GLP-1 Drugs Don't Fix Everything

[hexagonal]

The good news is that even if you lost a lot of muscle while dieting down, getting it back is significantly easier than gaining it the first time.

There's still some debate on all the specific mechanisms around it (Satellite cells being deposited and sticking around being one of the leading theories), but the evidence is pretty conclusive that there's 'muscle memory' and significantly less stimulus and time is necessary to get back to prior levels of musculature than getting to new levels, even after years.

 

[keangkong]

The good news is that even if you lost a lot of muscle while dieting down, getting it back is significantly easier than gaining it the first time.

There's still some debate on all the specific mechanisms around it (Satellite cells being deposited and sticking around being one of the leading theories), but the evidence is pretty conclusive that there's 'muscle memory' and significantly less stimulus and time is necessary to get back to prior levels of musculature than getting to new levels, even after years.

I checked out whether the optimistic things you wrote squared with what I could find on Google Scholar. You're right. Sharples, et al. (2023). Skeletal Muscle Memory. J. Physiology - Cell Physiology 324(6), C1274-C1294, https://journals.physiology.org/doi..._content=0131b804-c9c3-4fca-bc54-1db9e51f9fd0.

 

[YoYoFat]

The good news is that even if you lost a lot of muscle while dieting down, getting it back is significantly easier than gaining it the first time.

There's still some debate on all the specific mechanisms around it (Satellite cells being deposited and sticking around being one of the leading theories), but the evidence is pretty conclusive that there's 'muscle memory' and significantly less stimulus and time is necessary to get back to prior levels of musculature than getting to new levels, even after years.

I was just talking to a colleague about this who used the very same language. Is dat yoooouuuu???

 

[hexagonal]

I was just talking to a colleague about this who used the very same language. Is dat yoooouuuu???

I basically only talk about this stuff on the internet and with my friends who I lift with, so I don't think so!

Unless you were in my garage gym a couple of hours ago.

 

[ProfPep]

There have been a variety of scholarly articles extolling the virtues of GLP-1 drugs for treating a variety of ailments other than just diabetes and weight loss. Here is a rare negative article on GLP-1 drugs. It concludes that while people lose weight on GLP-1 drugs, their aerobic fitness appears not to improve.

Liu, et al. (2025). Incretin Receptor Agonism, Fat-free Mass, and Cardiorespiratory Fitness - A Narrative Review. J. Clin. Endocrinology & Metabolism 110(10), 2709-2717 .

My aerobic fitness is down considerably in 10 weeks since starting, despite losing 20 lbs. This is because my exercise drive is down and resulting cardio down from 8 to 4hr per week.

Trying to reverse this trend with more structured training while staying on reta right now. Last two weeks aerobic fitness is going up.

There is NO SUBSTITUTE for exercise when it comes to aerobic fitness. (OK maybe daprodustat and related HIF activators, but not going there).

 

[keangkong]

My aerobic fitness is down considerably in 10 weeks since starting, despite losing 20 lbs. This is because my exercise drive is down and resulting cardio down from 8 to 4hr per week.

Trying to reverse this trend with more structured training while staying on reta right now. Last two weeks aerobic fitness is going up.

There is NO SUBSTITUTE for exercise when it comes to aerobic fitness. (OK maybe daprodustat and related HIF activators, but not going there).

Nice to hear your aerobic fitness has been going up for the last two weeks.

 

[ProfPep]

N

Nice to hear your aerobic fitness has been going up for the last two weeks.

I want to get it back to pre-reta steady state fitness level and then do some SS-31/MOTS-C/NAD research. I should be able to accurately quantify any benefits across a power duration curve.

Creatine has been the most obviously beneficial intervention to date. After a 3 year plateau, 5 days of loading at 25g/day increased max 60 second power by 12%, and weight by 2.5%. 9.50 vs 10.53 W/kg in 5 days. Increased anaerobic capacity by about 6kJ, which is a crazy intervention. Zero benefit to aerobic capacity tho.

