22 ms·

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

372 points by Eumenes 2y ago

polishdude20 2y ago
It seems the article isn't just saying it's heart muscle that's being lost but regular muscle in general. Even more so than in a low calorie diet.
- sfink 2y ago
  There's a linked article saying that 40% of the weight loss is muscle.
  - com2kid 2y ago
    Outside of cardiac muscle, which is a bit worrisome, 40% of weight loss being from muscles is incredibly typical for any diet that sheds pounds. There are very complex dietary regimes that can be followed to minimize this, but most studies have shown that they don't save any time compared to losing weight and then working to get the muscle back afterwards. > Dyck’s study comes on the heels of a commentary published in the November issue of The Lancet by an international team of researchers from the U of A, McMaster and Louisiana State University who examined emerging research showing that up to 40 per cent of the weight lost by people using weight-loss drugs is actually muscle. This is, again 100% typical of what happens with caloric restriction.
    - throwup238 2y ago
      Literally the next line after the 40% quote: > Carla Prado, a nutrition researcher in the Faculty of Agricultural, Life & Environmental Sciences and lead author on the commentary, 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 — including decreased immunity, increased risk of infections and poor wound healing. Do you have a source that 40% muscle loss is typical for a caloric restriction diet without GLP1 agonists?
      - com2kid 2y ago
        > Do you have a source that 40% muscle loss is typical for a caloric restriction diet without GLP1 agonists? OK I actually checked up on this, and it is more like 30%, but that number gets worse as you get older. For young healthy men it can be 20%, but as you get older that number gets worse and worse. I'd want to see a comparison of a similar cohort of people going on a calorie restricted diet of the same magnitude, with a similar (lack of) activity levels. The study at https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00272-9/abstract https://www.thelancet.com/journals/landia/article/PIIS2213-8... compares people who had less overall weight loss on a pure calorie restricting diet, which, well, by definition isn't the same thing.
    - loeg 2y ago
      > There are very complex dietary regimes that can be followed to minimize this The dietary regime isn't complex -- just consume a LOT of protein. Something like 1-2 g/kg/d. And non-dietary: do strength training.
      - devmor 2y ago
        Yep, I can anecdotally confirm as I’m on such a routine right now. I started losing weight from severe obesity with a caloric deficit but noticed I was also feeling weaker in general (aside from the tiredness that comes with eating under your TDEE). I started going to a trainer and he had me change my macros so that I was consuming about 200g of protein per day in addition to 4 days per week of full body workouts on top of my cardio. Since then I’ve lost an additional 150% of my initial weight loss, and have gained moderate muscle mass on top of that.
      - com2kid 2y ago
        This works until it doesn't. Professional body builders do bulk/cut/bulk/cut because after awhile you can't lose weight and put on muscle at the same time, especially if you want to get to the point of being shredded. (well you can do it, but there is no benefit over bulking and cutting)
        loeg 2y ago
        This comment is not responsive to mine. I am talking about minimizing muscle loss during weight loss, not losing weight and putting on muscle at the same time. And bodybuilders do exactly what I said during their cut phases -- to minimize muscle loss. (Most people losing weight on these drugs are not bodybuilders.)
- derektank 2y ago
  From the commentary, >Studies suggest muscle loss with these medications (as indicated by decreases in fat-free mass [FFM]) ranges from 25% to 39% of the total weight lost over 36–72 weeks. This substantial muscle loss can be largely attributed to the magnitude of weight loss, rather than by an independent effect of GLP-1 receptor agonists, although this hypothesis must be tested. By comparison, non-pharmacological caloric restriction studies with smaller magnitudes of weight loss result in 10–30% FFM losses. Comparing weight loss of different magnitudes is kind of comparing apples to oranges. Of course, it's not really possible to get persistent, large magnitude weight loss any other way than by using these drugs, so I understand why the comparison was made.
therein 2y ago
I like how they aren't saying Semaglutide in the title in an attempt to perhaps keep it from immediate scrutiny.
- neom 2y ago
  https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss https://www.fda.gov/drugs/postmarket-drug-safety-information... Same thing??
  - therein 2y ago
    > Unapproved GLP-1 Drugs Used for Weight Loss Yeah that would be perfect. But editorializing it to the point of calling it `weight loss drug`, just feels like it is begging for the reaction of "oh yet another weight loss drug".
  - TylerE 2y ago
    No. That’s talking about the compounded versions (NOT in an auto pen) that were temporarily allowed due to shortages, but whose authorization has since been revoked.
- rzzzt 2y ago
  The first link goes to the study and it does mention the ingredient: https://www.sciencedirect.com/science/article/pii/S2452302X24002869 https://www.sciencedirect.com/science/article/pii/S2452302X2...
  - therein 2y ago
    I am talking about UAlberta's title specifically.
    - rzzzt 2y ago
      "Semaglutide Reduces Cardiomyocyte Size and Cardiac Mass in Lean and Obese Mice" was also written by UoA researchers. I don't see anything nefarious in the choice of the title for the news blurb.
jongjong 2y ago
As a coder, I'm realising more and more that the human body isn't so different from a computer. When you try to fix something without having complete understanding of all the relevant parts of the system, you will invariably introduce new issues. With a machine as complex as the human body, it seems inevitable that the field of medicine would be a game of whac-a-mole. Finding solutions which don't create new problems is hard and should not be taken for granted.
