From the article: "...explains this rate of muscle decline is significantly higher than what is typically observed with calorie-reduced diets or normal aging and could lead to a host of long-term health issues..."

The warning isn't that you're losing muscle during weight-loss with these drugs. It's that the ratio of muscle vs fat loss is much greater with the drugs compared to traditional weight loss methods.

It's been well studied that if you exercise and eat enough protein while losing weight, you can retain more muscle.

Losing a lot of lean mass is incredibly detrimental to your longevity and quality of life.

> Our bodies are really good at providing exactly the amount of muscle we need for our daily activities

The problem is that the average joe's daily activity is incompatible with an healthy muscle mass. After 30 if you don't actively exercise you lose muscle mass, if you're obese, 50 and starve yourself or take drugs that make you lose more muscles than necessary you won't gain them back ever unless you do some form of serious resistance training

https://hips.hearstapps.com/hmg-prod/images/triathlete-aging...

I'm not qualified to interpret results, but this paragraph stuck out to me:

> Using mice for the study, the researchers found that heart muscle also decreased in both obese and lean mice. The systemic effect observed in mice was then confirmed in cultured human heart cells.

So it also happened for already lean mice (though no mention of whether they still lost fat), and for cultured human heart cells (so not a by-product of needing less muscle to pump blood through a shrunken body).

> Our bodies are really good at providing exactly the amount of muscle we need for our daily activities

That is exactly the risk. Our bodies are really good at it. But we are taking drugs that may change what our bodies do. Even a small bit of extra heart muscle loss may push as below where our bodies would have left us naturally. Is that dangerous? Are there people who need to worry about it? How do we know whether or not that should be a concern? It raises questions, and is worthy of discussion, even if we do land at answers that say it is an acceptable level of risk.

I wondered about exactly this.

The study is actually a published letter [1], and it doesn't appear to account for this. Science Direct even published a study about this in 2017 [2]:

> Weight loss, achieved through a calorie-reduced diet, decreases both fat and fat-free (or lean body) mass. In persons with normal weight, the contribution of fat-free mass loss often exceeds 35% of total weight loss, and weight regain promotes relatively more fat gain.

We already know how to reduce the effect of this, the person simply needs to increase exercise as the weight is lost in order to maintain lean muscle mass.

[1] https://www.sciencedirect.com/science/article/pii/S2452302X2...

[2] https://www.sciencedirect.com/science/article/pii/S216183132...

When you gain weight, you also increase the muscles needed to carry that weight around. If you see someone obese at the gym doing the leg press, you may be astonished at how strong their legs are. When you lose weight, you don't need that muscle anymore.

Anyone can put up impressive #s on a leg pres. Try the bench press instead. No one impressed by leg press.

In regard to the oft claim of obese people being stronger or more muscular, not really. Studies show that obese people carry only a tiny extra 'lean body mass' compared to non-obese people when matched for height, age, and gender, and much of this extra mass is organs, not muscle. Otherwise, the extra weight is just water. Sometimes it is even less because obesity impairs movement, leading to muscle loss due to inactivity.

If obese people seem strong it is because the fat reduces the range of movement for certain lifts like the squat and bench press, so it's possible for obese people to put up impressive numbers owing to having to move the weight less distance. Same for pushing movements, e.g. linemen, as being heavier means more kinetic energy, but this is not the same as being stronger in the sense of more muscle output. This is why obese people are not that impressive at arm curls or grip strength relative to weight, but wirey guys can curl a lot relative to weight or have a lot of grip strength. An obvious example of this is overweight women having worse grip strength compared to men; the extra fat does nothing.

I don't mean to target your comment specifically because it's obvious you know the difference, but I'm continually annoyed by the conflation of fat and muscle as "weight," even by medical professionals who should know better.

We should not be talking about losing "losing weight" as a substitute for saying "losing fat," which is what most people mean. Likewise, when people say they want to "gain weight", they almost always mean they want to "gain muscle."

Why does this matter? Trying to manage one's health or fitness as "weight" gives (most) people the wrong idea about what their weight number represents, and what to do to improve their level of fitness and dial in on the anatomically appropriate amount of body fat. As an example, it's possible (although admittedly unlikely) for one to work hard to gain muscle and strength while reducing body fat and stay exactly the same weight the whole time. Their overall health, fitness, and longevity will be significantly improved but pop fitness will tell them that they haven't made any progress at all.

