Weight-loss drug found to shrink muscle in mice, human cells

There are a lot of people here citing loss of muscle mass as a side effect of GLP-1s, when the reality is that weight loss almost always comes with muscle loss.

For me, that hasn't even been the case. I'm down 40lbs on a relatively low dose of Semaglutide and my muscle mass has moderately increased over the last 6 months. The hysteria over this is totally unfounded.

Likewise, I did (and continue to do) keto for the last 6 months and lost 50lbs. 3 Weeks ago I started Semaglutide while continuing to do keto and it's just made everything easier. I've lost another 10lbs in the 3 weeks, am logging all my meals and taking macro goals into account. What's better is that because I was already "fat-adapted" as they say in /r/keto, my body isn't starving in a caloric deficit. It's just burning more fat as ketones.

Yes, I am trying to hit 100-150g+ of protein per day, yes I am in a caloric deficit. No, I don't feel like I have lost any muscle mass, but I do feel a lot more active at 60lbs lighter.

Yeah I've always found that complaint confusing. Of course you lose muscle when you eat less food. It'd be weird if that didn't happen. (Assuming you don't train hard or take hormones)

Yep. I started resistance training 5x a week about a month in on tirzepatide and even with a severely restricted caloric intake (I just can't eat enough), I've gained LBM.

How did you measure the increase in LBM? This requires very advanced technical equipment. My suspicion is that you have noticed an increase in muscle volume and assumed it to be an increase in muscle mass. Those are largely due to water retention and increased blood flow. They revert quite quickly after you stop exercising for about a week.

It predicts long term consequences on health. Not immediate ones. You wouldn't have noticed at all. Unless you measured your heart muscle weight.

It's good to work out. Perhaps it offsets any loss.

I get that it's upsetting and might contradict what you think.

At this stage we don't know for sure. It's something you might want to keep in mind. Especially if you take this drug without working out.

DEXA scans are accurate and readily available in most cities for about $100. Just do it quarterly or whatever.

I am getting regular DEXA scans

If someone is taking this medication for the right reasons, the risks of taking it are far lower than those associated with obesity and diabetes.

Also, concern of losing muscle mass on GLP-1 agonists (and diets in general) is well known and typically explained by the responsible MD to the patient.

You did not lose 40 pounds of fat while building lean muscle tissue unless you're BOTH relatively new to weightlifting and use PEDs, in which case, the "hysteria" is justified for an average person.

Just the former is likely enough over a 6 month span, even without great genetics. That's only a 1.6lb/week loss. Noob gains can be huge.

A caloric deficit that allows a continuous weight loss of 1.6 lbs a week for 6 months is significant enough to completely wreck your hormonal profile and put you in constant catabolic state, I doubt you would be able to put on any noticeable amount of muscle mass even during your noob gains phase in that context.

I've seen it happen with people even prior to the GLP-1s - prior to an injury derailing my last attempt to lose weight, I lost 30lb at an even faster rate and had 3 DEXA scans showing consistent increases in LBM.

This conversation does make me wonder about whether or not it would make sense to make the option available for people to go on exogenous testosterone (and yes potentially even women) while on these to help prevent muscle loss.

Does ability to lift weight also decrease in about a week? I was recently out of town for over two weeks and came back with the ability to lift roughly the same amount I was able to prior to leaving.

My DEXA scans seem roughly correlated with the amount of weight I can do in my regular sets, which has increased about 50-70% depending on which muscle group you are talking about.

This is with heavy resistance training 3 times a week and Pilates once a week.

A good portion of the strength related to any specific lift is CNS adaptation up until a certain point (and most new lifters won't hit that threshold for quite some time), so strength on a lift you've been doing regularly isn't necessarily a good indicator. Building muscle will of course increase your strength too, but I've doubled my squat since getting back into lifting while certainly not doubling the muscle mass of the respective muscles.

Fair enough. I didn’t mean a 1:1 correlation in 50% on a Dexa means 50% more strength, just would expect my lifting ability to go down if I lost muscle mass (or if it were water weight to begin with). Neither have decreased much if at all during breaks, so I’m fairly convinced it’s “real” so to speak.

Looking through my weightlifting app my best tracked exercise (leg press) increased about 250% from start with a 60% (roughly, speaking from memory) increase in lean muscle mass as measured by a DEXA scan. If I remember when back from dog walks tonight I’ll update that with a real number off the actual data.

I was a total newb at lifting though, so those early gains came quite quickly.

I am curious as this is a concern I have for long term health.

Studies show strength training while losing weight can retain almost 100% of muscle.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5946208/

Anecdotes don't equal data. "Always" and "never" don't exist in medicine. I'm sure that your experience is accurate to yourself, but these studies have to cast a wider net since there is always variability in results.

> low dose of Semaglutide

I thought its only approved at standard dose.

Your sample size is one. Imagine how a study saying this would get picked apart if their sample size was one. You have no idea whether you're in the middle of the normal distribution bell curve or at one of the extreme ends.

Anecdotally, it takes far less strength training than one would expect, too, to maintain muscle mass. From what I've experienced, 30 minutes a week, given sufficient stimulus, is enough.

There are more and more PhD researchers focusing on resistance training these days, and yeah, it turns out the minimum effective dose is waaaaaay lower than we previously thought.

https://www.minimumdosetraining.com/ - free training program + links to a bunch of studies the author was involved in on this specific subject.

There is a dosing schedule for all the GLP-1s, with what is considered the minimal therapeutic dose being several times your initial dose.

However, a lot of people either see results on these initial doses, and plenty of people find them to be effective as maintenance doses.

I would be more concerned about the thyroid cancer when taking these drugs...

https://scholar.google.com/scholar?as_ylo=2024&q=glp+1+thyro...

The two meta-analysis are interesting, I think.

https://www.liebertpub.com/doi/abs/10.1089/thy.2023.0530

> Overall there is no conclusive evidence of elevated thyroid cancer risk.

https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/do...

> Our meta-analysis showed that GLP-1RA treatment could be associated with a moderate increase in relative risk for thyroid cancer in clinical trials, with a small increase in absolute risk. Studies of longer duration are required to assess the clinical implications of this finding.

It's potentially a possibility, but the absolute risk seems to still be quite low.

I took it for a bit as a non-overweight person and the minimum dose was absolutely enough for me to have a hard time eating enough to maintain my weight.

I love this so much, thanks for sharing. I have my own minimum effective dose protocols that I use when life is kicking me in the face but I am going to try these on for size during the coming holiday season.

The post you are replying to didn't say "always" it said "almost always," wich is perfectly cromulent. And it's also consistent with all the literature I have seen too.

Meanwhile I’ve been on ozempic since 2021 and have lost significant muscle mass despite gaining 50 pounds (the drug helps with my diabetes but does nothing to my appetite).