- kylehotchkiss 2y ago
  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
  - jongjong 2y ago
    Yes 100%. That's why I never understood the rollout of MRNA vaccines during COVID. It's like pushing a massive code change straight to production during peak traffic and without the normal phased rollout. I totally understand where conspiracy theorists are coming from. That didn't seem right.
    - kylehotchkiss 2y ago
      yeah, it's too bad the tech didn't have a better way to gain peoples trust (through some other breakthrough with the normal set of clinical trials). I think the solve was impressive (tell cells to produce a protein that looks exactly the same as the viruses and place it outside the cell to piss off antibodies) but protein-protein interaction data is hard to come by. Maybe these guys can figure it out https://www.aalphabio.com https://www.aalphabio.com
    - _yb2s 2y ago
      It made sense to me- they made a risk vs benefit decision under high uncertainty, factoring in the massive harm that the ongoing pandemic was already causing. There had already been 12 years of human clinical trials for other mRNA vaccines, and they still did extensive clinical trials for the new covid vaccine before rolling it out. In hindsight they were exactly right- and they saved at least tens of million of lives by acting quickly[1]. [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC9537923/ https://pmc.ncbi.nlm.nih.gov/articles/PMC9537923/
wizzard0 2y ago
well that's a weight reduction too! on a more serious note, could it be that the load on the muscle gets lower so they adjust? 8% reduction for 30% body weight reduction sounds reasonable to me at first glance
cm2187 2y ago
> emerging research showing that up to 40 per cent of the weight lost by people using weight-loss drugs is actually muscle That's the sort of headlines that smells like bullshit to me. My understand of those drugs is that they don't actually make you lose weight, they just cut your appetite so you can follow a diet to lose weight without hunger hammering at the door. So to start with, if that's the case, all they are observing is the effect of a diet. Not sure the diet drug has much to do with it. Then I went from 133kg to 88kg with these diet drugs. Even though I exercised every day, I am sure I also lost some muscle mass as well, just because I don't have to carry 45kg every time I make a move anymore. Seems logical and would probably be concerned if it was any other way.
- taeric 2y ago
  Yeah, folks don't like thinking that obese people have a lot of muscle needed to move around. And losing weight is losing all weight.
- hnthrowaway0328 2y ago
  Just curious, does your appetite come back whence you cut off the meds? The only reason I want to lose weight is to eat more freely, won't be useful if I lose my appetite too.
  - 0xB31B1B 2y ago
    Appetite comes back yes
  - andreareina 2y ago
    It does.
  - xeromal 2y ago
    I saw someone mention that they craved heroin less on ozympic.
  - cm2187 2y ago
    You don't lose taste, you lose your appetite, which means you can resist the temptation to eat easily, and you feel full very quickly. That doesn't prevent you from eating what you like, but it does help you to not eat too much of it, which I hope is not what you mean by "more freely". The appetite comes back when you cut the meds, but it's an appetite based on your new weight. But if you then go on a some suggar rampage, you will regain weight and your appetite will grow too. Those drugs are merely a guard rail to complete a diet successfully, but if people do not change their eating habbits, the same causes will produce the same effects after they cut the meds.
PlunderBunny 2y ago
I like the way the title ends with "human cells" as if the main reason it was there was to cut off (?) all the people that respond with "In mice."
- loeg 2y ago
  Well, in vitro.
xyst 2y ago
folks, this is why I lean on skepticism in regards to “off label” usage (ie, weight loss). Have only lived a few decades on this planet and the weight loss trends with pharmaceuticals is wild.
- ahahahahah 2y ago
  Weight loss is not "off label" for this drug.
delichon 2y ago
It also decreases gut motility, which helps with the intended effect of appetite suppression. Young healthy people tend to shrug at that. As an old person that takes it right off the menu even before I read about accelerated sarcopenea. Maybe it's the same effect on the peristaltic muscles.
- vundercind 2y ago
  A bare glp-1 agonist doesn’t, I think, but the weight loss versions are double-acting and do also slow digestion.
  - loeg 2y ago
    Tirzepatide (Zepbound) is double-acting but semaglutide (Ozempic) isn't. Both are prescribed for weight loss.
- Auracle 2y ago
  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.
httpz 2y ago
Some of the side effects of semaglutide are just a result of eating less calories. Without a control group who also ate the same amount of calories but without the drug, it's hard to know if the side effect were directly caused by semaglutide or just a result of being in a calorie deficit.
- hackernewds 2y ago
  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.
renewiltord 2y ago
This is going to be a non-result. It won't matter. The win from losing weight will easily outclass all of this. This drug should be in wide circulation. When the patents expire, we will enter a new era of American health.
loeg 2y ago
So like, it's interesting that this happens in mice, but we did not see increased heart disease in human RCTs of these drugs. Maybe the mouse dose is just absurdly high? "Mice were then administered semaglutide 120 μg/kg/d for 21 days." That could be vaguely reasonable -- human doses range from, idk, ~36 to ~200 μg/kg/d (2.5mg/week to 15mg/week at ~100kg).
- 7e 2y ago
  They found the mice did not suffer from any heart problems, so it’s not surprising.
