Canagliflozin - Another Top Longevity Drug

[mchasemd]

@Davin8r

empagliflozin

Both have similar efficacy in improving glycemic parameters and heart failure biomarkers. The price of empagliflozin in the US is somewhere in the range of $550/mo. That bothers me. Empagliflozin is more studied because it is sold in the US (where the most medical research dollars in the world originate). Millions of Indians are on remogliflozin and have been for years and it has shown a good safety profile.

[adssx]

But why not buy empagliflozin from India?

[Davin8r]

Who cares about the price of empagliflozin in the US when you are shopping for meds in India?

[DeStrider]

Also, when you buy Indian Empagliflozin, you can buy the original brand made in Europe and not a generic made in India.

[Ruben2]

Anyone experienced random cold sweats or slight sensation of fever while on empagliflozin? I’m taking 12.5mg irregularly and noticed this happens more often if taking it two days in a row

[Virilius]

My body temperature is elevated on it.

[adssx]

Mendelian randomization study of sodium–glucose cotransporter 2 inhibitors in cardiac and renal diseases 2024
Chinese paper

SGLT2i had a significant protective effect against nephrotic syndrome (odds ratio [OR] 0.0011, 95% confidence interval [CI] 0.000–0.237), chronic glomerulonephritis (OR 0.0002, 95% CI 0.000–0.21), and hypertensive nephropathy (OR 0.0003, 95% CI 0.000–0.785). No causal effects were observed between SGLT2i and cardiac diseases or potential adverse events.

If I understand correct, this finding suggests that SGLT2 inhibition is highly nephroprotective but that SGLT2 inhibitors might not be cardioprotective via SGLT2 inhibition but via another off-target pathway.

[justaguest]

I apologize if this was already discussed, but are there any ideas on why cana led to a more significant increase in mice lifespan in the ITP study than empa did in the study below?

Cana extended median survival of male mice by 14%.

Canagliflozin extends life span in genetically heterogeneous male but not...

Empagliflozin extended the median survival of male mice by 5.9%

Empagliflozin rescues lifespan and liver senescence in naturally aged mice -...

[CronosTempi]

Perhaps it’s overly cautious, but the empag paper is from Chinese institutions that are not of the first order. I think that’s worth noting. Btw., here is Matt Kaeberlein about Chinese papers, having spent a lot of time there on scientific exchanges. He’s very diplomatic, but states outright that once you step outside the few major research centers in Beijing and Shanghai, the quality plunges precipitously, and any smaller regional paper he looks extra cautiouly at - from 4:50 on:

Does NMN Actually Increase VO2 MAX? | 61 - Longevity This Week #9

I’d look for confirmation of these results first before going all in on this. YMMV.

[adssx]

@justaguest

Empagliflozin extended the median survival of male mice by 5.9%

Excellent question! Which dose did the Chinese study use? From which age? Which route of administration?

[adssx]

OK, so the Chinese paper says:

To observe the effect of empagliflozin on the lifespan of mice, 100 13-month-old C57BL/6 J male mice were randomly divided into two groups (n = 50 in each group). Mice received water and standard AIN-93G diet (Ctrl) or standard AIN-93G diet plus empagliflozin 30 mg/kg/day body weight (Empa) ad libitum. Mice were observed daily, and their mortality was recorded. In addition, mice were euthanized for humane reasons if they were found to be in a severely distressed state by an experienced professional technician and unlikely to survive more than 48 h.

And they found “Empagliflozin extended the median survival of male mice by 5.9%”, log-rank survival test analysis, P = 0.0274

The ITP using canagliflozin:

• 2016: 180 ppm (equivalent to 30 mg/kg mouse body weight), from 7 mo: +14% median survival of male mice, log-rank test yielded P < 0.001, 150 male controls + 150 male cana
• 2020, 180 ppm (idem), from 16 mo: +14% median survival of male mice, p = 0.004, same numbers?

The ITP uses “genetically heterogeneous (UM-HET3) mice born in 2016 were placed on a chow diet”.

So:

1. The types of mice and diet might influence the results.
2. The Chinese study was 3x smaller. It’s possible that the “real” lifespan extension is not that different between empa and cana.
3. The ITP paper notes that the cana dose used is “similar to the human therapeutic dose of 100–300 mg/d for a 70 kg person”. The Chinese study used the same mg/kg/day dose of empa. However, in humans the typical dose (DDD) is 200 mg for cana vs 17.5 mg for empa. 11x more! So they should have tested empa 3 mg/kg/day.

However, assuming the Chinese study is correct, it’s still interesting: empagliflozin, contrary to canagliflozin, is a pure SGLT2 inhibitor so it shows that SGLT2 inhibition alone might have life extension properties (or it’s an off-target mechanism common to canagliflozin and empagliflozin?). poke @Neo.

[Virilius]

Empagliflozin has still shown significant benefit in protecting kidney function in human clinical trials so regardless of how well it works in male mice, everyone should still be using it.

[Dexter_Scott]

My own experience with Jardiance has not been encouraging. Have only been using it for a short time, and already had two bladder infections that involved a week of frequent urination, painful urination, and extreme fatigue. Going to talk to my cardiologist next week about it. As I’m not diabetic I don’t “need” to be on it and I’m wondering if perhaps a lower dose or cycling on/off would be more viable.

[Davin8r]

Interesting. Even when I had severe prostate hyperplasia with severe urinary retention, I never had a single UTI while taking empagliflozin.

[nikney]

You are not diabetic, have you tried taking it at a lower dose and only a few days a week?

[adssx]

This is already approved for non diabetic who have CKD or heart failure so it shouldn’t be a problem.

[AnUser]

What about UTI vaccine before using SGLT2i? I see no mention of Uromune here: Uromune - Wikipedia

There is also a UTI vaccine trial which is possible to enroll in following certain criteria.

[justaguest]

Two (naive?) questions I’ve been wondering about:

1. Do we know anything about the body’s adaptations during the time SGLT2 inhibitors are taken that may impact what happens after discontinuing them? In other words, what would happen if one tried these drugs for several months or years but then discontinued them? Would the body revert to “business as usual”, or is it possible that there would be some residual (especially unwanted) effects due to some feedback mechanisms?
2. Somewhat related, most of the studies are relatively short-term. Is there reason to believe that the positive effects discussed in the thread would continue compounding if the drugs are taken long-term (5+ years, 10+ years, etc.), or is there a risk that the trend would eventually reverse?

[Virilius]

There is no reason to believe that the body would not reverse to its default state after SGLT2 inhibition is stopped. At the very least there are no case reports pointing to such a thing.

[Dexter_Scott]

Not yet, I’m going to see what the doc says next week.