#352

Sodium-glucose cotransporter 2 (SLGT2) inhibitor use was associated with a significantly lower risk of sight-threatening retinopathy than dipeptidyl peptidase-4 inhibitors, pioglitazone, and sulfonylureas among patients with type 2 diabetes (T2D), according to new research.1

Across the nationwide cohort in Taiwan, the potential protective role of SGLT2 inhibitors for sight-threatening retinopathy was observed across various subgroups of patients, including by age, sex, comorbidities, and medication use.

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#353

Amazing, thanks for sharing!

Artigo completo: Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Retinopathy in Type 2 Diabetes

“In matched patients, empagliflozin, dapagliflozin, and canagliflozin were associated with a significantly lower risk of sight-threatening retinopathy than DPP-4i, pioglitazone, and sulfonylureas (eg, vs DPP-4i: AHR, 0.53 [95% CI, 0.40-0.72]; 0.54 [95% CI, 0.48-0.62]; and 0.65 [95% CI, 0.57-0.74], respectively; P < .001) (eTable 5 in Supplement 1). Also in the matched cohorts, SGLT2i compared with DPP-4I, pioglitazone, and sulfonylurea was associated with a significantly lower risk of dialysis (eg, vs DPP-4i: AHR, 0.05; 95% CI, 0.03-0.08; P < .001), hospitalizations for heart failure (eg, vs DPP-4i: AHR, 0.47; 95% CI, 0.41-0.52; P < .001), and severe hypoglycemia (eg, vs DPP-4i: AHR, 0.44; 95% CI, 0.38-0.51; P < .001) (eTable 6 in Supplement 1).”

“Another meta-analysis reported that ertugliflozin and empagliflozin could reduce the risk of retinal disease, whereas canagliflozin could increase the risk of vitreous disease.”

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#354

I dug a bit more, eTable 5 in Supplement 1 (“Supplemental content” tab) shows that empagliflozin and dapagliflozin are way more protective than canagliflozin to lower the risk of sight-threatening retinopathy. Empa and data are almost identical (except when compared to Pioglitazone, where empa is way better than dapa). However, empa has tiny numbers of users, although the results are still statistically significant, so I would not be surprised if, with larger numbers, empa was shown to be more protective than dapa.

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#355

Old paper (2014) but good charts: Dapagliflozin as Monotherapy in Drug-Naive Asian Patients With Type 2 Diabetes Mellitus: A Randomized, Blinded, Prospective Phase III Study

Figure 2 shows:

  • Effect on fasting plasma glucose (FPG) reached after about 1 week
  • Effect on Hb A1c reached after about 2 months
  • Effect on weight loss reached after about 3 months
  • For FPG, Hb A1c and weight loss, dapagliflozin 10 mg was more effective than dapagliflozin 5 mg.

Over 24 weeks, the % of adverse events was lower in dapagliflozin vs placebo, while the % of serious AEs occurred in 1.5% (placebo), 3.9% (dapagliflozin 5 mg), and 3.0% of patients (dapagliflozin 10 mg). However, there were more genital infections and UTIs in dapagliflozin 10 mg compared to dapagliflozin 5 mg. So dapagliflozin 10 mg is overall more effective with fewer adverse events and serious adverse events than dapagliflozin 5 mg except for genital and urinary tract infections.

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#356

An Accidental Breakthrough: A Drug Designed to Treat Diabetes Appears to Slow Aging and Forestall Death

By mimicking the effects of fasting, SGLT inhibitors seem to broadly counteract age-related diseases and decline.

Dr. James O’Keefe is no pill-pusher.

As director of preventive cardiology at Saint Luke’s Mid America Heart Institute, O’Keefe has spent much of his career studying how a proper diet, exercise, and other tried-and-true health behaviors protect against the perils of aging.

During our past conversations, O’Keefe, who is also a professor of medicine at the University of Missouri-Kansas City, has bemoaned the sorry state of American healthcare, which he says is structured to treat illness rather than prevent people from getting ill in the first place. “The sicker the population, the better that is for hospitals, drugmakers — the whole system,” he says.

‘I’ve been a physician for 40 years, and I’ve never been so excited about a medication for human health and longevity.’

O’Keefe is an unlikely evangelist for a novel pill-based solution to the problem of age-related disease and infirmity. But he says that his personal experience treating patients with SGLT inhibitors — coupled with his own just-published research into the effects of these medications — has convinced him that they “are truly revolutionary.”

“If you look at how the survival curves separate for people on these drugs versus people on placebo — I have never seen anything like this in my career. Not even close,” he said of the once-daily pill’s apparent ability to extend life and prevent a range of age-related diseases.

“I have no doubt this therapy is going to change the landscape of aging and age-related disease,” he added.

Artigo completo aqui: https://archive.ph/yBDlN

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#357

With the actual paper + a connect to another tread from today

SGLT inhibitors for improving Healthspan and lifespan

Sodium-glucose cotransporter inhibitor/inhibition (SGLTi), initially approved as a glucose-lowering therapy for type 2 diabetes, is associated with decreased risks for many of the most common conditions of aging, including heart failure, chronic kidney disease, all-cause hospitalization, atrial fibrillation, cancer, gout, emphysema, neurodegenerative disease/dementia, emphysema, non-alcoholic fatty liver disease, atherosclerotic disease, and infections. Studies also show that SGLTi improves overall life expectancy and reduces risks of cardiovascular death and cancer death. These wide-ranging health benefits are largely unexplained by the SGLTi’s modest improvements in standard risk factors. SGLTi produces upregulation of nutrient deprivation signaling and downregulation of nutrient surplus signaling. This in turn promotes autophagy, which helps to optimize cellular integrity and prevent apoptotic cell death. SGLTi decreases oxidative stress and endoplasmic reticulum stress, restores of mitochondrial health, stimulates mitochondrial biogenesis, and diminishes proinflammatory and profibrotic pathways. These actions help to revitalize senescent cells, tissues, and organs. In summary, SGLTi appears to slow aging, prevent disease, and improve life expectancy, and its mechanisms of action lend strong biological plausibility to this hypothesis. Further randomized trials are warranted to test whether SGLTi, a safe and well-tolerated, once-daily pill, might improve healthspan and lifespan.

https://www.sciencedirect.com/science/article/pii/S0033062023001068

Together with below seems to make it even more attractive to consider

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#358

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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#359

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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#360

+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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#361

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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#362

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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#363

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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Parkinson's disease
#364

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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#365

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

#366

This link seems to be about semaglutide, not empagliflozin.

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#367

aren’t they both SGLT2 inhibitors?

#368

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

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#369

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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#370

@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).

#371

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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