- cthalupa 2y ago
  > 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.
DidYaWipe 2y ago
So... could this be a treatment for enlarged hearts?
- FollowingTheDao 2y ago
  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://pmc.ncbi.nlm.nih.gov/articles/PMC5939638/ https://www.proteinatlas.org/ENSG00000112164-GLP1R/tissue 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.
LeoPanthera 2y ago
It's my understanding that if you have hypertension, your heart muscle grows thicker as a consequence of working harder against your blood pressure, which reduces the flow capacity of your heart. So if you have hypertension, this might actually be a "good" side-effect?
- rootsudo 2y ago
  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.
deleted 2y ago
[deleted]
akira2501 2y ago
The marketing is astounding. "Weight-loss drug." Oh, would that be Semaglutide? <click> Hey, would you look at that!
bastawhiz 2y ago
The research says > Together these data indicate that the reduction in cardiac size induced by semaglutide occurs independent of weight loss. Which does sound concerning. It's the drug, not the weight loss, that causes the muscle loss. I guess the question is whether it's better than nothing. Is the loss in lean muscle a worse outcome than remaining obese?
jyscao 2y ago
[flagged]
- vundercind 2y ago
  At the very least, we should expect to see the same kinds of downsides you’d see for anyone who managed to eat way, way less and lose weight at a multiple-pounds-per-week rate for weeks and weeks on end without taking a drug to do it. They’d be truly miraculous if they achieved their results without even the same cost as doing the same thing without the drug.
- monero-xmr 2y ago
  No one seems to remember Fen Phen or its stratospheric rise and fall https://en.m.wikipedia.org/wiki/Fenfluramine/phentermine https://en.m.wikipedia.org/wiki/Fenfluramine/phentermine
  - Someone1234 2y ago
    No one who brings up Fen Phen seems to grasp how long both that and GLP-1s have been on the market. We're up to 4x Fen Phen's run already (5-years Vs. 20-years). GLP-1 Agonists aren't new, they've just been approved for additional usages. So why, after 20-years, and millions of people haven't fen-phen-like side effects appeared?
  - MBCook 2y ago
    That was one of my first thoughts. It’s perfectly possible for a new hot to have a severe side effect that won’t be noticed for quite a long time. Semiglutide appears to have undergone final clinical trials in the US around 2017. Given it hasn’t been on the market terribly long and has only an exploded in popularity relatively recently it doesn’t seem like it would be that hard for it to have a serious side effect in a small portion of the population that hadn’t been detected before due to the limited number of people taking it, the amount of time it takes to manifest, or both. Obviously it’s providing significant benefit that risk could easily be worth it. But as it gets marketed towards more and more people that won’t be true for all of them.
oksurewhynot 2y ago
I thought this was known about older GLP-1 antagonists like semaglutide, which is why there's some excitement around the newer dual-action types like tirzepatide? My understanding is the newer drugs cause substantially less muscle mass loss.
CyanLite2 2y ago
If you’re 20% smaller, it would make sense that your heart could pump 20% less.
- dgfitz 2y ago
  Uh, I think most highly in/shape people have normal sized, very healthy hearts and their bpm is like 45. Their hearts are not physically smaller, nor did they shrink during their build-up to current physique. Saying things like this is harmful at best. Please don’t.
wileydragonfly 2y ago
Don’t care. I’m down 30lbs.
jmward01 2y ago
I wish discussions would focus on all source mortality instead of single stat x. If the all source mortality data comes back favorably you could read the interpretation of this data 100% opposite: regular calorie restricting diets fail to reduce heart size... Point being, without all source mortality data to back up that this is a bad thing it is a very hard stat to care about.
acyou 2y ago
The study found that heart muscle decreased in both lean and obese mice. So any observed muscle loss might not be just from losing body mass and not having to work as hard. But if you're already lean and then go on a calorie deficit (as a result of decreased appetite from taking the drug), then muscle mass will be lost through metabolism of muscle and other tissue. Then the study states further that the proportion of muscle loss is higher than expected from calorie restriction alone. My gut feeling here is that where there's smoke there's fire, and I predict dramatic class action 40 years in the making, either like tobacco, or like baby powder, depending on the actual long term health outcomes. And, this is great research! We need more like this ASAP!
- derbOac 2y ago
  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.
GenerWork 2y ago
I hope they re-run this study with retatrutide vs semaglutide. Apparently retatrutide does a better job at preserving muscle, and some bodybuilders will take small dosages (.5 - 1mg a week) of it in order to lose stubborn fat but keep muscle.
- loeg 2y ago
  How are bodybuilders getting a phase 2 trial drug still in development by Lilly?
  - cthalupa 2y ago
    China. It's trivial to purchase retatrutide, semaglutide, tirzepatide, and a wide variety of other peptides from Chinese labs, and for pennies on the dollar compared even to compounding pharmacy prices.
ramesh31 2y ago
>My understand of those drugs is that they don't actually make you lose weight, they just cut your appetite so you can follow a diet to lose weight without hunger hammering at the door. While acknowledging that the mechanism is different, this was the same effect of Ephedrine, which went through a similar craze as Ozempic before the full complications were known. My bet is that this will be similar, where the risks end up being outweighed by the benefit for extreme obesity and diabetics, but that the cosmetic weight loss aspect of it will become outlawed or highly regulated.
