Canagliflozin - Another Top Longevity Drug

Mine was 47 last night, tends to be 48ish

Women tend to be a bit higher than men

A ton of data publicly available online about this

For example below is from Oura

Think Whoop has the same and they both also have it for HRV id I recall correctly


Source and more discussion

What Is the Average Resting Heart Rate? - The Pulse Blog.

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Thanks for the link. Nice to see I’m not as bad as I thought I was.

My lowest HR during sleep, as shown in your chart, is higher than the average (sometimes in the high 50’s but usually low 60s), but my average HR seems to be exactly average… never has being average sounded so good :slight_smile:

And your HR is incredible!!! Along with @John_Hemming

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Thanks for the charts…your data is interesting in the very limited range of your 2025 HR….presume you have a good sleep protocol and are consistent.

In contrast,Oura has my range 41-64 (47 average)

My HR varies based on cardio activity over long term. For example, during 2020 COVID I biked frequently (annual HR 46) but from 2021-23 didn’t train much (annual HR 51 each year). Last year began running and HR returned to mid 40’s (45 annual) and tapered this year (47).

Late snacks/alcohol/stress = high overnight HR IMO

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Oh yes, Oura single handedly turned me into an almost non drinker.

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Altitude seems to have a big impact on my RHR/HRV. I spent all of January skiing and a couple weeks in March and also spent some time in Mexico City, all of which had an immediate effect on my RHR/HRV. Combine that with an increase to 7.5mg of Tirzepatide and that likely explains a significant portion of the average increase for 2025. We’ll see if some consistent training will bring it back down over the year now that I’m done skiing for the season.

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my wife (60) has a RHR of low 60’s with an occasional dip into the high 50’s. She is extremely fit so I’d say your ok.

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Yes, but thinks it’s less about that for me and more about overall expertise / mindfulness practice and:

Late snacks/alcohol/stress = high overnight HR IMO

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Michael Lustgarten has a video or two on this topic and how it changes across age and how it is associated with mortality - you might want to look at that (they tend to just quite short and sweet)

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I thought this was interesting. Tofogliflozin (approved in Japan) causes less urination at night (nocturia) compared to other SGLT2i meds:

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Thanks for that, Davin8r. Tofogliflozin indeed sounds interesting. It is apparently even more selective of SGLT-2 compared to SGLT-1 than empagliflozin. It’s nice wrt. the nocturia, but ultimately what’s really of interest is how it compares to other SGLT2i in various settings, whether glucose control, CV benefits etc. I have not done a deep dive on tofogliflozin, but I did note this paper:

Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial

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SGLT2i benefits for depression: Depression and mental health: what do you use? - #136 by adssx

For dementia: Glucose lowering meds lower dementia risk

Dapagliflozin in PD: Glucose lowering meds lower dementia risk - #5 by adssx

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Are most people getting SGLT2 inhibitors from the same Indian pharmacies you get rapamycin from? Any recommended brands?

Branded Jardiance is available from India, so that’s what I take.

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Direct Cardiac Mechanisms of the Sodium Glucose Co-Transporter 2 Inhibitor Class 2025

This review identified several key mechanisms by which SGLT2 inhibitors may benefit the heart directly, including reductions in oxidative stress, inflammation, and myocardial fibrosis. Emerging evidence suggests that these drugs modulate key pathways such as sodium-hydrogen exchange (NHE) inhibition, improvement of mitochondrial function, and promotion of ketone body utilization in cardiomyocytes.
SGLT2 inhibitors appear to confer direct cardioprotective effects. These include anti-inflammatory, anti-fibrotic, and energy efficiency improvements in the myocardium. The findings highlight new potential therapeutic mechanisms and provide a foundation for further research into the non-diabetic use of SGLT2 inhibitors in heart failure and other cardiac conditions. Understanding these direct effects could lead to optimized treatment strategies for patients with and without diabetes.

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Comparative study of SGLT2 inhibitors and metformin: evaluating first-line therapies for dementia prevention in type 2 diabetes 2025

GLT2is significantly reduced dementia risk and mortality compared to metformin in T2D patients. These findings suggest SGLT2is may offer superior neuroprotective benefits, underscoring their potential as a first-line therapy for T2D. Further randomized trials are needed to confirm these results.

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Nice find. It’s association, but still, the numbers are impressive. Are SGLT2i very good or is metformin very mediocre?

“Results

- Among 74,975 matched patients in each cohort, SGLT2i use was associated with a lower incidence of overall dementia: 2.7% vs. 6.9%: adjusted hazard ratio (aHR) 0.80 [95% CI 0.76;0.84]. Reductions were observed in vascular dementia (0.8% vs. 2.0%; aHR 0.87), Alzheimer’s dementia (1.1% vs. 3.2%; aHR, 0.76), and all-cause mortality (6.8% vs. 15.4%; aHR, 0.92). Benefits were pronounced in older adults, particularly those aged ≥80 years.”

“Benefits were pronounced in older adults, particularly those aged ≥80 years.”

Well, you expect that since dementia (and ACM) increase with age, if there are benefits, they would be more pronounced in older adults.

What would be of interest is how long does one have to be on SGLT2i to start seeing benefits and are these a steady amount per year, or are the benefits cumulative with time beyond that steady level.

Obviously, we are talking about high risk individuals with significant morbidities. How does this map out for people on these agents who don’t have these morbidities, that’s the question for those who take them for longevity/healthspan purposes.

They make a point that of course these are associations, but the RCTs are inconsistent. One wonders about the numbers of people in these RCTs, if adequately powered.

“[…] this association remains unconfirmed due to inconsistent findings across studies, particularly randomized trials.”

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