The research which @adssx posts usually favors empagliflozin over canagliflozin for various benefits. Canagliflozin also has some side effects which are not good. However, Canagliflozin has the ITP data backing it up whereas empagliflozin does not as they havenāt tested it. If the longevity benefits come from SGLT2I, then empagliflozin should be fine. However if the longevity benefits come from SGLT1, then only canagliflozin would work.
I can completely understand why some people would choose Canagliflozin due to the ITP data.
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adssx
#9
One Chinese study found life extension with empagliflozin in rodents as well. And Mendelian randomization shows a causal association between SGLT2 inhibition and male age. So SGLT2i might be enough. (I take dapagliflozin)
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@DeStrider What side effects are you thinking about that are not good that canagliflozin but not empagliflozin?
@adssx Was it this mice study on on empagliflozin that you was thinking about?
āEmpagliflozin extended the median survival of male mice by 5.9%.ā
Source: Empagliflozin rescues lifespan and liver senescence in naturally aged mice - PubMed
Any reason why you take dapagliflozin and not canogliflozin or empagliflozin?
adssx
#11
Yes itās that study.
Canagliflozin has more side effects and less good data in humans (thatās why itās not approved for as many conditions as the others).
Empagliflozin and dapagliflozin seem to be very close. Dapagliflozin has a bit of SGLT1 inhibition as well. I was prescribed dapagliflozin for reactive hypoglycemia so I sticked to it. But I might change to empagliflozin if better data emerges.
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Do you have any post or some linke where I can read more on that canagliflozin has more side effects and less good data in humans?
adssx
#13
You can read the whole thread here 
Or filter on my messages.
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Davin8r
#14
Thanks for that excellent analysis, @CronosTempi
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I just started Brenzavvy (bexagliflozin ). Hereās While Brenzavvy itself has not been extensively studied for longevity benefits, it shares the mechanism of action of other SGLT2 inhibitors that have demonstrated potential in slowing aging and preventing age-related diseases. SGLT2 inhibitors have been associated with reduced risks for common conditions of aging, including heart failure, chronic kidney disease, atrial fibrillation, cancer, gout, neurodegenerative disease, and non-alcoholic fatty liver disease.
A biohacker might consider taking Brenzavvy (bexagliflozin) for its potential longevity and anti-aging benefits, despite it being primarily designed for type 2 diabetes treatment. Hereās why:
- Potential lifespan extension: SGLT2 inhibitors, the class of drugs Brenzavvy belongs to, have shown promise in extending lifespan in animal studies. For example, canagliflozin increased median survival of male mice by 14%[
(Repurposing SGLT-2 Inhibitors to Target Aging: Available Evidence and Molecular Mechanisms - PMC).
- Healthspan improvement: SGLT2 inhibitors have demonstrated the ability to improve healthspan by reducing the incidence or severity of age-related conditions such as cardiomyopathy, kidney disease, and liver issues
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- Cellular senescence reduction: These drugs have shown potential in eliminating senescent cells, which contribute to aging. Canagliflozin, another SGLT2 inhibitor, reduced senescence load in visceral adipose tissue and improved metabolic dysfunction in mice
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- Metabolic benefits: Brenzavvy has been shown to improve glycemic control, reduce body weight, and lower systolic blood pressure, which could contribute to overall health and longevity
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- Anti-inflammatory effects: SGLT2 inhibitors have demonstrated the ability to reduce low-grade inflammation, a key driver of aging often referred to as āinflammagingā
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- Potential neuroprotective effects: Some studies suggest SGLT2 inhibitors may have benefits for the central nervous system, which could be of interest to biohackers looking to optimize cognitive function
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(Not medical advice)
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My Rapa doc here in Colorado just wrote me an Rx of this SGLT2 inhibitor.(Jan 20 2025) and I got it from Mark Cubanās CostPlus drugs - $145 for 90 day supply. I got 90 1mg Sirolimus there too for $90 until CVS started selling it for $75 (using coupons). At age 73, Iāve been getting diminishing returns from rapamycin, and hope that adding this gives me a boost. Thanks for the reference and synopsis - much appreciated.
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Would you mind sharing which sglt2 you purchased from Costplusdrugs? I see dapagliflozin and seems a lot higher than $145 for a 3 month supply.
I talked to my pharmacist regarding the Empagliflozin 25mg.
She said we cant split the tablet since it has film.
Can you confirm this please?
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Davin8r
#19
I used to split my Jardiance in half before I raised the dose to a full tablet, and it definitely still worked (confirmed with multiple urine tests).
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Did you need any splitting tool, or you could just do it with lets say ā¦ knife?
Davin8r
#21
Itās been a while, but I think I just snapped in half with my fingers. Iād never use a knife, in any case, since pill splitters are cheap and far more safe and reliable.
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I have several - like 6-8 - pill splitters lying around somewhere, but Iām too lazy to pull them out, so I just use a knifeš
. No issues. But I do a bit of woodworking as a hobby, so Iām handy with sharp tools, and have a decent eye for measuring. So far so good (on one occasion, I had half the pill pop across the counter and into the sink, lol). YMMV.
Beth
#23
Yesterdayās Attia podcast did a deep dive into SGLT2s.
He was interviewing Ralph DeFronzo who developed them. He was also pivotal in bringing metformin to the US. I learned a lot
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Thereās a lot here to learn. Iāll have to go back and listen again. And probably chrck out this guyās papers.
As an aside, Iāve been wanting Attia to dive a lot more into GLP1 agonists, and this episode is the closest thing to a deep dive that Iāve heard from him. I did not like his alarmist take from 2 years ago on muscle loss and this class of medication.
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Podcast timestamps for highlights
Dangers of too much insulin to manage glucose
#5 in āOminous Octetā: GLP1 and GIP hormones account for 70% of insulin released at meals
Actose (Pioglitoazone) to treat T2D insulin resistance directly
Metformin to treat T2D not very effective, but canāt really hurt unless you get GI side effects from it
Triple Therapy for treating T2D (ie donāt follow the ADA approach which doesnāt treat insulin resistance and Sulfonylureas burn out the pancreas and stop working)
GLP-1s and GIPs (semaglutide & tirzepatideā¦ With retatrutide in phase 3 FDA trials)
Any concerns with long term health using GLP-1s? No, but go slow titrating up to avoid GI issues and work on not losing lean muscle mass by strength training
What has changed in the last 30years that has driven the obesity epidemic? Both environment and genetics. And diabetes can be caused by so many different defects in so many organs, itās ātoo easyā to develop in our environment (epigenetic defects)
TLDR: GLP-1 + Pioglitoazone (+ Metformin doesnāt hurt) for best treatment of T2D
And that every PCP medical professional reads to these studies: Unsupported browser
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Davin8r
#26
This was one of my favorite all-time Attia podcasts. I was riveted the entire time, and I definitely plan to give it a 2nd listen.
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Beth
#27
Iām so pleased to hear you enjoyed it as much as I did. And yessss, I have started my second listen to absorb the parts I missed!
Even Attia was learning throughout the entire podcast. That doesnāt always happen.
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