dyauspitr 2y ago
Sounds like a perfect counter to using steroids in bodybuilding which can cause an enlarged heart. I wonder if we will start seeing GLP-1 in bulk cut cycles more moving forward.
talkingtab 2y ago
It concerns me how discussions, such as this one go on HN. This is an important topic. With the epidemic of obesity we now find a drug that appeals to a large number of people. This is an important topic as well. What is the current comment receiving most of the comment? "That's the sort of headlines that smells like bullshit to me" That's the sort of comment that smells like bullshit to me. What kind of place is this? Many times I find the posts on HN interesting, but increasingly these kind of comments make me wonder about Y Combinator. Is this really the best they can do? And for us readers who are supposed to be so called hackers, is this the best we can do?
- throwaway2037 2y ago
  I agree 100%. Those kinds of comments have no place, and add little to nothing to the discussion. Many HN discussions outside of pure tech invite all kinds of crazy and uninformed comments -- health/diet, finance/economy, etc.
- elevatedastalt 2y ago
  The HN you are yearning for disappeared about 8-10 years ago when it was largely taken over by normies and people way outside the hard-core-tech fold. It's not very different from Reddit front-page now if the topic is even remotely political. For purely technical topics you expect good quality discussion, but those threads barely get comments in the two digits.
  - deleted 2y ago
    [deleted]
  - patrickhogan1 2y ago
    Yes sometimes the loudest voice definitely rises to the top and it’s annoying, but I also think it’s a condition that too many new members don’t know how to use the upvote button. I also think it’s a symptom that HN does not allow enough people to use the down vote button. you could be a commenting member for years and not be able to downvote or you could be somebody who posts a few click bate links you copied from another aggregator and all of a sudden you have the ability to downvote. It’s pretty dumb.
et2o 2y ago
This is most likely a good thing. It isn't killing cardiac myocytes, it's probably assisting with reverse remodeling. Fits with why we know it helps in heart failure.
quantumwoke 2y ago
Seems like some of the comments need to learn that a big hypertrophic heart is much worse for you than a normal sized heart. Folks: GLP-1s have demonstrated benefit from heart failure, and this heart muscle change is probably mechanistic in that.
7e 2y ago
“Dyck, who is the Canada Research Chair in Molecular Medicine and heads up the Cardiovascular Research Centre, says his team did not observe any detrimental functional effects in hearts of mice with smaller hearts and thus would not expect any overt health effects in humans.” This makes sense. If fasting hurt your heart many of your ancestors would have died early. There is strong selection pressure to survive extended fasts.
siliconc0w 2y ago
It's pretty clear that GLP-1 should be prescribed with protein powder. 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). IMO this and a lack of resistance training (which should also be prescribed) probably makes up a large % of the muscle loss on these drugs. The problem is that the FDA only looks at dumb measures like weight lost, not body fat % when approving these drugs.
- meragrin_ 2y ago
  > 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.
- cthalupa 2y ago
  I find it significantly easier to eat healthy on tirzepatide, fwiw.
- technofiend 2y ago
  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.
- phil21 2y ago
  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.
- jf22 2y ago
kbos87 2y ago
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.
- mgiampapa 2y ago
  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.
- NavinF 2y ago
  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)
- cthalupa 2y ago
  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.
  - xk_id 2y ago
    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.
mistercheph 2y ago
There is no way magic weight loss pill with no side effects could possibly go wrong!!!
robwwilliams 2y ago
Not a solid paper—-more like an abstract. I could not find any information on the strain or type of mice they studied. Data from one strain often fails to generalize to others. Trying to leap to human implications is beyond risky.
- insane_dreamer 2y ago
  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.
  - robwwilliams 2y ago
    Yes, you are right, but ideally a team should test several genetic backgrounds of mice. Almost all cancer treatments have some negative effects. It is crucial to know what genetic and exposure variables to avoid to maximize therapeutic benefits. Cadmium in some strains of mice is highly toxic to male testes. But if, as in the C57BL/6J strain, you have a “lucky” transporter mutation, then no problems at all. This kind of variability has been known since the turn A. Garrod in the early 1900s. And ignored by many. Here is the data on the cadmium example I just mentioned: https://genenetwork.org/show_trait?trait_id=13035&dataset=BXDPublish https://genenetwork.org/show_trait?trait_id=13035&dataset=BX...
- jr000 2y ago
  It says in the paper they used 21-week-old male C57BL/6 mice, as well as AC16 human immortalized cardiomyocytes
  - robwwilliams 2y ago
    Ah, thanks. I looked but not carefully enough! C57BL/6 – the canonical inbred fully homozygous mouse that unfortunately is used as the “HeLa cell” of almost all experimental murine biomedical research. I understand the reason this happened, but there is no excuse in 2024 to use just one genome (and an inbred one at that) to test translational relevance. Consider this work a pilot worth testing in NZO, DBA, A, C3H and BALB strains and some F1 hybrids. Whatever the results they should have good generality to mice in general.
tomhoward 2y ago
