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Rapamycin and metformin together, anyone actually running both?

Posted by wes149 in Longevity & Anti-Aging - 4 points, 6 comments.

I have been digging into the longevity stuff for a while now and one thing keeps coming up in my reading, the combo of low dose rapamycin with metformin. Both seem to hit different longevity pathways, rapamycin through mTOR inhibition and autophagy, metformin through AMPK. On paper it seems like they should complement each other pretty well.

But I am curious if anyone here is actually running both and what your reasoning was for stacking them instead of picking one. My main concerns are the side effect overlap, especially GI stuff and the lipid changes rapamycin can cause. I have also seen people mention timing them apart to reduce that.

I have not pulled the trigger on either yet, still doing my homework and getting bloodwork first. My doc is open to talking about it but I want to go in with a real plan instead of just guessing.

For those of you with experience, what did your weekly and daily layout actually look like, and did you notice anything tangible in recovery, energy, or sleep after a few months...

Comments

  • tyler_m: Honestly the "stack everything for longevity" crowd always makes me a bit twitchy, because you're layering side effects on top of each other without knowing which one is actually doing what. MTOR inhibition and AMPK activation do different things sure, but to be fair you dont really know if hitting both at once is additive or if one is just redundant given the other. What did your bloodwork look like before you started looking at this? And have you actually found a human trial testing the combo
  • ethan405: Yeah this is exactly where my head goes too leh. Fwiw I looked for actual human combo trials a while back and couldnt find much beyond the separate mechanistic stuff. Most of the "synergy" talk seems to be people connecting dots from two different study populations and assuming it carries over. That overlap on GI side effects alone would make me want to see combo data before jumping in. Are you running either one on its own right now?
  • aspiring_grinder: That additive vs redundant point is the actual question, isn't it. I tried stacking them for about six weeks and honestly couldn't tell what was doing what, lipids drifted up a bit and gi was annoying enough that i dropped the rapamycin and kept just the metformin. Bloodwork before was fine, normal lipids, a1c on the higher side of normal which is why metformin interested me in the first place. And yeah, no combo trial i could find, everything is extrapolated from separate data. That's kind of
  • wes149: Yeah six weeks is a pretty fair trial, not like you quit early on that. The lipid drift is exactly what has me hesitant on the rapamycin side specifically. When you dropped it and went metformin-only, did your lipids bounce back or did you have to address them separate from that? And was the metformin GI stuff still there for you or did that settle down once you were down to just one? I keep reading about timing tricks like taking them a few days apart but sounds like that is pretty individual
  • wes149: Yeah still in research mode, not running either one yet. Bloodwork first like I said. Your point about combo trial data is a good one, imo that is exactly the gap I keep running into. Everyone cites the separate mechanisms but I have not found a lot of actual human data on running them together long term. Makes me think I should start with just metformin since it has a longer safety track record in non-diabetics and see how I tolerate it before adding rapamycin on top. That pacing feel reasonab
  • wes149: Fair point about the additive vs redundant question, imo that is exactly the kind of thing I am trying to figure out before I spend money on this. To answer your questions, my baseline bloodwork was pretty standard stuff, metabolic panel and lipids. Nothing alarming but I want a fuller picture before even thinking about dosing. And no, I have not found direct human trials on the combo itself, most of the enthusiasm does seem to be extrapolated from separate studies. That is part of why I posted

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