 

[TooBigtoFail]

I have lost over 80 lbs with 0 exercise. If 20-30% is muscle loss, that's fine. I do not need those muscles anymore. I can run 7 flight of stairs with my heart only going up 10-15 bpm and not get out of breath ( which I could not do before). I can still lift over 120lbs of concrete bags or sand (with no back pain). I have not noticed any chores where I feel my muscles are not up to par. The day I cannot keep my balance on a 2X12 I beam, or push a 300+ lbs wheelbarrow, then I may exercise. I am retired and over 65. I just don't see the hype about muscle mass loss so far. I am more worried about the flappy skin.... I can't wait for a Dexa scan. Please don't listen to me.

 

[desinr-gal]

I have lost over 80 lbs with 0 exercise. If 20-30% is muscle loss, that's fine. I do not need those muscles anymore. I can run 7 flight of stairs with my heart only going up 10-15 bpm and not get out of breath ( which I could not do before). I can still lift over 120lbs of concrete bags or sand (with no back pain). I have not noticed any chores where I feel my muscles are not up to par. The day I cannot keep my balance on a 2X12 I beam, or push a 300+ lbs wheelbarrow, then I may exercise. I am retired and over 65. I just don't see the hype about muscle mass loss so far. I am more worried about the flappy skin.... I can't wait for a Dexa scan. Please don't listen to me.

TBTF, if you know that you can do those things you mentioned, then you must be doing those things, which are strenuous, and for most people would be considered physical resistance training and exercise! For you maybe not.. but clearly you are maintaining a sizeable muscle mass.

 

[keangkong]

I have lost over 80 lbs with 0 exercise. If 20-30% is muscle loss, that's fine. I do not need those muscles anymore. I can run 7 flight of stairs with my heart only going up 10-15 bpm and not get out of breath ( which I could not do before). I can still lift over 120lbs of concrete bags or sand (with no back pain). I have not noticed any chores where I feel my muscles are not up to par. The day I cannot keep my balance on a 2X12 I beam, or push a 300+ lbs wheelbarrow, then I may exercise. I am retired and over 65. I just don't see the hype about muscle mass loss so far. I am more worried about the flappy skin.... I can't wait for a Dexa scan. Please don't listen to me.

I am listening to you, however, from what you describe, you have plenty of strength.

 

[Fisherman2356]

I've used Reta to help lose over 80 lbs, and according to my scans, during the Reta phase of my cut, I actually gained almost 6 lbs of lean muscle mass.

For the lazy ones (like me LOL) that don't like exercise I think doing HGH helps retain muscle mass. I had lost some muscle while on Tirze and Reta (together with losing fat) but after couple months on 3IU hgh five days a week it seems I gained it all back. Plus, I had also lost some strength and now I'm at par to where I was before GLP1's. The thing thou is it seems you lose less weight if you do HGH while doing GLP1's, that's at least my experience. Perhaps the upside to that is you losing less weight because you are not losing any muscle? Nevertheless it could be a good idea to start HGH after you have reached or are close to reaching your goal weight.

 

[50ShadesGreyMarket]

There have been a variety of scholarly articles extolling the virtues of GLP-1 drugs for treating a variety of ailments other than just diabetes and weight loss. Here is a rare negative article on GLP-1 drugs. It concludes that while people lose weight on GLP-1 drugs, their aerobic fitness appears not to improve.

Liu, et al. (2025). Incretin Receptor Agonism, Fat-free Mass, and Cardiorespiratory Fitness - A Narrative Review. J. Clin. Endocrinology & Metabolism 110(10), 2709-2717 .

This further supports the notion that there is no magical treatment that doesn’t require some effort on the part of the individual. If people aren’t willing to change their lifestyle, they will never achieve optimal health. Sure, you can become catabolic and lose a ton of fat, muscle and possibly bone density given enough time but if you want to fix your metabolism, increase strength and endurance which will lead to fewer ailments as you age, you have to increase nutrients and resistance training.

