Rapamycin and Metformin Show Synergy in Mice

These are mice that are predisposed to diabetes, but considering how prevalent diabetes is in humans, it seems relevant.


Now that I am taking Rapamycin, I have switched back to daily Metformin and am considering raising the dosage to 1 g daily. I will keep my eyes open for hypoglycemia effects although I think I am now tilted towards hyperglycaemia.

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My feeling is Z2 training should be the first line treatment for diabetes, not metformin (especially since the latter inhibits adaptation from exercise).

High intensity is probably better since that clears muscle glycogen making the muscle again insulin sensitive

Can’t (shouldn’t) do HIT daily though…

2 times per week is enough to have empty glycogen stores for most of the time

No, glycogen will be replenished quickly (assuming you eat carbs)…

Zone 2 does deplete glycogen but requires longer durations… That said glycogen depletion isn’t the primary mechanism through which it improves blood sugar control.

Iirc even on a high carb diet it takes around 24-48h to completely replenish them (actually on a low carb diet after adaptation glycogen replenishment is as fast as on a high carb diet according to muscle biopsy studies done by Volek )

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[quote=“Maveric78, post:3, topic:2807”]
metformin (especially since the latter inhibits adaptation from exercise).
[/quote]metformin (especially since the latter inhibits adaptation from exercise).
I have been taking metformin for 25+ years. I am not a “bodybuilder”, but I have certainly been able to gain muscle mass. Maybe it takes a little longer, but it certainly does not prevent muscle gain. Do you think metformin prevents muscle gain? I don’t think so.
Do you think metformin prevents the maximum muscle mass you can gain or will it just take a little longer?

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Yes, the research suggests that adaptation to both strength and endurance exercise will be inhibited. You can certainly still improve but your ceiling will be lower.

So, you have to ask yourself: Do I want more muscle mass (probably more than you need and probably just for vanity’s sake ), or do I want to live longer?


I’m sorry but I think all this hysteria about Metformin inhibiting strength and hypertrophy is completely overblown. I don’t remember the specifics of the one or two studies on this but it was a minute percentage. Anecdotally, I’m 66 and have lifted most of my life. I have gone on and off Metformin over the years and have noticed zero difference in these two metrics. I’m currently on it and am stronger and have as much muscle mass now as ever in my life. There is a recent study about Metformin and V02 max which is a bit more concerning from a longevity standpoint but there too, it doesn’t seem to have a significant effect and we certainly need to wait for more evidence (TAME study).


As we age our ceiling for muscle size, strength and endurance is continually dropping… why lower it further with metformin? Remember both VO2 and muscle strength have strong correlations with longevity.

Anecdotes :roll_eyes:


Show me your data that rapamycin causes or increases muscle loss.
I take metformin. I have never done TRT.
I have always exercised moderately.
I prefer to be light and flexible.
I posted this picture earlier but I will post it again.
This is me at 81+ years. I will post a new one year after this one.


You reply to a criticism of anecdote with another anecdote??

Your opinion is so utterly entrenched that I know this will be wasted, but here is some DATA:

I agree.
I’m 65 and still run and go to the gym.
Last year I achieved one goal; I did a one-armed chin-up. (OK; it wasn’t the cleanest, neatest version ever done but I was happy with it!) And I’ve been on metformin for 12 years.
I concur with the “hysteria” label.

If VO2 and muscle strength were correlated with longevity, then shouldn’t we see Olympic athletes regularly clocking up 100 years?
To my knowledge, only 1 Olympic athlete has made it to 100.

Anecdote. Show me the data!

Critical flaw in your argument, just because you’re an elite athlete at 25 doesn’t mean you’ll continue to train aggressively when your 60 or 70.

Eddie Merckx - the greatest cyclist in history

But here’s some DATA:

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