#1226

From the study:

“In numerous studies, the dementia prevalence rate in patients with type 2 diabetes was higher than in patients without type 2 diabetes.”

SGLT2i users in their study had lower rates of dementia across age groups. But how much higher are the dementia rates among T2DM patients compared to nondiabetics in Taiwan. The question is whether the SGLT2i users had lower rates of dementia compared to nondiabetics, not just diabetic non users of SGLT2i meds.

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#1227

This is not “the” question.

The increased risk of dementia among people with T2D vs non T2D is about 60%. And SGLT2i users with T2D have a 0.6 risk of dementia vs non users. So theoretically we have 1.6x0.6=0.96, so potentially a tiny bit lower than non diabetics not using SGLT2i. “The” question is whether the HR is the same among pre-diabetics and normoglycemic people. I wish they could look at dementia rates among CKD patients as well.

If the rate is significantly lower with SGLT2i despite their minor glucose-lowering effect it points to potential off target effects compared to other diabetes drugs that are more potent.

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#1228

OK, but they do speculate about the dementia lowering effect of SGLT2i users being down to the SGLT2i not merely as associated with the glucose lowering effect, otherwise any glucose lowering meds should have the same dementia lowering effect. Instead, they speculate that it’s the totality of the SGLT2i actions, including the effect of lowering BP. Also SGLT2i as compared to other T2DM med classes.

The title itself says “correlation”. But assuming a causative effect, is it the same for nondiabtic users of SGLT2i meds vs dementia, because the other potential factors of for example BP are present in both populations, even if at different rates. One would have to also disentangle the effects of BP meds in both.

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#1229

Metformin and exercise don’t mix. What about SGLT2i (dapagliflozin) - not great:

https://academic.oup.com/jcem/article/104/6/1953/5262416

Quote:

"Conclusion

The efficacy of combining two beneficial antidiabetes interventions, regular endurance exercise and SGLT2 inhibition, was not supported. SGLT2 inhibition blunted endurance exercise training–induced improvements in insulin sensitivity, independent of effects on aerobic fitness or body composition."

Note: sedentary, obese subjects.

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#1230

Kind of a bummer that there’s evidence that Metformin, Acarbose, and SGLT2’s all have negative effects on exercise

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#1231

I tried it for months hoping I would adapt to the digestive issues eventually. No luck. Can’t tolerate it.

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#1232

Wait, acarbose too? Even if the drug barely leaves the gut? I assume it may just come from slower carb absorption

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#1233

As far as exercise goes, I felt that SGLT2 (EMPA) was worse for me, then Acarbose was next or almost equally as bad, and then Metformin (mind you I was only taking 500mg, don’t know if higher doses have different effect) which had a much smaller effect almost hard to notice. So, there you have it a N=1 experience on these three meds.

I must also add that Retatrutide is equally as bad for exercise, but that I can understand and accept since I’m taking it to lose weight.

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#1234

I don’t have any issues with acarbose. As you noted, it’s not systematically absorbed and just blocks the slicing of carbs into glucose.
I don’t have any issues with Empagliflozin either it seems. Just ran a 5k in 24:00 and my VO2 max still stays around 48~50 after 4 months.
That said, I eat low carbs and exercise fasted so my liver makes my own glucose (too much of it even).

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#1235

The evidence is mixed
Association of Acarbose with Decreased Muscle Mass and Function in Patients with Type 2 Diabetes: A Retrospective, Cross-Sectional Study - PMC.
I don’t believe these patients worked out though, so maybe training offsets this. Still, it isn’t great news.

This one is better news

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#1236

The picture for SGLT2i and exercise adaptations doesn’t seem as bad as I thought, although of course we don’t know what happens in non-obese subjects without diabetes or heart failure:

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#1237

Well, we do know our hearts and kidneys will be more protected from bad things happening to them. So that’s good

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#1238

I have found the same: persistently elevated A1C, finally reaching 5.8 despite dropping virtually all carbs and exercising heavily (9000 steps daily on the backside of a dam, including double steps for the last 10% to induce high lactate levels (> 10.0 using calibrated lactate meter), and fasting ~16-18 hrs per day. I started remogliflozin, a shorter acting gliflozin out of India, taking it before the 2 meals I eat daily. I like that it is shorter acting and I can take in anticipation of a meal. Works very well (40 mg/dl drop typically post-prandial compared to before remogliflozin). My average CGM readings, averaging over days, dropped to 96 (so likely an A1C of 5.0). My weight has finally stabilized as I added some carbs back to my diet (keto bread, for example). I too was a gluconeogenic machine. Interestingly, the same phenomenon is found with my identical twin brother.

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#1239

In this study SGLT2i did not negatively impact any metric of endurance adaptation.

The only difference was than the SGLT2i inhibitor group did not improve in insulin sensitivity whereas the placebo group did.

Strange since in all other studies on SGLT2i the opposite is observed. Maybe it’s just a fluke…

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#1240

I did follow the entire thread, having said that, I’m still wondering which of the SGLT2i’s members here have chosen to use - and what your argumentation is.
Do members stick with Canagliflozin, because of the ITP or the paper that suggested it may eliminate senescent cells, its effects on Mitochondrial Respiratory Complex I, the fact it seems to be a stronger AMPK activator. Or rather Empagliflozin given the papers that show a greater reduction in major adverse cardiovascular events, CV death, heart failure. Etc.

  • Dapagiflozin

  • Canagliflozin

  • Empagliflozin

  • Another SGLT2 inhibitor

Would also love to hear about potential changes in blood/biomarkers, and/or potential side-effects. @RapAdmin if you don’t mind me asking, didn’t you stop taking Canagliflozin years ago because of side-effects and started taking Empagliflozin - sorry if I may remember this wrong.

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#1241

I picked empagliflozin since it doesn’t have the bad side effects that Canagliflozin has. I use other supplements to prevent (instead of remove).senescent cells (Rapamycin and Taurine). I also prefer the cardiovascular benefits.

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#1242

Thought they might hypothetically slow down senescent build up, but do they actually remove?

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#1243

Thats true. Now I alternate between acarbose and empagliflozin.

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#1244

Yes. They slow down the formation of senescent cells so you have fewer. They decrease the number of senescence overall through prevention. They don’t remove senescent cells.

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#1245

What do people think of this commentary on SGLT2 as senolytics?

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