Canagliflozin - Another Top Longevity Drug

[RapAdmin]

@Davin8r

syncope and carotid artery occlusion/carotid artery stenosis are worth attention.

Interesting…

Syncope (medicine)

Carotid Artery Stenosis: Causes, Symptoms and Treatment

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We discussed it here (and after): Canagliflozin - Another Top Longevity Drug - #1438 by CronosTempi

Chinese paper from a Tier 4 Chinese uni (ranked 201 in China: ShanghaiRanking-Univiersities ). Weird findings. For instance “dementia (RR = 1.29; 95% CI = 0.78-2.12; P = 0.32)” whereas all the papers I saw found a neutral or protective effect on dementia, so unlikely to be 1.29. I would discard the paper entirely.

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Turkish review: SGLT-2 inhibitors on cardiac autonomic function in individuals with and without type 2 diabetes mellitus 2025

SGLT-2 inhibitors reduce sympathetic overactivity and enhance parasympathetic tone.
SGLT-2 inhibitors boost RMSSD and SDNN and lower the LF/HF ratio.
Use of SGLT-2 inhibitors offers anti-inflammatory, endothelial, and baroreceptor benefits.
Standardized HRV studies and nonlinear analysis required

[CronosTempi]

I wonder if they ever explore how long and at what dose of any given SGLT2i do you have to be exposed to in order to register these various effects. Example, 2 years of 25mg/day empagliflozin results in 0.83 HR for heart failure or whatnot. And so on for each effect. It stands to reason that the time of exposure will differ for various effects. I also wonder if the time is different for diabetics and nondiabetics.

[Neo]

Did your HRV change after starting SGLT2i?

Anyone else have the before after date on that?

[adssx]

Unfortunately I don’t have the before/after. But @Davin8r ran the test the other way around: Canagliflozin - Another Top Longevity Drug - #1295 by Davin8r

[Neo]

@Davin8r

When I ran out of empagliflozin while on tirzepatide a few months ago, I almost immediately noticed increased anxiety, heart palpitations, HR and even lower HRV than I already had from low dose tirzepatide. I couldn’t think of a mechanism by which empagliflozin would have made a difference (until now), so I wasn’t sure what to think, but it all got better very quickly after restarting the empagliflozin.

Can you look back at your HRV to see if it changed when you first started emp also?

@RapAdmin - I believe you cycle on and off sglt2i, do you see anything in your HRV data?

[Davin8r]

Sorry, I don’t have the dates dialed in. The difference objectively was mild since I still had (and have) elevated HR and lower HRV while on low dose tirzepatide despite also being on 25mg empagliflozin daily. The subjective difference was much more profound, for whatever reason. Once I got back on empa, my HR was no longer noticeable, no palpitations or anxiety.

[Davin8r]

And this from Lustgarden this morning. Hopefully there isn’t a long-term trade-off between health benefits of incretin mimetics vs the side effects of elevated HR:

Heart Rate Reduction Extends Lifespan

[dicarlo2]

I’ll add that it appears that GLP-1s directly cause the heart to beat faster, as opposed to some other effect eg via the autonomic nervous system.

Experience with GLP-1s

I took another look at the article and it’s actually quite interesting. The authors found that, at least in pigs, the autonomic nervous system is not involved at all in the change in heart rate. This is in contrast to mice and rats where the autonomic nervous system IS involved. So it could be a rather benign increase via direct action on GLP-1 receptors on the heart.

Also note that Ivabradine does not typically have a heart rate lowering effect beyond 60 bpm. So for many health conscious people, it’s not a viable option for further reducing heart rate.

I’m glad he points out that we don’t know if heart rate change itself is causal vs some other related system, eg autonomic function. We do have MR studies that show lower heart rate is better, but I’m not sure if those studies definitively show that lowering (or increasing) heart rate directly via GLP-1s or Ivabradine or beta blockers would have an effect on mortality.

[Beth]

On that note… I’ve been curious about other people’s sleeping heart rates

I think mine is on the high side. According to Oura, my average overnight HR is almost always in the 60s. I’ll have nights here or there in the 70s, but usually it’s been in the mid to high 60s. Over the last month, it dropped to lower 60s, but this week it’s up again.

[John_Hemming]

Mine moves around depending on lots of things many of which are predictable. Last night’s fitbit average sleeping HR was 50, it sometimes goes lower. However, post binge drinking it will be in the 60s and 70s.

[Neo]

@Beth

I’ve been curious about other people’s sleeping heart rates

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.

[Beth]

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

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

[Zag]

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

[Beth]

@Zag

Late snacks/alcohol/stress = high overnight HR IMO

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

[dicarlo2]

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.

[Paul]

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.

[Neo]

@Zag

presume you have a good sleep protocol and are consistent.

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

[Neo]

@Beth

Thanks for the link.

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)