Rapamycin and metformin together, anyone running both?

Posted by humblequinn in Longevity & Anti-Aging - 4 points, 6 comments.

I've been reading up on rapamycin (the /peptides/rapamycin profile here is a good summary) and I keep seeing metformin mentioned alongside it in longevity protocols. Both seem to mimic caloric restriction but through different pathways, rapamycin hitting mTOR and metformin working through AMPK. On paper that sounds complementary, but I've got no idea whether it actually plays out that way in practice.

I'm keen to hear from anyone who's tried both together. Did you notice anything different compared to just one or the other? Any issues with side effects stacking up, like GI upset from both at once? I'd reckon the lipid changes from rapamycin plus the B12 depletion risk from metformin would be worth watching with bloodwork, but I'm honestly just guessing at this stage.

Also curious about timing. If rapamycin is typically once weekly and metformin is daily, do people just run them on their own schedules and let them overlap naturally, or do you space the metformin dose away from the rapamycin day? Seems like there'd be a fair bit of individual variation in how people approach this.

Still pretty new to all this so any real-world experience would be heaps appreciated. I'm not on either yet, just trying to get my head around the landscape before I give it a crack.

Comments

• sleep_coastal: Anecdotally I tried this combo for about 4 months. Ran rapamycin once weekly, metformin daily, just let them overlap naturally. The GI thing is real though. Both hit your gut differently but the combined effect was rougher than either alone, especially rapamycin day. I ended up skipping metformin the evening before and morning of rapamycin day and that helped a lot. B12 is worth checking, mine dipped after maybe 10 weeks. Lipids didn't move much for me but I've heard others say different. Hone
• raj_j: The B12 dip makes sense, metformin's known for that over time. I'd been messing with B12 shots for focus stuff recently and noticed a difference pretty quick, might be worth checking yours before you start the combo not just partway through. The flat energy on training days is what would worry me more honestly. Did you play with timing at all, like moving rapamycin further from your harder sessions?
• humblequinn: Good call on checking B12 before starting, not just midway through. I haven't actually begun the combo yet, still gathering info, so getting a baseline now makes a lot of sense. I'll add it to my next bloods. On the training timing question, I haven't started yet so no personal experience there, but that's exactly the kind of thing I'm keen to hear about. Do you space your rapamycin dose a couple days out from heavy sessions, or is it more about just avoiding the same day?
• humblequinn: Good on ya for sharing that, really useful detail. The GI stacking is exactly what I was worried about. Skipping metformin around rapamycin day sounds like a smart workaround, did you just drop the evening before and morning of, or the full day after as well? The flat energy on training days is interesting too, that's the kind of thing I'd hate to discover after committing to the combo.
• nomad_renee: The full day after as well is what I'd do, anecdotally metformin GI can lag by a day so just skipping morning of might not be enough lah. The flat energy thing is real though, I noticed it more with metformin than rapamycin, rapamycin day itself I feel fine but the day after is a bit meh. Tracking HRV helped me see the pattern, might be worth doing if you're testing the combo.
• humblequinn: Cheers for that, the lagged GI thing is exactly the kind of detail I was missing. I'd have just skipped the morning dose and thought that'd cover it. The flat energy on metformin versus the meh day after rapamycin is a useful distinction too, sounds like they could stack into a proper slog if timed wrong. Reckon I'll give HRV tracking a crack since you found a pattern there. Did you see the energy dip settle after a few weeks or did it stay consistent?

Community discussion - research and educational context only. Not medical advice.