lifespan across NIA ITP studies, replicable across labs. But the only formal human RCT (PEARL, 2023, 130 adults, 1 year) measured safety + biomarkers + physical performance, not lifespan. A formal human lifespan trial would need decades + thousands of participants and doesn't currently exist. Geroscience consensus: mouse data is suggestive but not proof.
Can I take metformin and rapamycin together?
Yes — this is the most common longevity stack (Attia, Sinclair, Kaeberlein protocols). Metformin daily 500-1000 mg + rapamycin 5-6 mg once weekly. They hit different points in the same pathway (AMPK + mTORC1) and have additive autophagy effects. No major drug-drug interaction concerns. Get quarterly labs while stacking: CBC, lipid panel, fasting glucose, creatinine, B12.
Why is rapamycin dosed once weekly for longevity but daily for transplants?
Daily rapamycin inhibits BOTH mTORC1 (the longevity-relevant target) and mTORC2 (which controls insulin signaling + glucose metabolism). Chronic mTORC2 inhibition is what drives the metabolic side effects in transplant patients (hyperglycemia, lipid elevation). Weekly pulse dosing — 5-6 mg every 7 days — inhibits mTORC1 enough to trigger autophagy benefits while letting mTORC2 recover between doses. PEARL trial data supports this approach as safe over 1 year.
What's the deal with metformin blunting exercise adaptations?
A 2019 study (Konopka et al., Aging Cell) showed metformin reduced mitochondrial respiration improvements in older adults doing aerobic training. The effect is modest (~20% reduction in some adaptation markers) and may not apply to younger users or strength training. Practical workaround for longevity users who train hard: take metformin on non-training days, or split the dose so the post-workout window is metformin-free. Other longevity drugs (rapamycin, NMN) don't show this exercise-blunting effect.
Does rapamycin suppress the immune system?
At immunosuppression doses (2-5 mg/day) — yes, that's the indication. At weekly longevity doses (5-6 mg once/week) — minimally per PEARL trial. Some users report slight increase in mouth sores or mild fatigue around dose day. If you're getting frequent infections or wound healing slows visibly, that's a signal to drop the dose or pause. People on chemotherapy, recent surgery, or with chronic infections shouldn't be on longevity-dose rapamycin without physician oversight.
Is berberine a real metformin substitute?
Partially. Berberine also activates AMPK and improves insulin sensitivity, but at ~1/3 the potency of metformin per gram. Typical dose: 500 mg 2-3×/day. Pros: no prescription needed, fewer GI side effects long-term. Cons: weaker glucose-lowering effect (HbA1c reduction ~0.5% vs metformin's ~1.5%), lacks the 60-year safety database. Reasonable choice for users who can't tolerate metformin or want an OTC option, but for confirmed prediabetes or T2D, metformin remains the higher-evidence pick.