> When you gain weight, you also increase the muscles needed to carry that weight around.

I can't figure out how relevant that is. From what I've seen of obese people they always struggle with limited mobility, which often only improves with physiotherapy (or other forms of exercises). Sumo wrestlers are huge but can move faster than an equivalent obese person because (I assume) they have stronger muscles due to their regular regimented training and diet. Does this mean they have more muscle mass than fat compared to an equivalent obese person? Does more muscle mass indicate stronger muscles?

And obviously the heart is going to reduce muscle now that it doesn't need to pump blood through heaps of fat.

Then a study concentrates no comparing muscle weight loss by traditional dieting, that is a change in what someone eats, to weight loss via drugs.

It is not immediately clear if the muscle loss happens faster (probably) what the immediate impact of that is, and whether or not you lose more muscle mass on one or the other.

What they need is to design some sort of mouse gym.

I'm always so baffled by people commenting without reading the article first.

The percents are very different. For example in bodybuilding one normally 'bulks' while working out, because it maximizes muscle gain. But then naturally this needs to be paired with cutting, unless you're a Greek Grizzly, but the total muscle loss is relatively negligible, especially when maintaining a proper high protein diet.

At 40% muscle loss you're getting awful close to losing weight while increasing your body fat percent!

But of course you're right that diet+exercise is key but for those maintaining such, they wouldn't end up on these drugs to start with.

Whilst it is 95% calories in calories out, keto (not low carb, as low carb doesn't include high fat) can be good for muscle retention whilst in a defecit - as more foods that you consume naturally have higher protein (I utilise keto when looking to drop body fat, consuming a lot of slightly higher fat cuts of meat as a replacement for the carb calories, so chicken thighs instead of breast, 10% ground beef,etc). The higher fat content correlates to higher testosterone count, and higher protein means greater muscle retention.

To be clear, these recommendations are already made very clearly before you take the medication. There is absolutely nothing in your comment that isn’t already clearly spelled out. Your last paragraph is literally already being done.

This isn’t a surprise unless people ignored reading about the drugs before taking it and ignored the doctors.

It's why the medication should never be given to people on its own (although I'm sure it happens all the time), but should be a part of a comprehensive weight loss, exercise and dietary plan. Same with other invasive weight loss treatments, you can't just get a gastric belt or whatever fitted if you ask for it, you need to do the work yourself first, and you get a diet plan assigned if you do end up with one.

It's the same with e.g. human growth hormones, one theory is that Elon Musk is / has used them, but without the weight training that should go with it, so his body has developed really weirdly.

I've heard this feedback on Ozempic et al from my wife who is a GP some 6 months ago, when I mentioned how US is too much in comfort zone and addicted to HFCS to actually lose weight permanently, ever, so in good old weight-losing fads fashion they will just throw money at the problem, experiencing somewhat variable success and who knows what bad side effects.

My wife told me exactly this - potentially all muscle mass loss (and she made sure I understood that 'all' part), yoyo effect once stopping, potentially other nasty long term/permanent side effects, and overall just a bad idea, attacking the problem from a very wrong direction. Just look at musk for example - he pumps himself with it obsessively and the results even for richest of this world are... not much there (or maybe his OCD binging would make him 200kg otherwise so this is actually some success).

Then all the folks come who say how to helped them kickstart a positive change, like its something against those facts above. All the power to you, just don't ignore facts out there and don't let emotions steer your decisions. You only have 1 health and it doesn't recharge that much, and that short time we have on this pale blue dot is significantly more miserable and shorter with badly damaged health.

> (2g for every 1kg of body weight each day)

This equates to a 300lb male consuming 272g of protein per day. There are 139g of protein in 1lb of chicken breast.

The RDA to prevent deficiency for an average sedentary adult is 0.8 grams per kilogram of body weight. A 300lb male needs about 110g/day at this RDA.

For the people who lift weights while on this/these drugs, how much lean muscle do they lose?

The point is is that most people lose muscle because they’re not lifting. You will lose muscle if you lose weight no matter the cause, if you are not lifting weights.

On top of that wouldn't even liposuction already reduce heart muscle over time because of the lower amount of vasculature extent afterwards? Less volume to need to pump through and less metabolic and oxygen demand.

There is significant heart remodeling after even things like major amputations because of the changing demands on the heart.

Diet and exercise. It always comes back to that, yet people avoid it like the plague.

The modern weight loss program you described is pushed because that's what people want; an extremely low-effort methodology that yields extremely high results.

