SGLT2 inhibitors

My longevity doc has suggested canaglaflozin as another pharmaceutical showing strong signals in cardio protection, kidney protection, improved glucose and maybe even some malignancy protection. It seems to be a bit like Rapamycin, different mechanism of action, but ability to positively affect entire metabolic systems.

I’m wondering if anyone in this community has experience with this class of drug? For those unfamiliar, here is a very informative video on its overall effects. The sound gets a bit jankey, but if you bear with it there’s good information here:

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She talked about the concept of aestivation, and referenced this paper.

She also mentioned Sengupta, and said “Fasting/caloric restriction inhibit mTOR, which has been shown to prolong lifespan. Ketogenesis does the same thing. Sengupta (Nature 2010).”

I was fast forwarding and reading the slides.

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I am interested as well but I am concerned that this class of drugs increases ldl cholesterol

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I haven’t read anything about SGLT2 inhibitors increasing ldl. That doesn’t mean there is no effect, I just havent seen it mentioned in numerous papers and lectures.

Our Rapadmin has several great posts on SGLT2 Inhibitors. Just put "SGLT2 inhibitors " in the search bar and they will come up in a scroll of posts…

Hi, yes many here are taking it. See discussion threads here: Canagliflozin - Another Top Anti-aging Drug

and here Canagliflozin and Empagliflozin: Canagliflozin for Anti-aging (part 2)

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I’ve read your thread which was very interesting. You said that after a while you felt exhausted. Do you have any idea why?

If I am understanding the mechanisms of action and metabolic shifts correctly one possibly switches to more ketone production. Do you think that didnt happen for you? In that situation you could be hypoglycemic, hence feeling exhausted?

No idea why at all. It seems to be a rare side effect of the medication. I have had no issues with empagliflozin. Everyone is different. I’m sure most people don’t experience that specific side effect.

I use a CGM and track my blood glucose levels when I’m trying medications like this. No issues there - as far as I can tell.

Where are you all getting your SGLT2 inhibitors? I’m aware of several sources online but have concerns about consuming gray market pills (in addition to rapa) which may have adulterants. If you’ve managed to get these prescribed, how? If you are taking gray-market: do you have concerns about impurities? The fact that nitrosamines have been found even in product intended for the United States is quite concerning.

I have a longevity doctor (I live in the US). He prescribes these and other pharma for me based on his evaluation of my health and optimization needs.

Look on our list of reliable online pharmacies. Most of them sell rapamycin and sglt2 inhibitors like canagliflozin and empagliflozin. Cost is about $60/month for 30 pills.

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I get Farxiga (dapagliflozin) through insurance really cheap with the copay assistance card. I don’t have great insurance (BCBS HMO from the healthcare.gov marketplace). Have you guys tried requesting it from your doc? I think that the cardioprotection benefit is understood by cardiologists now and they should prescribe it for that reason alone (provided you have such risk). Incidentally, I also get Ozempic really cheap this way. No prior auth was required. Cardiologist sent script and pharmacy filled it with no insurance drama.

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Did you start at 10mg and work your way up to 25 mg?

I did. Went for a week or two at 10mg, then bumped it up. No issues with this approach.

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Anyone taking an SGLT2 inhibitor and Acarbose together concurrently?

The ITP study shows canagliflozin intake provides no benefit (for mice), whether for median lifespan, or maximal lifespan.

Sorry. That was for female mice. Scrolling down, there is benefit for male mice, both in terms of median lifespan and maximal lifespan.

An interesting bit of news on SGLT2 inhibitors - seems like the increase in beta-hydroxybuterate concentration would be a good thing if not excessive:

Ketogenic diets (KD), alternate-day fasting (ADF), time-restricted feeding (TRF), fasting, diabetic ketoacidosis (DKA), and SGLT-2 inhibitors cause an increase in BHB concentration.

β-Hydroxybutyrate as an epigenetic modifier: Underlying mechanisms & implications

Ketone bodies & BHB not only serve as ancillary fuel substituting for glucose but also induce anti-oxidative, anti-inflammatory & cardioprotective features.

β-Hydroxybutyrate as an epigenetic modifier: Underlying mechanisms and implications

https://www.sciencedirect.com/science/article/pii/S2405844023083068

https://x.com/AZMD_1/status/1714726667162140981?s=20

Source posts:

https://x.com/heniek_htw/status/1766537499898245517?s=20

Related:

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Did you get any additional weight loss from empagliflozin after switching?

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No, no added weight loss after switching to Empa.

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From NIA ITP: longevity benefits are seen for Canagliflozin only for male mice, also according to Richard A Miller, in old female mice, Canagliflozin levels are 10x higher than in younger males - from research on mice we could assume that older people could need lower dose and that women could need lower dose - but it is tested now in mice (there are 2 new studies in progress to test this in mice):

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I’ve added HMB power to my protein shake. Data on its usefulness in MPS is mixed, but I figured it couldn’t hurt