Is there any data, even if it’s a small sample or anecdotal, on SGLT2 use in athletes? It’d be very interesting to see how it impacts performance in highly trained (or at least somewhat trained) people. Lean muscle mass, strength, VO2 max, etc. I realize that it’s a very different population, but I imagine that even among athletes there may be diabetics, CKD patients, and life extension enthusiasts. Longitudinal data/reports would be especially interesting as I wonder not only whether one can maintain, but improve fitness while on these drugs.
One reason that gives me pause is that low-carb and keto diets have not been shown to be great for high-level performance, at least as I understand the literature as a non-expert, and SGLT2 inhibitors mimic at least some of the effects produced by these diets.
1 Like
adssx
#1067
Chinese paper but looks serious (Shanghai Jiatong + University of HK + some researchers are also in the UK): The effect of SGLT2 inhibition on brain-related phenotypes and aging: a drug target Mendelian randomization study 2024
SGLT2 inhibition was associated with longer father’s attained age (years of life increase per SD (6.75 mmol/mol) reduction in HbA1c levels = 6.21, 95%CI 1.95 to 11.15), better cognitive function (beta = 0.17, 95%CI 0.03 to 0.31) and higher intelligence (beta = 0.47, 95%CI 0.19 to 0.75).
Our study supported that SGLT2 inhibition increases father’s attained age, cognitive function and intelligence, which was mediated through brain images of different brain regions. Future studies are needed to investigate whether similar effect could be observed for users of SGLT2 inhibitors.
The body of evidence in favor of SGLT2 for neuroprotection (at least for men?) is growing quickly… Any thoughts @Guest?
9 Likes
AnUser
#1068
Longer fathers age but not mother’s seem like the ITP result where it only increased lifespan in male mice?
I think it would be interesting to ask Richard Haier (Contact — Richard Haier) an intelligence researcher about the cognitive function / intelligence finding. 0.47 beta which if i I understand it correctly is half a SD or 7 IQ points?
9 Likes
adssx
#1069
Thanks, I’ve just emailed him.
2 Likes
adssx
#1070
Three Chinese papers on cancer with different conclusions:
2 Likes
adssx
#1071
Shared by @CronosTempi: Parkinson's disease - #310 by CronosTempi
SGLT2 Inhibitor Use and Risk of Dementia and Parkinson Disease Among Patients With Type 2 Diabetes
From the 358,862 participants analyzed (mean [SD] age, 57.8 [9.6] years; 58.0% male), 6,837 incident dementia or PD events occurred. Regarding the individual endpoints, SGLT2i use was associated with reduced risks of AD (adjusted hazard ratio [aHR] 0.81, 95% CI 0.76–0.87), VaD (aHR 0.69, 95% CI 0.60–0.78), and PD (aHR 0.80, 95% CI 0.69–0.91) with a 6-month drug use lag period. In addition, use of SGLT2i was associated with a 21% lower risk of all-cause dementia (aHR 0.79, 95% CI 0.69–0.90) and a 22% lower risk of all-cause dementia and PD than use of other OADs (aHR 0.78, 95% CI 0.73–0.83).
I like that they looked at “all-cause dementia and PD” as some interventions can lower the risk of PD but increase the risk of AD (e.g. smoking), or vice-versa. The OR are not as impressive as in other papers but the cohort is massive (1.3 million people).
I wonder what are the most prescribed SGLT2i in Korea.
1 Like
Curious
#1072
An online search mentions Empagliflozin as the most prescribed SGLT2 in Korea.
1 Like
adssx
#1073
Do you have access to the paper @AnUser? Did they look at intra-class differences?
Apparently, dapagliflozin, empagliflozin, ipragliflozin, and ertugliflozin are approved in SK. There are dozens of generic dapagliflozin versions so AstraZeneca left the market this year: NAVLIN DAILY
In this other study that probably looked at the same Korean database, they had the following breakdown: Sodium–glucose cotransporter 2 inhibitors do not increase the risk of fractures in real‐world clinical practice in Korea: A national observational cohort study 2022:
The distribution of specific SGLT2i or DPP‐4i compounds within each group is shown in Table S2. SGLT2i compounds included dapagliflozin (54.3%), empagliflozin (39.2%) and ipragliflozin (6.5%; Table S2).
