Canagliflozin - Another Top Anti-aging Drug

Review Paper (open access):

GLP-1 RAs and SGLT2i: two antidiabetic agents may facilitate healthy aging through the common AMPK pathway

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Thx. I’m worried that GLP-1 might be pro health in some (obese or diabetes), but not pro longevity (at least in lean, great glucose control).

SGLT inhibitors looking better and better as data comes out.

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+1

Open questions:

  1. Are all SGLT2 inhibitors equal? Are some better for some outcomes? What about SGLT1 (sotagliflozin)?
  2. What’s the optimal dose? Can we increase the dose? For instance here they reversed Parkinson’s symptoms with 20 mg/kg/day of empagliflozin (vs human DDD: 17.5 mg/day).
  3. As SGLTi bind to mTOR, should they be cycled like rapa?
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Is there any new data out that shows that SGLT2 inhibitors extend the lifespan of females? I feel like I may have missed something.

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No, but I seem to remember Richard Miller saying on one of the many podcasts I’ve listened to, that it may just be a dosing issue. They just don’t know. They only tried a single dose level.

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Makes sense because the real life benefits (diabetes, CKD, HF, dementia, etc.) don’t seem to be gender dependent.

Also just published (and does not mention gender differences): Effects of SGLT2 Inhibition via Empagliflozin on Cognitive and Physical Impairment in Frail Diabetic Elders with Chronic Kidney Disease

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We observed a favorable effect on both cognitive and physical function. Salutary vascular actions have been proposed for SGLT2-inhibitors, and we have previously observed beneficial effects on physical and cognitive function in hypertensive patients, by improving endothelial dysfunction and reducing mitochondrial oxidative stress. To the best of our knowledge, we are the first group exploring the effects of empagliflozin on cognitive and physical impairment in frail older adults with diabetes and CKD, supporting the view that SGLT2-inhibitors may be considered anti-frailty drugs.

Quite impressive after 6 months only. And on the lowest empagliflozin dose (10 mg/day instead of 25 mg/day).

I guess that’s why the ITP is now testing a smaller dose (60 ppm VS 180 ppm before).

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Another string to SGLTi’s bow?

In vivo, dapagliflozin exerts antiarrhythmic effects, revealing a potential new additional role of SGLT2 inhibitors in the treatment of atrial arrhythmias.

(Acute antiarrhythmic effects of SGLT2 inhibitors–dapagliflozin lowers the excitability of atrial cardiomyocytes 2024)

See also from Dec 2023: Sodium-glucose cotransporter-2 inhibitors had a significant association with less atrial fibrillation

There are four trials and studies of SGLT2 inhibitors for atrial fibrillation:

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Just reading some old postings in here about SGLT2 inhibitors and wanted to incorporate/start a small dose of one of them. I googled and ran into this, that says it may increase the risk of Thyroid cancer. wonder what you think about it? Or am I reading it wrong?

RYBELSUS® vs Other Diabetes Pills | RYBELSUS® (semaglutide) tablets 7 mg or 14 mg

This link seems to be about semaglutide, not empagliflozin.

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aren’t they both SGLT2 inhibitors?

No. Semaglutide is a glp1agonist. See here Intermittent (oral) Rybelsus / Semaglutide use in healthy individuals?

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No, SGLT2 inhibitors have names ending in - gliflozin (hence their other names: “flozins” or “gliflozins”). Semaglutide a GLP-1 receptor agonist, with a name ending in -tide like other drugs of this class (exenatide, liraglutide, lixisenatide, retatrutide, etc.).

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@RapAdmin , @adssx thank you for clarifying. @RapAdmin I know you were doing empagliflozin before, are you still on it, and how do you feel about it in general?? i.e I always come to a conclusion about any substance i take (anecdotal of course, but normally free of placebo effect).

I took it for a few weeks. It makes you pee more, might lower sugar a bit, but I’m keto and I think it’s a much better drug for somebody with a big problem. I found Dapag to be much less of a problem with side effects. Very easy to take. Similar results for me. Don’t know what to think of these drugs either. I’ve switched to metformin for a while.

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I am just about to reorder empagliflizin. I like it. Really good blood glucose control and no noticeable side effects for me

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Is there any reason you chose empagliflozin? (I’ve just re-ordered dapagliflozin 10 mg for the same reason: works great for my reactive hypoglycemia and overall glycemic control and 0 side effects so far.)

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I think he’d mentioned earlier that Cana had given him muscle weakness and he switched to Empa with no side effects. I’ll save him a 30 second response lol

Thanks. But why empa and not dapa or sota? :wink: Also: which empa 10 mg or 25 mg?

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the answer could be the same as you’d answer " why is it raining today in NY", or could have to do with price point and maybe some other consideration. But it is my experience that when something in a field of say 10 things doesn’t work well with you, then just move to the second one with no other apparent reason than just to see if that is better tolerated. I’m sure @admin will give you much more precise answer.

I was just trying a different …flozin, and had not done a ton of research on all the variations. Plus this was a few years ago. Not sure if all the flozins are generic yet.

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