I'm not commenting specifically on the heart-muscle aspect of the study, but it shouldn't be a surprise that the weight loss from this drug is significantly attributable to muscle loss; it almost always is when dieting. It's the same with keto/low-carb or any other kind of caloric-restrictive dieting (which Ozempic facilitates). The modern weight-loss programs I'm seeing now (at least those aimed mostly at middle-aged men) emphasize consuming significant amounts of protein (2g for every 1kg of body weight each day) and engaging in regular resistance training, in order to maintain muscle mass. The article addresses this: To keep muscle strong while losing weight, Prado says it is essential to focus on two main things: nutrition and exercise. Proper nutrition means getting enough high-quality protein, essential vitamins and minerals, and other “muscle-building” nutrients. Sometimes, this can include protein supplements to make sure the body has what it needs. Perhaps there needs to be more formal research into this, and a strong recommendation made to everyone using these drugs that this kind of diet and exercise plan is vital.
- jjallen 2y ago
  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.
  - phil21 2y ago
    Not sure how much I lost during, but a substantial amount. I have been working out since about 20lbs from my goal weight and now roughly a year later - and have gained strength (based on the numbers I can lift) from before I lost 100lbs. I don’t think it would have been possible to not lose substantial muscle mass while rapidly losing 100lbs over 9mo, even with extreme resistance training added to the mix. While DEXA scans are not super accurate, I’ve put on about 17lbs of muscle since my first scan 10mo ago, while maintaining a 12% or less bodyfat ratio. That said, I’ve been eating extremely healthy both before and after being on the drug which helps a lot. The drug simply gave me the mental space to avoid the binges which were my particular problem. That and it controls portion sizes to European dinner vs. American restaurant sized meals for me.
diath 2y ago
The problem with appetite suppression drugs is that they simply make you not feel hungry, but do nothing to fix your lack of discipline and self-control, I'm sure most people who lose weight on these drugs, and then come off, will just go back to their bad habits.
- echoangle 2y ago
  So why not just stay on the drugs?
  - diath 2y ago
    You technically could but the idea here is to cut the excess bodyfat percent and get into the healthy range, rather than to keep losing weight, which itself is also unhealthy, but once you become dependent on the drugs to maintain your weight, without fixing your habits, you will just go between getting off the drug, binge eating, gaining the weight back, and hoping back on the drug and losing weight while barely eating, I can't imagine bouncing between such two extremities being good for your health.
    - echoangle 2y ago
      Can’t you just adjust the dosage to stabilize?
      - phil21 2y ago
        Yes, you can. Or most people can. It’s called a maintenance dose and is usually the minimum dose available for the particular drug you are on. As these become more common and doctors more aware, the dosing guidelines will become much more nuanced and dialed in.
    - cthalupa 2y ago
      Well, lots of people back off those dosages once they reach their goal weight and have minimal difficulty maintaining. As we know more about the long term effects of staying on the drug, it's totally possible it might make sense just to keep on it. But as someone who spent a good chunk of their early adulthood having no problem with healthy habits and then slowly slipping into tons of bad ones, getting on tirzepatide has made it as easy for me to make those healthy choices that I made when I was in my 20s. Ones that I struggled with mightily after I got fat. Hopefully more and more people will use them as a tool to help them get things back and order and then stay there, whether or not they keep taking it.
dukeofdoom 2y ago
If it causes cellular damage, it might be a big problem. "Some studies indicate that only about 1% of heart cells are renewed each year in younger people, dropping to about 0.5% by age 75. This means that a significant portion of heart cells remain from childhood into old age."
raverbashing 2y ago
Keyword: "in mice" Second gotcha: how much of the decrease is just attributed to the lower mass of the subject after the weigh-loss treatment Though it's one good reminder that "catabolism" and "anabolism" are less selective than we wished to
Anotheroneagain 2y ago
I've been warning people for a long time that the drug only fakes the signal of fullness from the gut, and only makes you starve yourself. It doesn't actually fix anything.
- deleted 2y ago
  [deleted]
heisenbit 2y ago
It may be worth considering that a heavier person needs a stronger heart than a lighter one. The heavier weight also acts as a constant load/training. Without some degree normalization we won‘t know whether this is normal or concerning.
- Etheryte 2y ago
  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.
  - ben7799 2y ago
    I think doctors can figure out real quick which version of heart enlargement you have. The athletes heart is going to beat at 1/2-1/3 the rate at rest compared to the obesity-enlarged heart and a stress test is going to show the athletes upper heart rate limits are much much higher.
    - Etheryte 2y ago
      This is pretty much exactly what I said?
lofaszvanitt 2y ago
Erm, when you lose weight you usually lose muscle too. So compared to people on a diet and people on ozempic, what's the plus percentage of muscle loss?
crazygringo 2y ago
