In most cases, it is safe to take these medications simultaneously. Metformin and Rapamycin have synergistic benefits. Rapamycin inhibits mTOR to target cellular senescence, while Metformin’s primary benefit is optimizing metabolic health. Metformin’s benefits as a fasting mimetic also increases mTOR inhibition, which thereby increases autophagy and reduces the harm of senescent cells.
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Safe, but metformin itself is probably not very useful. It’s good at lowering glucose, but there are better drugs for that.
Hey Paul, we’re actually moving to push patients to acarbose. It’s not that there is not a lot of observational data on metformin, but some of the evidence from NIA ITP has caused us to take a deeper look at acarbose.
Here’s an outline of some of the reasons that acarbose should be considered in a longevity protocol:
We’ve been interested in some of the complimentary benefits of gut microbiota remodeling and the downstream benefits of reducing systemic inflammation. Acarbose is likely to affect lifespan through pathways at least partly distinct from mTOR signaling. It was proposed that the combination of rapamycin and acarbose might have additive effects on lifespan through their complementary mechanisms of action.
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Fantastic!!! Thanks for the reply, Daniel, and for the great link.
Hi Daniel,
I agree that there is little evidence to support Metformin as an anti-aging factor (specific). However, Rapa/Met combinations seem to ameliorate the hyperglycemic (among other detrimental metabolic) negative effects of rapa usage (only), without effect on the benefits. The inclusion of Met seems to have a beneficial metabolic buffering effect that I think most users would want to consider.
This is definitely where testing comes into play. If we can avoid concurrent use, it would be preferable to. Our concern would be inhibiting mTOR too much. However, there is a very valid reason for using metformin to address hyperglycemia writ large. We can look at a patient’s lab work to see if it is necessary to add metformin to their protocol.
Let me know if that reasoning makes sense or if there’s anything you’d like clinical or research review team to address.
Daniel,
I would love to see some research on the effect of increased cAMP (via Forskolin/Butyrate) activation on mTOR activation (specifically MTORC1) in the presence of Rapa/Met combinations (both through what channels and where - up/down stream). I wonder if the potential anti-bacterial effects of upregulating HDP’s would help mediate the immunosuppressive aspects of Rapa.
Thanks! Interesting. I see the source there, for both excerpts, is the Fight Aging! blog. “Reason” is the name of the person who runs that blog, and “Reason” makes, or hopes to make, money by his own admission elsewhere in the blog, that he invests in start-ups researching new longevity drugs. So if he might make $ when new research into new drugs is funded, then he would be profit-motivated to poo-poo other generic drug interventions that are already in existence, yes?, in order to keep up the interest of private equity in investing in the projects where he invests also, am I thinking about that wrong? Just trying to understand it all, I’m new at this. Thanks.
Ive been on Metformin for about 6 years for weight loss and anti aging, but Now that I recently started Rapamycin and Acarbose, I wonder if still taking Metformin with the other two is useful at all in reducing your risk of some diseases, like atherosclerosis CVD and cancer for instance? Or do you think Rapamycin plus Acarbose is enough to help protect against atherosclerosis CVD? I also have to take a Statin(Rosuvastatin) for high LDL, that Ive had since ny early twenties no matter how healthy I was. I know Rapamycin has cardiovascular protective effects and so does Acarbose. Any thoughts on this?