So dapagliflozin seemed to be the most prescribed in the past, even though empagliflozin recently took over and became market leader (SGLT-2 diabetes drug Jardiance outsells mkt leader Forxiga 2024).
So is the lower HR in this study due to dapagliflozin being used whereas in the US empagliflozin is #1? 
3 Likes
RapAdmin
#1075
Empagliflozin Dampens Doxorubicin-Induced Chemobrain in Rats: The Possible Involvement of Oxidative Stress and PI3K/Akt/mTOR/NF-κB/TNF-α Signaling Pathways.
Abdelsalam RM, Hamam HW, Eissa NM, El-Sahar AE, Essam RM.
Mol Neurobiol. 2024 Sep 20. doi: 10.1007/s12035-024-04499-5. Online ahead of print.
PMID: 39302617
2 Likes
This paper here makes an offhand claim that empagliflozin and canagliflozin are insulin analogues, unlike dapagliflozin and other SGLT2i. I have never come across this claim elsewhere - can someone explain to me how these two in particular are insulin analogues while the others are not?
Key Quote:
“Regarding antidiabetic medication, metformin, gliclazide, pioglitazone, exenatide and dapagliflozin exert a beneficial effect on Endothelial Function (EF); glimepiride and glibenclamide, dipeptidyl peptidase-4 inhibitors and liraglutide have a neutral effect, while studies examining the effect of insulin analogues, empagliflozin and canagliflozin on EF are limited.”
1 Like
raps
#1077
people on off-label SGLT2i: what biomarkers do you check to ensure you’re not hitting any negative side-effects? Also curious for anecdotes on positive side effects (e.g. lower post-prandial blood glucose etc.)
1 Like
I am not on empa, but soon will be. I intend to track my before/after biomarkers, obviously first and foremost blood sugar levels throughout the day, including morning and fasted with the help of a CGM; longer term A1c.
Then, liver and kidney panel for obvoius reasons, but also a basic lipid panel based on this PMID: 27207551
RapAdmin
#1079
The negative side effects you really care about are the ones you can’t help but notice; urinary tract infection, etc. - see full list here: Canagliflozin (Oral Route) Side Effects - Mayo Clinic
But they seem to be relatively rare in healthy populations. I reported on my experience with canagliflozin in this thread: Canagliflozin for Anti-aging (part 2)
Since then I’ve been pulse dosing (month on, month off) empagliflozin generally with good results (no noticeable side effects) - but last month I noticed an increasing level of fatigue that was out of the ordinary after a few weeks of empagliflozin. So - right now I’m off it, and my energy has returned. I had a similar issue with canagliflozin. I’m not sure how I’ll manage this going forward - still evaluating. I also frequently take acarbose, especially on higher starch days when I’m not taking an SGLT2 inhibitor.
1 Like
matthost
#1080
This is very exciting evidence that the lifespan effect will translate to humans.
1 Like
I have lost weight on empagliflozin. That’s great as I am overweight. I have also increased my water intake. I find I am much thirstier. Drinking more water is a bonus IMHO.
4 Likes
tj_long
#1082
Could that just be an error? I can’t find that SGLT2 inhibitors are insulin analogues?
I guess. I just find it really weird that they’d group the SGLTi that way. Both empa and dapa are SGLT2i, whereas cana is SGLT1/2i. Empa and dapa are much closer to each other, both being “2”, so if anything I imagine you’d group these two together. Instead they group empa and cana together, but dapa (presumably with other SGLTi) separately. Go figure. Meanwhile I’m trying to understand how these two are insulin analogues, because what do these two do functionally differently than dapa does?.. all get rid of glucose by a similar mechanism.
I’ve looked through pubmed, but didn’t see any papers reference SGLTi as insulin analogues, nor specifically empa and cana, in opposition to dapa. But I may have missed something.
1 Like
adssx
#1084
Weird. @AnUser if you have access to the full text: do they cite a source to back this claim?
