#976

New study fresh off the press showing that tirzepatide virtually eliminated progression from pre-diabetes to diabetes (by 94%!!!). Also reduced blood pressure and average weight loss was 20%

Of course, it’s also a lot more expensive than dapagliflozin and requires a weekly injection.

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#977

Thanks, Davin8r. Unfortunately, while it looks like a great drug, it has the same practical obstacles like PCSK9i, too expensive for out of pocket, not approved for me by insurance, and not available through Indian pharmacies (and being an injectable, tricky in mail delivery).

So for now, SGLT2i it is, especially that there is some support based on ITP results.

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#978

SGLT2 inhibitors for patients with type 2 diabetes mellitus after myocardial infarction: a nationwide observation registry study from SWEDEHEART

The primary outcome measure was a composite of death and first hospitalisation for heart failure after one year analysed using an adjusted Cox regression.
SGLT2 inhibitor use was associated with lower rates of the composite outcome (hazard ratio (HR) of 0.70 (95% confidence interval (CI) 0.59–0.82).

Also, more and more papers suggest that metformin should be abandoned as a first-line treatment for diabetes and replaced with SGLT2i and/or GLP-1RA: [Drug therapy of type-2-diabetes-is metformin dispensable now?] - PubMed

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#979

I was reading with interest but weight loss to me would be a major drawback, since I struggle not to go catabolic.

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#980

It will be interesting to see more research on the GLP/SGLT2 drugs and body composition. I’ve been doing low dose tirzepatide to lose body fat, and it’s worked extremely well (hello 6-pack!) BUT I do think I’ve lost some lean mass despite my best efforts of protein intake and resistance training. I’m getting a DEXA body comp scan Tuesday to find out exactly what the changes have been.

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#981

Let us know the results, I’m very interested in this.

Regarding SGLT2, apparently they reduce muscle mass but they lower fat more so the fat % improves: Effect of SGLT-2 inhibitors on body composition in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials 2022

18 studies with 1430 participants were eligible for the meta-analysis. SGLT-2 inhibitors significantly reduced body weight(WMD:-2. 73kg, 95%CI: -3. 32 to -2. 13, p<0. 00001), body mass index(WMD:-1. 13kg/m2, 95%CI: -1. 77 to -0. 50, p = 0. 0005), waist circumference(WMD:-2. 20cm, 95%CI: -3. 81 to -0. 58, p = 0. 008), visceral fat area(MD:-14. 79cm2, 95%CI: -24. 65 to -4. 93, p = 0. 003), subcutaneous fat area(WMD:-23. 27cm2, 95% CI:-46. 44 to -0. 11, P = 0. 05), fat mass(WMD:-1. 16kg, 95%CI: -2. 01 to -0. 31, p = 0. 008), percentage body fat(WMD:-1. 50%, 95%CI:-2. 12 to -0. 87, P<0. 00001), lean mass(WMD:-0. 76kg, 95%CI:-1. 53 to 0. 01, P = 0. 05) and skeletal muscle mass(WMD:-1. 01kg, 95%CI:-1. 91 to -0. 11, P = 0. 03).

See also: Effect of sodium-glucose transporter 2 inhibitors on sarcopenia in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

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Parkinson's disease
#982

When you’re on negative calories, you almost always lose a bit of lean muscle. Unless you are using anabolics/testosterone or have just started gym training. Experienced natural ”bodybuilders” always lose a little muscle mass with diet.

So could this be largely due to the caloric deficit?

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#983

Hopefully! I was just hoping I could hold onto all the good stuff :grin:. I’m sure the pro bodybuilders are experimenting with GLPs during their cutting phases to make them less miserable, so I wonder what their experience has been?

#984

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 Longo’s 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 you’ve 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 that’s 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. It’s similar to the idea that CR’d 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 that’s 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.

#985

I bought both empag and dapag and am having trouble using up the empag. It makes me pee a lot and it’s annoying. I even have to get up at night which I don’t otherwise have to do. Dapag is basically like taking nothing at all, I don’t even notice. The Dapag is gone and I wish I hadn’t bought so much empag.

#986

It’s interesting that the two drugs have such a different effect on you. I thought all the sglt2 drugs caused increased urine… 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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#987

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 “save up” more urine before peeing and so you can pee less frequently.

Of course it’s 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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#988

I went a couple months trying to figure that out and never bothered to go over the numbers because I’m 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. I’m 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 don’t know what the equivalent is. Interesting, I’m surprised how it came out. I wouldn’t put too much faith in this study. Done by me. Lol.

#989

Thanks [quote=“adssx, post:981, topic:91”]
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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#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 amaze…

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#991

Might the sarcopenia or muscle loss in general be mediated by the loss of glucose and not enough getting into muscles? If it’s 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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#992

This is the million dollar question (for both SGLT2 and GLP drugs) to which I think we’re all waiting for the answer. Do they enhance sarcopenia through a mechanism that is independent of energy balance?

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#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 haven’t imported any meds from india, somewhat worried about QC and shipping/storage temperatures.

any other options I might’ve 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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#994

The good thing about empagliflozin from India is that you can get actual branded Jardiance for cheap instead of a generic, but you can’t get branded dapa. It comes in individual vacuum sealed moisture-proof foil blister packs.

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#995

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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