The idea that their is some silver bullet to weight loss has dominated the US health market for ages now because selling someone a pill that they don't have to do anything but swallow and be cured is really, really easy.

Having gone through my own weight loss journey, I have seen first hand how attractive that is and fell for it myself twice. So have loved ones, one whom is no longer the same person because they got gastric bypass which resulted in a massive change to gut and brain chemistry, something that we seem to be just figuring out is connected. My own journey is not over, but there are no longer any medications or supplements involved, because I can say with authority that none of them work without good nutrition and physical exercise.

As I realized this and just put more work into eating better and doing more activities (I did not join a gym, but started riding my bicycle more, walking neighbor's dogs, and doing body-weight exercises at home, etc, making it more integrated into my day rather than a separate event I could skip), I lost a healthy amount of weight and got stronger.

It took a lot longer, of course, than what the pills promised, but that's the trick of the whole weight loss industry...and make no mistake, it is an industry. Short-term results in exchange for your money. It was never about helping people be healthier and always about myopic profits, therefore we should not be trusting any claims these companies make that their silver bullet is the correct one, finally.

And yet.

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.

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

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

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.

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.

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.

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.

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...

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.

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).

> low dose of Semaglutide

I thought its only approved at standard dose.

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)

well it does lead to less eating so it indeed a side effect. if control group ate the same amount there would be no weight loss to begin with.

I tried taking it for IBS for that reason.

It worked! Kind of. The first few days after every dose it had the opposite intended effect so it wasn’t worth it.

A bare glp-1 agonist doesn’t, I think, but the weight loss versions are double-acting and do also slow digestion.

Another potential synergy for bodybuilding is that these GLP1 drugs ought to help maintain insulin sensitivity in the face of supraphysiological doses of HGH. Specifically I have the impression that tirzepatide and retrarutide are more effective here than semaglutide, as they possess additional mechanisms of aiding glucose disposal.

It says in the paper they used 21-week-old male C57BL/6 mice, as well as AC16 human immortalized cardiomyocytes

If you're trying to prove a positive benefit, then leaping from mice to humans is risky. If you're concerned about possible negative effects of something, then mice is a good place to start.

Yeah, I think caution is needed with a single study, especially with mice, when drawing conclusions about people.

However, this study is suggesting that semaglutide causes more muscle loss than would be expected based on calorie change alone, not just that weight loss is accompanied by muscle loss.

A lot of comments seem to be missing this critical part of the study.

I wouldn't be surprised if this doesn't replicate, but what they describe isn't quite what you might assume based on some of the comments in this thread.

I was also thinking if in used with testestrone, which is dangerous because the heart is a muscle and unintended consequence of trt is heart muscle growth which decreases blood flow.

This is a very thoroughly studied phenomenon. The hearts of obese people are generally more muscular as you say, but not in a good way, so I wouldn't compare this to training. In overweight people, the heart walls get thicker and the volume of blood that the heart pushes out with each stroke is decreased as a result. This means their heart needs to beat faster to reach the right throughput and their heart is under constant strain, kind of like having your car overrevved at all times.

With exercise, the heart muscles grow in a different way, and the volume of blood contained inside is not reduced. So without looking at the heart itself, we can't even tell whether a lot of muscle is good or bad, we also need to look at the rest of the context.

Interesting!

People do no realize how wide spread the GLP1 receptors are in the human body. GLPL1R is expressed on all muscles so heart muscle will be effected:

https://pmc.ncbi.nlm.nih.gov/articles/PMC5939638/

https://www.proteinatlas.org/ENSG00000112164-GLP1R/tissue

The way these drugs help loose weight is by increasing cellular activity by stimulating adenylyl cyclase and increased intracellular cAMP levels. It is not that hard and not a msytery to anyone who can think straight about human metabolism.

Tirzepatide let me stay away from the immediately appetizing junk food and almost exclusively eat a clean diet focused on protein.

My experience matches at least a dozen folks in my personal bubble. It’s sort of the point of the drug or it wouldn’t work very well.

Totally agreed on resistance training. The one thing I would change would have been starting that in a serious manner as soon I started the drug vs. waiting. Prescribing it is silly though - if that worked we wouldn’t need the drugs to begin with.

That may be your experience, it wasn't mine. I eat very healthy on Ozempic but yeah of the 60 lbs lost so far some of it is noticeably muscle because I don't exercise enough. The next 60 lbs of fat lost will hopefully be me swapping fat for muscle from weight lifting and swimming.

