Does rapamycin + canagliflozin (or other SGLT2's) synergize well beyond just rapamycin + metformin?

Has anyone done studies in this? I think there’s strong case they could.

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That is a good question Alex. We have a little information, but I don’t think we have as much as we’d like in the way of good studies in this area.

We have some data around the issue of avoiding side effects of the glucose management medication, and things to avoid if you are exercising and want to maintain muscle strength and/or growth.

We know that Metformin has some significant impact on muscle recovery:

And we have a little bit of data on Canagliflozin in the area of muscle recovery in mice (but much less data than with metformin):

On the benefits / synergies side, we have some synergistic data but some of its in models that are not seemly close to healthy human applications:

I don’t think there is enough information yet to draw any conclusions on comparative synergies.

I go with pulsed SGLT2 inhibitors just because it seems there is less risk than with metformin for muscle issues, but thats due to my own personal priorities. Your assessment may differ.


SGLT2.pdf (1.5 MB)


. Empagliflozin was best.

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For a non T2D patient, do we know the optimal dosage for life extension for empagliflozin? 10 mg daily or 12.5 mg? (25 mg split in half which also cuts the cost in half) @adssx

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And for people considering an SGLT2 inhibitor medication like canagliflozin or empagliflozin, the price for the larger, higher dose tablets is not much higher than the lower dose tablets, so there is a great opportunity to save money by pill splitting with these drugs if you only want to take the lower dose:

Its fine to pill-split these drugs. And you’ll save perhaps 30% to 50% of the monthly cost.


We don’t know. We don’t even know if empagliflozin extends lifespan :wink: (And we don’t know if empagliflozin is best.)


I’m going to gamble that it does. Probably dapagliflozin would work as well. I think I’ll try 12.5 mg of empagliflozin. I’ll split a 25 mg pill in half as well as the cost.

The kicker for me was the anti-cancer properties especially effective Vs prostate cancer.


It’s also my gamble :slight_smile: I’m using 10 mg dapagliflozin. I think dapagliflozin and empagliflozin are as good: Comparison of Effectiveness Among Different Sodium‐Glucose Cotransoporter‐2 Inhibitors According to Underlying Conditions: A Network Meta‐Analysis of Randomized Controlled Trials 2024


Read my second post comparing SGLT2 inhibitors and doses.

Read my second post comparing SGLT2 inhibitors and doses. Epagliflozin 25 mg. got best results

I saw it, but it’s garbage from 2022 published by “researchers” from “The Second Affiliated Hospital of Nanchang University” published in Frontiers (predatory & low quality). I posted a 2024 review by Mount Sinai + University of Tokyo + Johns Hopkins + London School of Hygiene + Albert Einstein College of Medicine + UCLA researchers published in the Journal of the American Heart Association. It trumps all previously published garbage. [Also, the review you posted is about T2D only, whereas the 2024 one covers all underlying conditions: T2D, HF, and CKD, so more likely to be generalized to the healthy population.]

Other than Ertugliflozin, which seems to be the most ineffective one, it doesn’t look like the hazard ratios of the rest are too much different. Maybe I am interpreting the charts wrong.

I prefer Canagliflozin because I just need to take it once daily in the morning,

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That’s the whole point of the article: in terms of effectiveness, they’re all almost identical. In terms of side effects, there are major differences though, see Supplemental Figures:

Canagliflozin is the only SGLTi associated with a significant risk in amputations and fractures:

Canagliflozin is very close to have a significant risk for DKA as well:

Empagliflozin has the lowest genital infection risk:

But empagliflozin causes way more orthostatic hypotension than dapagliflozin:

So canagliflozin is the worst in terms of safety profile.

You can do the exact same thing with dapagliflozin and empagliflozin. You can take dapagliflozin and empagliflozin whenever you want whereas canagliflozin must be taken before the first meal of the day.

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“The prescribing information for canagliflozin lists lower limb amputation as an uncommon side effect, occurring in between 1 and 10 patients in 1,000.”

From my readings, it’s mainly in patients with pre-existing diabetes and/or with pre-existing diabetic foot disorders.

“Amputations of the toe and middle of the foot were the most common; however, amputations involving the leg, below and above the knee, also occurred.”