I have hard time understanding this study (I’m sure I’m missing something). Why would placebo group have a 65% increase in telomere, that is huge? and how was it measured? I’m assuming it was a before and after measurement, or probably it was compared to a controlled group of random (other) people?
I mean what the heck if placebo gives an increase of 65% might as well take the placebo? Unless I’m missing something, this is very weird. I mean I’ve seen placebo have say an effect of 10% on other studies but 65% is HUGE. As it stands right now, I have zero confidence in this study. You don’t just feed people corn starch/placebo and all of the sudden their telomeres lengthen by 65%.
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I switched from metformin to an slgt2. I am a 53 year old male and I noticed no difference in strength or muscle size. That said, I am much more veiny. Keeping fat off always take work but it is less work with an slgt2. I get lots of compliments on my low body fat percentage at the gym and in public.
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Hormone replacement therapy would offset this imo. Same with muscle loss on GLP1s.
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Dissecting out the unexpected effects of SGLT2 inhibitors on human aging
https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgag207/8677988?
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Was there any dose specific data or is it in general terms.
It’s a comprehensive review paper. It not only discusses their glucose lowering properties (and related effects) but also other systemic effects. Overall, the author’s conclusion is to be careful with off-label use until more data is available. (I think all scientists would generally strike this tone at this point…we are a careful lot).
From the Conclusions " Collectively, SGLT2 inhibitors must ultimately demonstrate
their antiaging efficacy as well as safety in clinical studies before
they can be implemented as senotherapeutics in society. At present,
it is essential to avoid premature clinical use based solely
on encouraging findings from preclinical studies. In reality, conducting
clinical trials that evaluate antiaging effects using hard
endpoints such as lifespan is impractical due to the requirement
of enormous sample size, long intervention and/or observation
periods, and prohibitive costs required. To address this challenge,
we have started a clinical study in older adults that evaluates
antiaging effects by measuring biological age estimated by
epigenetic clocks method in peripheral blood leukocytes (Trial
ID: jRCTs031250234). If this study demonstrates that SGLT2 inhibitors
attenuate the progression of biological aging, it would
represent a major advance with substantial scientific and societal
implications.
Nevertheless, it is crucial to emphasize that the antiaging or
senolytic effects of SGLT2 inhibitors in humans remain unproven.
Off-label use for antiaging purposes should therefore be strictly
avoided at this stage. Carefully designed, adequately powered
clinical trials are required to determine whether these agents truly
modify biological aging processes in humans. Importantly, reductions
in cardiovascular or renal events do not automatically
equate to slow biological aging and validated aging biomarkers
must be rigorously evaluated.
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Thanks, @WJ_PhD !
Essentially, you should not count on being able to take it and get anti-aging effects, it’s a giant gamble.
They suggest that unless you have an SGLT2i prescribed for some indication, taking it off label is an unquantified risk.
Bottom line, as so often, everyone must do a risk/reward analysis for their own medical situation.
I have elected to take empagliflozin 25mg/day despite having no condition for which this med is officially indicated - though I am prediabetic and even though my PCP would not prescribe it for me unless I become officially diabetic, I think in my case it’s reasonable. But even if I was not prediabetic, I would still take it. I base that on research suggesting that renal protection effects in non-impaired kidneys (healthy) are still present - I am 68, and kidney function declines with age. Getting rid of glucose I see as a win regardless, and research suggests that it may slow the progression to diabetes. That is all I am hoping for, if there is more, that’s icing on the cake. Then I have to ask what are the possible downsides or risk for these speculative benefits. Well, it seems relatively safe for a male with no history of urogenital infections. YMMV, and everyone will make their own decision, but those are my considerations.
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thanks @WJ_PhD and @CronosTempi . Yeah, I’ve been taking it for more than a year now at 12.5mg daily, but I tend to like it as I haven’t been able to notice any side effects not even any muscle aches nor any effect on exercise (which metformin seems to have).
So, my dilemma was more to do with the dosing as I’m tempted to go to 25mg Empagliflozin and maybe scrap metformin (currently do 1000mg daily). I actually like metformin also especially when I take in the evening either with my dinner or before bed, but everyone is saying it effects exercise (not able to confirm nor deny as I do very light exercises and wouldn’t be able to tell either way).
@CronosTempi, do you think you experienced any side effects at that dose, which seems to be the maximum recommended for Diabetes, i.e. did it affect your exercise, or any aches etc…
No side effects whatsoever that I could tell.
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Oh come on, you have to pee an extra 5 times a day and a couple more at night with empag.
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Not true for me, but I may be in a specific situation insofar as I have always peed with a fairly high frequency, because I make sure to always drink a pretty high volume of liquids, so I doubt empaglifozin would necessarily increase the already high frequency.
Not for me either
Do they cite the Mendelian randomization showing increased lifespan in males and increased IQ?
If not then it’s a low-quality review.
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I noticed no diuretic effect either - which may mean it isn’t really doing much.
If you notice a diuretic effect, isn’t that because you spike your sugars high and subsequently dump them. So everyone is going to be different.
And if you have a strong diuretic effect, definitely keep taking it and maybe up the acarbose or watch sugar intake.
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There is no diuretic effect:
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Not for me either.
Has anyone read the paper? I’ve only been able to read the Abstract, which of course doesn’t mention Mendelian randomization.
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If it hasn’t already been posted - a short 16 minute talk at ARDD2025 about 8 short term studies experimenting with SGLT2i off-label in “normal” people (younger that 60, no diabetes, no CKD, no HF ):
This can produce valuable information, as there is the core argument, that SGLT2i are simply normalizing detrimental effects of diabetes/CKD.
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Thanks for sharing. Gemini summary (bold mine):
- Overview & Aim: The presentation discusses evaluating whether FDA-approved SGLT2 inhibitors (traditionally used for diabetes, kidney disease, and heart failure) can be repurposed as gerotherapeutics to optimize healthspan and lifespan in individuals without these diseases [03:30], [10:23].
- Mechanism: SGLT2 inhibitors work by inhibiting glucose reabsorption in the kidneys, causing the body to excrete glucose through urine [03:44]. This pleiotropic drug lowers blood pressure and offers systemic metabolic and cardiac benefits [04:12].
- Systematic Review Findings: A massive systematic review screened over 44,000 articles, ultimately analyzing 536 human studies [07:19].
- Off-Label Data: Looking strictly at 8 completed trials involving younger, conventionally “healthy” cohorts (ages 30–60) taking the drug off-label, SGLT2 inhibitors showed highly positive, statistically significant improvements across multiple organ systems—specifically cardiovascular, metabolic, renal, hepatic, and adiposity systems [08:31], [09:49].
- Research Gaps: Current off-label data severely lacks insights into how SGLT2i impacts the reproductive, immune, and nervous systems [10:51].
- The HEARTS Trial: To fill these gaps, a multi-disciplinary, 6-month clinical trial is being launched in Singapore [11:53]. It will evaluate the effects of 10mg of daily SGLT2i on healthy individuals (ages 35–65) with an optimal BMI, focusing on VO2 max as the primary outcome alongside digital and biological biomarkers [12:11].
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