Going to add to the chorus here. One of the reasons these things are so successful is that it kind of kills the crave factor of eating. You don't get that feeling where you feel like you want to keep eating something addictive like pizza or fries just because it's there. It's why the packaged food companies are freaking out - all their work to engineer snacks where they can "bet you can't eat just one" is defeated by these, at least for now.

> When your appetite is crushed you don't go for the chicken breast, you go for what is immediately appetizing (usually carbs+fats like pizza or fries).

Um, when your appetite is "crushed", nothing is particularly appetizing. That is the entire point. It allows one to make better decisions or pass on eating.

I find it significantly easier to eat healthy on tirzepatide, fwiw.

That hasn't been my experience. I've been on liraglutide (Saxenda) for a month and a half or so and if I feel like I can't finish a plate of food I'll eat just the protein and leave the carbs, where I would've eaten everything before.

If found the opposite to be true.

I'm eating healthier than ever and don't care for junk foods anymore.

> a tax on unhealthy food to help fund Medicare and Medicaid.

Fully 13% of the population lives in an area with restricted access to grocery stores[1]. Couple that with car-centric anti-pedestrian development[2] and you have a definitively societal problem. Addressing that with taxes on the individual will not address these causes, only shift the burden further onto the poor.

1. https://www.aecf.org/blog/communities-with-limited-food-acce...

2. https://www.economist.com/finance-and-economics/2023/11/09/i...

> These drugs are turning into a band-aid on the fact that it's more profitable to sell addictive, high-calorie foods in the US than foods that promote long-term health.

The food is most of it, but it also doesn't help that our environments and society don't allow for as much mobility and exercise as our bodies evolved to expect. You can't force people to sit in a chair for 8-10+ hours a day staring at screens and then be surprised when a bunch of them are unhealthy. It's more profitable if you ignore people's health and keep them in place and working on task without interruption though so here we are.

given the low success rates of dieting, around 0 percent, gimmie the Band-Aid

> These drugs are turning into a band-aid on the fact that it's more profitable to sell addictive, high-calorie foods in the US than foods that promote long-term health.

What I don't understand about these drugs is:

Ok, you are taking the medicine to lose weight, but are you eating the same shit as before in the process?

The answer is always "pfft no, I am going to eat healthier"

So why don't you just eat healthier now?

There are non-steroidal OTC supplements that are specifically anti-catabolic instead of anabolic like HMB[1], a metabolite of the amino acid leucine, and also widely used in the fitness community. Personally I have no idea which is preferable though, or whether anti-catabolism is something actually positive, as we know the importance of autophagy of senescent cells for longevity. Most of the literature I read suggests the less growth signalling, the better longevity, with the only exception being the frail elderly.

[1] https://en.wikipedia.org/wiki/%CE%92-Hydroxy_%CE%B2-methylbu...

I have done exactly this. I stack semaglutide with ~ 1 ml testosterone and .35 ml of anavar weekly. I’ve transitioned out of regularly competing in powerlifting to running and yoga everyday. 47lbs down in 5 months and havent felt this good since college.

How are bodybuilders getting a phase 2 trial drug still in development by Lilly?

Add on that there is no complete understanding of this system with all the Unknown Unknowns etc and you can see why we should test this stuff better before letting hims.com just disperse it across the american populace

A computer is much more likely than your body to have small, self contained parts that just function. Your body is the result of millions of years of accidental evolution - See the canonical example of the laryngeal nerve in a giraffe. Computer programs are often designed to be small and modular. They might have to worry about memory layout shifting because some other program grew - That's nothing like your spleen trying to occupy the same physical space as your stomach and causing digestion issues.

For all of medical science's experience and history with debugging the human body, there's still so much more to understand.

I like the analogy that biologists are making code changes (especially with genetic therapies) without actually understanding the machine code specification or even having a copy of the source code.

It's like a hacker flipping bits in a binary trying to figure out what's going to happen.. except the hacker at least can look up the complete machine code.

Yea, except without error checking, and fully analog technology.

Although, "single cosmic ray upset events," are just as devastating.

Weight loss is not "off label" for this drug.

Well, in vitro.

> but we did not see increased heart disease in human RCTs of these drugs.

In fact, we've even seen the opposite - that it's cardioprotective.

They found the mice did not suffer from any heart problems, so it’s not surprising.