I’ve seen some insane cases where someone insisted GLP’s made their hair fall out, lead to skin problems, salivary stones, dental erosion, the list goes on - these are caused by choices, like not drinking enough water, not getting enough nutrient dense foods and refusing to Increase protein and build muscle. The body building community is doing great on these but they have a completely different approach. They use it as a supplement to a strict regimen, not a replacement for healthy choices.

 

[geoguy78]

I’ve seen some insane cases where someone insisted GLP’s made their hair fall out, lead to skin problems, salivary stones, dental erosion, the list goes on

It's amazing how starving yourself and using such a high dose of a glp that it causes nausea and vomiting will cause the effects of starvation and chronic vomiting

This is why I think people are way too fixated on "food noise" and dosing to the point where there's zero hunger or enjoyment from food at all. Yeah, it's great to shed fifteen pounds in a month, but your body's telling you that your tank is running critically low and you need to listen to it. Go eat!

 

[Zydeceltico]

It's amazing how starving yourself and using such a high dose of a glp that it causes nausea and vomiting will cause the effects of starvation and chronic vomiting

..... your body's telling you that your tank is running critically low and you need to listen to it. Go eat!

And our bodies are way more automatic than we give them credit for.....if one's body senses starvation conditions (which is an overstated way of saying too big of a calorie deficit), it will actually be counterproductive to not eat. Not if one desires healthy weight loss.

 

[TacoLifter420]

I lost 70 pounds over 8 months using tirzepatide. The whole time I lifted heavy 4 days a week and got stronger. I am on TRT too, I lost very little muscle if any. For me at 50, tirz and TRT has been the fountain of youth. Now im just fine tuning using a lean bulk, small cut protocol.

Resistance training is so important as we age.

 

[Chucky]

I lost 70 pounds over 8 months using tirzepatide. The whole time I lifted heavy 4 days a week and got stronger. I am on TRT too, I lost very little muscle if any. For me at 50, tirz and TRT has been the fountain of youth. Now im just fine tuning using a lean bulk, small cut protocol.

Resistance training is so important as we age.

That right there. As we get older, training should change to reflect different goals. In my late teens and early to mid 20's it was about moving weight and snatching kitty lol. In my 30's it was honestly just a half assed effort in the gym which eventually led to putting on a bunch of weight. Think my heaviest I was about 200kgs. I sit between 130-135kgs which is my happy place. Lowest was 115kgs and though felt a looked good, being around the 130kg mark felt right for me. Now I've just turned 50, it's more about longevity, especially after my recent cardiac arrest a couple of months back. I'm happy now just to grab a couple of kettlebells and do complexes and finish off with some cardio strength training.

As for the GLP-1s, I think a lot of people who first jump on it think it's the solution to weight loss instead of a tool. I find reta is great for the food noise, but PYY, GLP-1 stimulation and ghrelin suppression come from eating a high protein diet, intermittent fasting and spending quality time in the gym. If I ever come off it, I would like to think that I now have to mindset to stick to how I eat and train to maintain my weight.

 

[Fisherman2356]

130kg mark felt right for me

130kg felt right for you, what are you like 10 feet tall LOL dude.

 

[Chucky]

130kg felt right for you, what are you like 10 feet tall LOL dude.

I wish, if anything, I'm getting shorter lol. At 130kgs, I carry a little extra weight( heavier now as I've been recovering over the last couple of months) but feel healthier at that weight. Before my CA, I would have my check ups every 6 months with my GP and everything was fine. Even after my CA when an echo was done on my heart in hospital, the doctors said there was no scarring or any kind of any indication that I had a heart problem, the only way it would have been picked up is if a coronary angiogram was performed and were surprised I had no symptoms leading up to it. I was in the gym 6 days a week, strength training, cardio training with kettlebells, steel maces and jumping into cardio classes a couple of times a week. I've always been a heavier guy and put that down to my polynesian genes.