Is Acarbose Safer than Canagliflozin (Cana)/SGLT2 inhibitors re Longevity?

I’m unsure if this is a function of the paucity of literature examining acarbose in the West, but it seems that while both medications are generally safe, Cana (SGLT2 inhibitors generally) has been identified as having some serious side effects (heightened cardiovascular risk esp when first starting treatment, bone fracture/density issues such risk increasing with treatment duration, ketoacidosis, acute kidney injury, amputation risk, Fournier’s gangrene (a genital infection that can kill you :scream_cat:?!), elevated blood acid levels and urinary tract infections etc). I have not seen quite as concerning a list for acarbose.

Given we are all seeking these interventions for longevity purposes, we need to balance the knowable and quantifiable risk of harm vs a speculative benefit while also having due regard for protocol adherence. Acarbose (50mg 2x day over 5 days) has definitely given my stomach a run (pun intended I think) for its money and I have generally found Cana SIGNIFICANTLY more easily tolerated (100mg once a day over past 4 days) but when considering potential harm it seems Cana should be dispensed with if acarbose issues can be endured.

Oh wise community, what say you?

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They work completely differently and one is not substitute for the other. Acarbose is good at reducing postprandial sugar spike, SGLT2 inhibitors work at reducing the maximum level of BS but have no effect on postprandial BS. There is not much of longevity research of SGL2 inhibitors in non diabetic, so anything is more or less speculative. They do reduce BP, which might be helpful in longevity and non diabetic people taking SLGT2 inhibitors should not be so much affected by urinary track infections as their BS would rarely go above threshold when they start working and secreting sugar into urine thus producing sweet urine, which is basically breeding ground for different bacteria. Acarbose has also effect on microbiome which might be one of the reasons it effects longevity, not only BS regulation. Have also a look here:

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Thank you for your input.

Well I was aware they worked completely differently for diabetes. Though I admit I was (am?) embarrassingly ignorant of the contention that the ITP results for Cana could not-in theory for that is all we have to go one here-be replicable for humans. Having said this, this is NOT the result of skim reading on my part but actually based on what physicians were saying-on Y-Tube Dr Peter Attia has mentioned Cana as a promising drug for longevity (I think he even said something akin to it being a more “elegant” acarbose) and even the doctor monitoring the use of my longevity therapies suggested Cana as a possible candidate (he has prescribed acarbose initially to be fair).

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Also, since I shamelessly seek the perspective of the well-informed, what’s your view of metformin? My-lets say “longevity”-doctor was open to its use but more skeptical of it vs Cana and acarbose based on available data.

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I have both prescribed, but take only acarbose ATM. I will try SLGT2i when I am more comfortable with current regimen I guess. I am more interested in their mild diuretic effect and BP reduction TBH ATM. My husband (MD, who prescribed both) seem quite keen on SLG2i though. There is some possible caloric loss trough excretion of glucose too. But I prefer acarbose as it does not work systemically and mostly inhibits CH digestion in small intestine and reduces glucose uptake and they are digested in colon mostly as short-chain fatty acids (SCFA).

I am really not keen on Metformin. This article in NYT sealed it for me I guess.

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The effect on muscle synthesis did it for me (well and that it failed ITP). Having said this, Dr Nir Barzilai contends that while muscle volume is impacted by metformin, overall strength is not.

You have added further evidence that the side effect profile for Cana is not worth the even more speculative longevity benefits.

Obliged

I have the same perception that you do… acarbose seems to have many fewer serious side effects, but more common annoying side effects.

The SGLT2 inhibitors have fewer annoying side effects, but more potentially serious side effects.

Acarbose has been around a lot longer than the SGLT2 inhibitors - so it is well proven, safe and generally effective ( but depending on your diet, potentially problematic in the GI / Gas category).

I generally have found Empagliflozin to be side effect free - but the research does suggest a small, but real, risk of some more significant side effects like UTIs, etc.

But remember, the typical patient population for the SGLT2 inhibitors are pretty metabolically sick people… so they are likely on other medications, overweight, etc. No studies have been done on healthy people.

I found metformin very effective at quickly reducing weight by 15lbs or so over 8 weeks. But don’t think that its worth it longer term.

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And your view of @scta123 assertion that Cana is ineffectual for longevity?

Canagliflozin was what tested so well in the ITP study - so thats the best data we have in it being very effective for longevity. Whether Canagliflozin is better or less effective than other SGLT2 inhibitors is unknown right now.

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Indeed. It was interesting to note the statement that @scta123 cited that Cana would need to be consumed at a dose of 300mg prior to every meal to be somewhat effective -at least as an acarbose mimic. Whether acting in a similar manner to acarbose is what would provide the longevity benefit in humans, it’s not my place to theorise.

So much is speculative at this point re the longevity protocol for any drug that I prefer safety over everyday comfort.

Let’s hope the body acclimates to acarbose over time.

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I thought the recommended dosage of Cana and Empa was 25 mg ONCE A DAY in the morning? Acarbose is recommended prior to each meal.

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Yes - once per day, morning.

https://www.mayoclinic.org/drugs-supplements/canagliflozin-oral-route/proper-use/drg-20060957

https://www.mayoclinic.org/drugs-supplements/empagliflozin-oral-route/proper-use/drg-20113010

Cana is only sold I believe in 100mg or 300mg doses and for diabetes at any rate one is meant to start with 100mg and depending on outcome/tolerance increase to 300mg (that’s daily).

Empa comes and is taken in different dosages.

I think people are missing the point of why SGLT2’s are so good. I see a lot of comments about diabetes, but their main strength is that they treat (and therefore also prevent) cardiovascular and kidney disease.

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I think the literature points to reduction in cardiovascular events and protective aspects versus kidney cancer for acarbose as well. Whether it’s as efficacious as SGLT2 inhibitors for these diseases I can’t say, but def if one is taking such drugs long term for longevity primarily, I would prefer a drug with a safer general profile, particularly where range of benefits are similar (and of course the data re ITP favors acarbose atm).

What’s unsafe about Empagliflozin? Both drugs seem pretty safe to me unless I missed something.

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There are a some instances of serious side effects with SGLT2 inhibitors… of course they are typically used by pretty sick people, so how these risks translate to healthy people is anyone’s guess. The most serious that I’ve seen people mention here are urinary tract infections… which typically are not that serious (greater sugar in your urine is a good breeding ground for bacteria).

Details: https://www.drugwatch.com/sglt2-inhibitors/side-effects/

and: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368009/

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You are right that it’s generally safe. But if you look at my original post you will note the instances of serious side effects that have been recorded. Acarbose generally lacks a profile of such serious adverse reactions. So it’s not so much that Empa is dangerous-that is not the contention, but rather which drug between acarbose and empa is seemingly safer for the long term user. Given there is more evidence for acarbose efficacy re longevity than empa and given its seemingly safer profile (relatively speaking)- for me the choice is straightforward.

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Acarbose certainly the safer of the two. I have tried both and stopped both because of side effects.

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