I'm always so baffled by warnings about losing muscle when losing weight. Of course you do! If your body is tens of pounds lighter, then you don't need the extra muscle to lug it around. This paper is about reduction in heart muscle, and of course your heart doesn't need to be as strong because there's less blood to pump and less tissue to fuel. 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. Our bodies are really good at providing exactly the amount of muscle we need for our daily activities (provided we eat properly, i.e. sufficient protein), so it's entirely natural that our muscles decrease as we lose weight, the same way they increased when we gain weight. Muscles are expensive to keep around when we don't need them. Obviously, if you exercise, then you'll keep the muscles you need for exercising. But this notion that weight loss can somehow be a negative because you'll lose muscle too, I don't know where it came from. Yes you can lose muscle, but you never would have had that muscle in the first place if you hadn't been overweight -- so it's not something to worry about.
- antihero 2y ago
  What they need is to design some sort of mouse gym.
  - zenomadic 2y ago
    MouseLifts 5x5 + RAtkins diet
    - gonzo 2y ago
      "Gym rats" was already a thing.
- deleted 2y ago
  [deleted]
- bArray 2y ago
  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/S2452302X24002869 https://www.sciencedirect.com/science/article/pii/S2452302X2... [2] https://www.sciencedirect.com/science/article/pii/S2161831322006810 https://www.sciencedirect.com/science/article/pii/S216183132...
bArray 2y ago
To reply to a now deleted comment about weight loss: You will still lose "muscle", and some of that will be in the fat embedded into the muscle. I would recommend checking out some of the learnings from the keto diet. You may or may not subscribe to it, but they had to very carefully tread these lines when the body was essentially in starvation mode. A few things I know of: 1. You have to maintain a certain amount of protein intake (~10% to ~20%) to prevent your body burning lean muscle mass. 2. Too much protein gets converted into sugars, these in turn are easily stored as fats. 3. Maintain exercise, use it or lose it. 4. Don't over-exercise. "Exercise flu" results in limited performance and muscle loss through gluconeogenesis. You break down muscle and convert it to energy due to lack of carbohydrates.
kozikow 2y ago
I used Ozempic for couple months. I lost 25kg over 6 months (120kg -> 95kg). I gained muscle, as I started weightlifting (modified 5x5 program 3-4 times a week) and was supplementing with protein isolate (about 50g a day). My subjective feeling is that even if "Ozempic makes you lose muscle faster than the same caloric deficit without it" is true, this effect is very small. Vast majority of muscle loss comes from no resistance exercise, low protein, much faster weight loss than possible "naturally".
ohuhu 2y ago
[flagged]
muffwiggler 2y ago
[flagged]
lenerdenator 2y ago
I was wondering when the other shoe would drop. 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. We'll decay people's heart muscles before we put a tax on unhealthy food to help fund Medicare and Medicaid.
- autoexec 2y ago
  > 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.
- omegaworks 2y ago
  > 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-access-in-the-united-states https://www.aecf.org/blog/communities-with-limited-food-acce... 2. https://www.economist.com/finance-and-economics/2023/11/09/in-praise-of-americas-car-addiction https://www.economist.com/finance-and-economics/2023/11/09/i...
  - lenerdenator 2y ago
    Then fund the stores through the Medicaid funds generated. Gotta start somewhere.
    - omegaworks 2y ago
mensetmanusman 2y ago
Ozempic can use their cash to start an exoskeleton division.
msarrel 2y ago
This study is garbage. You can only trust what the companies that profit from the drugs publish.
brodouevencode 2y ago
There are no free lunches in nature.
mslack616 2y ago
I'm a fan of open bodybuilding, so I've been following the Ozempic usage trend for a while now. Given the findings on this study, I can see how it may become an essential drug on bodybuilders stacks. Hunger reduction + supraphysiological muscle gain from steroids and growth hormone - (heart) muscle reduction = win/win? Heart problems are one (of many) of the main problems these guys face, so I won't be surprised if Ozempic is used to kind of "balance" the effects of other drugs.
- adbge 2y ago
  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.
csours 2y ago
These comments make me very sad about scientific literacy. 342 comments and 'control' appears 12 times (before this comment). Without proper control you could also say that weight loss is associated with loss of heart muscle mass.
pogue 2y ago
It would seem wise to potentially add a low dosed anabolic androgenic steroid like Anavar (Oxandrolone) [1] during a course of Ozempic. This would help keep skeletal muscle in tact during a calorie deficient period. A low dose wouldn't be expected to cause much, if any, side effects. But it's something that would be best put through rigorous studies. But bodybuilders have been using tricks like these for decades (obviously at much more ridiculously high amounts) that work quite successfully for this exact purpose. [1] https://en.wikipedia.org/wiki/Oxandrolone https://en.wikipedia.org/wiki/Oxandrolone
- heroiccocoa 2y ago
  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-methylbutyric_acid https://en.wikipedia.org/wiki/%CE%92-Hydroxy_%CE%B2-methylbu...
  - cthalupa 2y ago
    Most data on HMB shows that it is effective in preserving muscle mass in people with cancer cachexia or the eldery, results are generally not great for those without specific diseases or of younger age. I'm still taking it because it's cheap and I figure I might as well, but anavar is likely significantly more effective.
    - pogue 2y ago
      Yes, HMB is another compound that would be potentially very beneficial during catabolic times such as extreme weight loss. The typical dosage would be 3g/day. Examine has done excellent write ups on all the research related to it, which can be found below. They recently paywalled the bulk of it, but it's still on the wayback. https://web.archive.org/web/20240310004421/https://examine.com/supplements/hmb/ https://web.archive.org/web/20240310004421/https://examine.c...
Suppafly 2y ago
which weight loss drug?
z3ncyberpunk 2y ago
Who would have thought cheating to lose weight would have side effects?

