A calorie deficit is an mTOR inhibitor, so quite naturally the body leans more catabolic than anabolic, thus affecting muscle tissue (muscles are metabolically quite expensive to maintain, so if calories are in deficit, you lose some). The flip side of that is that caloric restriction, i.e. CR, is longevity promoting (up to a point), at least in part because the resulting catabolism is a chance for the body to get rid of misfolded and otherwise damaged and subpar proteins through autophagy, a kind of house cleaning. Valter Longoās idea behind the Fasting Mimicking Diet is to induce autophagy through a mild calorie deficit and other mTOR inhibitors such as aminoacid (protein) restriction, and do this on a schedule where once youāve done your autophagic house cleaning you go back to the anabolic state to build back the tissues with healthy cells having got rid of the damaged cells. The once weekly rapa schedule many here are practising, are trying for the same thing - cleanup, build back. Matt Kaeberlein appears to pulse his rapa even more strongly, doing it biweekly, and then taking regular rapa holidays of several months.
Bottom line, calorie deficit being an mTOR inhibitor signal quite naturally results in some loss of muscle, but arguably, you are losing the subpar cells, so thatās healthy overall. Rapa seems to bear this out as there are reports that you actually gain muscle with rapa interventions, perhaps in the quality department, something that the Brad Stanfield study aims to explore. Itās similar to the idea that CRād animals/people may have less muscle tissue and bone density, yet the quality of the tissue is higher, so you end up with stronger muscles and bone per tissue weight.
Obviously some of this is conjecture, but thatās the general idea behind the notion that any muscle loss - especially transient loss - as a result of calorie deficit is a net gain longer term. YMMV.
Bicep
#985
I bought both empag and dapag and am having trouble using up the empag. It makes me pee a lot and itās annoying. I even have to get up at night which I donāt otherwise have to do. Dapag is basically like taking nothing at all, I donāt even notice. The Dapag is gone and I wish I hadnāt bought so much empag.
Itās interesting that the two drugs have such a different effect on you. I thought all the sglt2 drugs caused increased urineā¦ and yes it is an issue with sleep. Have you checked your blood glucose, and do both drugs have an equivalent effect?
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Right. Peeing is how the body gets rid of the glucose mediated by the SGLT2i drug. If both empag and dapa get rid of the same amount of glucose, but you pee more frequently on empag, then it can mean that somehow either dapa concentrates more glucose in urine, so you pee less frequently, but get rid of more glucose in the same volume, or you on dapa you āsave upā more urine before peeing and so you can pee less frequently.
Of course itās also possible that you get rid of more glucose on empag than dapa, but I thought that all SGLT2i drugs were more or less equally effective in this regard. Unless of course you have a different individual response to these drugs. In any case as RapAdmin says, it would be interesting to find out which case it is.
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Bicep
#988
I went a couple months trying to figure that out and never bothered to go over the numbers because Iām such a spaz when it comes to checking blood glucose first thing in the morning. I always start my routine and forget. I had, over the course of a month 13 days of control (nothing) and 9 days of empag. Averages were 91.2 to 82.3 so it shaved off about 9 points. I wrote down thanksgiving dinner and when I took Rapa and ignored it. Kinda averaged out, both raised BG a little but randomly some were control and some were e. I would conclude empag works.
Huge surprise here. I tried to go the full 2 weeks control to see how Rapa affects BG. Then do a full 2 weeks dapag. Iām such a spaz. I got 22 numbers of control because I forgot to take the drug a bunch of times and remembered to test. Only got 7 of the Dapag. Control was 89.1 Dapag was 91.1. So it raised my BG. Obviously I was unhappy with these numbers and never looked at them again, but interesting anyway I guess.
BTW it was e25mg. and Dapag (forxiga)10mg. I donāt know what the equivalent is. Interesting, Iām surprised how it came out. I wouldnāt put too much faith in this study. Done by me. Lol.
Neo
#989
Thanks [quote=āadssx, post:981, topic:91ā]
See also: Effect of sodium-glucose transporter 2 inhibitors on sarcopenia in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
[/quote]
Just calling out the summary for people who did not look at the paper
Perhaps one does want to continue with SGLTi late in life, while they are great earlier in life
Anyone just good to have as part of the emerging data understanding
Conclusions: As one of the most widely used hypoglycemic, SGLT2 inhibitors have beneficial effects on FM and BW weight loss in T2DM, such as BW, BMI, WC, FM, PBF, VFA, and SFA. However, the negative influence on muscle mass paralleled the reduction in FM and BW, and the consequent increased risk of sarcopenia warrants high attention, especially as patients are already predisposed to physical frailty
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adssx
#990
Comparisons of the risks of new-onset prostate cancer in type 2 diabetes mellitus between SGLT2I and DPP4I users: a population-based cohort study 2024
Over a follow-up duration of 5.61 years, SGLT2I was associated with lower prostate cancer risks (HR: 0.45; 95% CI: 0.30-0.70) than DPP4I after adjustments. The subgroup analyses showed that the interactions between SGLT2I and age, hypertension, heart failure, and GLP-1a were not statistically significant. The result remained consistent in the sensitivity analysis.
SGLT2i never see cease to amazeā¦
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Might the sarcopenia or muscle loss in general be mediated by the loss of glucose and not enough getting into muscles? If itās just a loss of associated calories, then upping calories slightly, plus resistance exercise (this in any case should be standard for most, especially the elderly) should fix that. Unless something else is going on that is specific to SGLT2i class of drugs.