372 points by Eumenes 2y ago

It seems the article isn't just saying it's heart muscle that's being lost but regular muscle in general. Even more so than in a low calorie diet.

sfink 2y ago
There's a linked article saying that 40% of the weight loss is muscle.
- com2kid 2y ago
  Outside of cardiac muscle, which is a bit worrisome, 40% of weight loss being from muscles is incredibly typical for any diet that sheds pounds. There are very complex dietary regimes that can be followed to minimize this, but most studies have shown that they don't save any time compared to losing weight and then working to get the muscle back afterwards. > Dyck’s study comes on the heels of a commentary published in the November issue of The Lancet by an international team of researchers from the U of A, McMaster and Louisiana State University who examined emerging research showing that up to 40 per cent of the weight lost by people using weight-loss drugs is actually muscle. This is, again 100% typical of what happens with caloric restriction.
  - throwup238 2y ago
    Literally the next line after the 40% quote: > Carla Prado, a nutrition researcher in the Faculty of Agricultural, Life & Environmental Sciences and lead author on the commentary, 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 — including decreased immunity, increased risk of infections and poor wound healing. Do you have a source that 40% muscle loss is typical for a caloric restriction diet without GLP1 agonists?
    - com2kid 2y ago
      > Do you have a source that 40% muscle loss is typical for a caloric restriction diet without GLP1 agonists? OK I actually checked up on this, and it is more like 30%, but that number gets worse as you get older. For young healthy men it can be 20%, but as you get older that number gets worse and worse. I'd want to see a comparison of a similar cohort of people going on a calorie restricted diet of the same magnitude, with a similar (lack of) activity levels. The study at https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00272-9/abstract https://www.thelancet.com/journals/landia/article/PIIS2213-8... compares people who had less overall weight loss on a pure calorie restricting diet, which, well, by definition isn't the same thing.
  - loeg 2y ago
    > There are very complex dietary regimes that can be followed to minimize this The dietary regime isn't complex -- just consume a LOT of protein. Something like 1-2 g/kg/d. And non-dietary: do strength training.
    - devmor 2y ago
      Yep, I can anecdotally confirm as I’m on such a routine right now. I started losing weight from severe obesity with a caloric deficit but noticed I was also feeling weaker in general (aside from the tiredness that comes with eating under your TDEE). I started going to a trainer and he had me change my macros so that I was consuming about 200g of protein per day in addition to 4 days per week of full body workouts on top of my cardio. Since then I’ve lost an additional 150% of my initial weight loss, and have gained moderate muscle mass on top of that.
    - com2kid 2y ago
      This works until it doesn't. Professional body builders do bulk/cut/bulk/cut because after awhile you can't lose weight and put on muscle at the same time, especially if you want to get to the point of being shredded. (well you can do it, but there is no benefit over bulking and cutting)
      - loeg 2y ago
        This comment is not responsive to mine. I am talking about minimizing muscle loss during weight loss, not losing weight and putting on muscle at the same time. And bodybuilders do exactly what I said during their cut phases -- to minimize muscle loss. (Most people losing weight on these drugs are not bodybuilders.)
derektank 2y ago
From the commentary, >Studies suggest muscle loss with these medications (as indicated by decreases in fat-free mass [FFM]) ranges from 25% to 39% of the total weight lost over 36–72 weeks. This substantial muscle loss can be largely attributed to the magnitude of weight loss, rather than by an independent effect of GLP-1 receptor agonists, although this hypothesis must be tested. By comparison, non-pharmacological caloric restriction studies with smaller magnitudes of weight loss result in 10–30% FFM losses. Comparing weight loss of different magnitudes is kind of comparing apples to oranges. Of course, it's not really possible to get persistent, large magnitude weight loss any other way than by using these drugs, so I understand why the comparison was made.

therein 2y ago

I like how they aren't saying Semaglutide in the title in an attempt to perhaps keep it from immediate scrutiny.

neom 2y ago
https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss https://www.fda.gov/drugs/postmarket-drug-safety-information... Same thing??
- therein 2y ago
  > Unapproved GLP-1 Drugs Used for Weight Loss Yeah that would be perfect. But editorializing it to the point of calling it `weight loss drug`, just feels like it is begging for the reaction of "oh yet another weight loss drug".
- TylerE 2y ago
  No. That’s talking about the compounded versions (NOT in an auto pen) that were temporarily allowed due to shortages, but whose authorization has since been revoked.
rzzzt 2y ago
The first link goes to the study and it does mention the ingredient: https://www.sciencedirect.com/science/article/pii/S2452302X24002869 https://www.sciencedirect.com/science/article/pii/S2452302X2...
- therein 2y ago
  I am talking about UAlberta's title specifically.
  - rzzzt 2y ago
    "Semaglutide Reduces Cardiomyocyte Size and Cardiac Mass in Lean and Obese Mice" was also written by UoA researchers. I don't see anything nefarious in the choice of the title for the news blurb.

jongjong 2y ago

As a coder, I'm realising more and more that the human body isn't so different from a computer. When you try to fix something without having complete understanding of all the relevant parts of the system, you will invariably introduce new issues. With a machine as complex as the human body, it seems inevitable that the field of medicine would be a game of whac-a-mole. Finding solutions which don't create new problems is hard and should not be taken for granted.

kylehotchkiss 2y ago
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
- jongjong 2y ago
  Yes 100%. That's why I never understood the rollout of MRNA vaccines during COVID. It's like pushing a massive code change straight to production during peak traffic and without the normal phased rollout. I totally understand where conspiracy theorists are coming from. That didn't seem right.
  - kylehotchkiss 2y ago
    yeah, it's too bad the tech didn't have a better way to gain peoples trust (through some other breakthrough with the normal set of clinical trials). I think the solve was impressive (tell cells to produce a protein that looks exactly the same as the viruses and place it outside the cell to piss off antibodies) but protein-protein interaction data is hard to come by. Maybe these guys can figure it out https://www.aalphabio.com https://www.aalphabio.com
  - _yb2s 2y ago
    It made sense to me- they made a risk vs benefit decision under high uncertainty, factoring in the massive harm that the ongoing pandemic was already causing. There had already been 12 years of human clinical trials for other mRNA vaccines, and they still did extensive clinical trials for the new covid vaccine before rolling it out. In hindsight they were exactly right- and they saved at least tens of million of lives by acting quickly[1]. [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC9537923/ https://pmc.ncbi.nlm.nih.gov/articles/PMC9537923/

wizzard0 2y ago

well that's a weight reduction too! on a more serious note, could it be that the load on the muscle gets lower so they adjust? 8% reduction for 30% body weight reduction sounds reasonable to me at first glance

cm2187 2y ago

> emerging research showing that up to 40 per cent of the weight lost by people using weight-loss drugs is actually muscle That's the sort of headlines that smells like bullshit to me. My understand of those drugs is that they don't actually make you lose weight, they just cut your appetite so you can follow a diet to lose weight without hunger hammering at the door. So to start with, if that's the case, all they are observing is the effect of a diet. Not sure the diet drug has much to do with it. Then I went from 133kg to 88kg with these diet drugs. Even though I exercised every day, I am sure I also lost some muscle mass as well, just because I don't have to carry 45kg every time I make a move anymore. Seems logical and would probably be concerned if it was any other way.