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Davin8r
#992
This is the million dollar question (for both SGLT2 and GLP drugs) to which I think weāre all waiting for the answer. Do they enhance sarcopenia through a mechanism that is independent of energy balance?
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raps
#993
where are people in the US getting their (off label) SGLT-2 inhibitors from? I see the following options:
- push health (or equivalent) for Rx + bexagliflozin from costplusdrugs.com for $50/month
- importing from india. people seem to be getting empagliflozin and dapagliflozin? as I havenāt imported any meds from india, somewhat worried about QC and shipping/storage temperatures.
any other options I mightāve missed? would also appreciate any data or anecdata on bexagliflozin vs other SGLT-2 inhibitors! I see a few drug comparison studies between the older inhibitors, but nothing on bexagliflozin specifically.
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Davin8r
#994
The good thing about empagliflozin from India is that you can get actual branded Jardiance for cheap instead of a generic, but you canāt get branded dapa. It comes in individual vacuum sealed moisture-proof foil blister packs.
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I think you have covered it pretty well. The issue with US purchasing is the appropriate $600/ month cost vs. $60 per month cost from India.
AgelessRX may offer it soon, check their website.
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Neo
#996
Can you ask that tomorrow in the PEARL webinar if you get the opportunity?
- if they will be sharing the data of their mini Cana trials soon
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A CGM would automate data collection so you donāt have build the habit of testing on a schedule and wonāt have to feel guilty about forgetting. I like to automate as much data collection as possible so I can keep my limited cognitive bandwidth avaliable for habits that cannot be automated.
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Bicep
#998
I agree the technology is almost there. I did get a Dexcom for a while, but was keto at the time and it was pretty boring and I didnāt think it agreed very well with my finger stick.
When Iām not busy I can handle it, but I used to deal with the chaos much better. Now my stack is not as deep and I lose the low priority stuff.
adssx
#999
Effect of SGLT-2 inhibitors on acute kidney injury in patients with heart failure: a systematic review and meta-analysis 2024
Our analysis included 25,172 patients with HF from 16 randomized controlled trials. Treatment with SGLT-2 inhibitors led to a 28% reduction in the risk of AKI progression compared to placebo (RR 0.72, 95% CI 0.61ā0.85, p<0.0001), without an increased risk of hypotension (RR 1.21, 95% CI 0.87ā1.70, p = 0.26) and hypovolemia (RR 2.26, 95% CI: 0.70ā7.33, p = 0.17). Notably, SGLT-2 inhibitors significantly decreased AKI in specific subgroups, including patients with HF with reduced ejection fraction (RR 0.59, 95% CI 0.43ā0.80, p = 0.0007), those treated with empagliflozin (RR 0.70, 95% CI 0.57ā0.88, p = 0.002) or dapagliflozin (RR 0.74, 95% CI 0.57ā0.98, p = 0.04), in studies with a follow-up of at least 1 year (RR 0.67, 95% CI 0.55ā0.82, p = 0.0001), and in patients aged 65 years or older (RR 0.72, 95% CI 0.61ā0.85, p < 0.0001).
Risk of dementia after initiation of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in adults aged 40-69 years with type 2 diabetes: population based cohort study 2024
110 885 propensity score matched pairs of initiators of an SGLT-2 inhibitor or a DPP-4 inhibitor were followed-up for a mean 670 (standard deviation 650) days, generating 1172 people with newly diagnosed dementia: incidence rate 0.22 per 100 person years in initiators of SGLT-2 inhibitors and 0.35 per 100 person years in initiators of DPP-4 inhibitors, with hazard ratios of 0.65 (95% CI 0.58 to 0.73) for dementia, 0.54 (0.46 to 0.63) for dementia requiring drugs, 0.61 (0.53 to 0.69) for Alzheimerās disease, and 0.48 (0.33 to 0.70) for vascular dementia. The hazard ratios for the control outcomes were 2.67 (2.57 to 2.77) for genital infections, 0.97 (0.95 to 0.98) for osteoarthritis related encounters, and 0.92 (0.89 to 0.96) for cataract surgery. When calibrated for residual confounding measured by cataract surgery, the hazard ratio for dementia was 0.70 (0.62 to 0.80). The association was greater for more than two years of treatment (hazard ratio of dementia 0.57, 95% CI 0.46 to 0.70) than for two years or less (0.52, 0.41 to 0.66) and persisted across subgroups.
SGLT-2 inhibitors might prevent dementia, providing greater benefits with longer treatment. As this study was observational and therefore prone to residual confounding and informative censoring, the effect size could have been overestimated. Randomised controlled trials are needed to confirm these findings.
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Has anyone tried the Glifozenix version of Canagliflozin available from India?
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mchasemd
#1001
Due to the cost of the gliflozins in the US, I resorted to remogliflozin out of India. I take 100mg twice daily at a cost (with shipping) at ~37 cents per dose. It dropped my fasting BS by about 20 and my post-prandial by ~40 mg/dl. I have no discernable side effects except increased urination. Iāve been on it for several months. It is not marketed in the US because it has a shorter half-life requiring twice daily dosing. Physicians always prefer a once daily dosing schedule and so it was a non-starter for the US. I am happy with it (and I started it for one reason only-- to get my BS lower when metformin and strict dieting were insufficient).
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Davin8r
#1002
Since you ordered from India, why not order a once daily (and better studied) drug such as branded Jardiance (empagliflozin)?
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Wolf has actually even done a study with Brad at Bradās lab. I think he was talking about it on a recent Stronger by Science podcast but memory fails.
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