taeric 2y ago
Yeah, folks don't like thinking that obese people have a lot of muscle needed to move around. And losing weight is losing all weight.
hnthrowaway0328 2y ago
Just curious, does your appetite come back whence you cut off the meds? The only reason I want to lose weight is to eat more freely, won't be useful if I lose my appetite too.
- 0xB31B1B 2y ago
  Appetite comes back yes
- andreareina 2y ago
  It does.
- xeromal 2y ago
  I saw someone mention that they craved heroin less on ozympic.
- cm2187 2y ago
  You don't lose taste, you lose your appetite, which means you can resist the temptation to eat easily, and you feel full very quickly. That doesn't prevent you from eating what you like, but it does help you to not eat too much of it, which I hope is not what you mean by "more freely". The appetite comes back when you cut the meds, but it's an appetite based on your new weight. But if you then go on a some suggar rampage, you will regain weight and your appetite will grow too. Those drugs are merely a guard rail to complete a diet successfully, but if people do not change their eating habbits, the same causes will produce the same effects after they cut the meds.

PlunderBunny 2y ago

I like the way the title ends with "human cells" as if the main reason it was there was to cut off (?) all the people that respond with "In mice."

loeg 2y ago
Well, in vitro.

xyst 2y ago

folks, this is why I lean on skepticism in regards to “off label” usage (ie, weight loss). Have only lived a few decades on this planet and the weight loss trends with pharmaceuticals is wild.

ahahahahah 2y ago
Weight loss is not "off label" for this drug.

delichon 2y ago

It also decreases gut motility, which helps with the intended effect of appetite suppression. Young healthy people tend to shrug at that. As an old person that takes it right off the menu even before I read about accelerated sarcopenea. Maybe it's the same effect on the peristaltic muscles.

vundercind 2y ago
A bare glp-1 agonist doesn’t, I think, but the weight loss versions are double-acting and do also slow digestion.
- loeg 2y ago
  Tirzepatide (Zepbound) is double-acting but semaglutide (Ozempic) isn't. Both are prescribed for weight loss.
Auracle 2y ago
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.

httpz 2y ago

Some of the side effects of semaglutide are just a result of eating less calories. Without a control group who also ate the same amount of calories but without the drug, it's hard to know if the side effect were directly caused by semaglutide or just a result of being in a calorie deficit.

hackernewds 2y ago
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.

renewiltord 2y ago

This is going to be a non-result. It won't matter. The win from losing weight will easily outclass all of this. This drug should be in wide circulation. When the patents expire, we will enter a new era of American health.

loeg 2y ago

So like, it's interesting that this happens in mice, but we did not see increased heart disease in human RCTs of these drugs. Maybe the mouse dose is just absurdly high? "Mice were then administered semaglutide 120 μg/kg/d for 21 days." That could be vaguely reasonable -- human doses range from, idk, ~36 to ~200 μg/kg/d (2.5mg/week to 15mg/week at ~100kg).

7e 2y ago
They found the mice did not suffer from any heart problems, so it’s not surprising.
cthalupa 2y ago
> 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.

DidYaWipe 2y ago

So... could this be a treatment for enlarged hearts?

FollowingTheDao 2y ago
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://pmc.ncbi.nlm.nih.gov/articles/PMC5939638/ https://www.proteinatlas.org/ENSG00000112164-GLP1R/tissue 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.

LeoPanthera 2y ago

It's my understanding that if you have hypertension, your heart muscle grows thicker as a consequence of working harder against your blood pressure, which reduces the flow capacity of your heart. So if you have hypertension, this might actually be a "good" side-effect?

rootsudo 2y ago
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.

deleted 2y ago

[deleted]

akira2501 2y ago

The marketing is astounding. "Weight-loss drug." Oh, would that be Semaglutide? <click> Hey, would you look at that!

bastawhiz 2y ago

The research says > Together these data indicate that the reduction in cardiac size induced by semaglutide occurs independent of weight loss. Which does sound concerning. It's the drug, not the weight loss, that causes the muscle loss. I guess the question is whether it's better than nothing. Is the loss in lean muscle a worse outcome than remaining obese?

jyscao 2y ago

[flagged]

vundercind 2y ago
At the very least, we should expect to see the same kinds of downsides you’d see for anyone who managed to eat way, way less and lose weight at a multiple-pounds-per-week rate for weeks and weeks on end without taking a drug to do it. They’d be truly miraculous if they achieved their results without even the same cost as doing the same thing without the drug.
monero-xmr 2y ago
No one seems to remember Fen Phen or its stratospheric rise and fall https://en.m.wikipedia.org/wiki/Fenfluramine/phentermine https://en.m.wikipedia.org/wiki/Fenfluramine/phentermine
- Someone1234 2y ago
  No one who brings up Fen Phen seems to grasp how long both that and GLP-1s have been on the market. We're up to 4x Fen Phen's run already (5-years Vs. 20-years). GLP-1 Agonists aren't new, they've just been approved for additional usages. So why, after 20-years, and millions of people haven't fen-phen-like side effects appeared?
- MBCook 2y ago
  That was one of my first thoughts. It’s perfectly possible for a new hot to have a severe side effect that won’t be noticed for quite a long time. Semiglutide appears to have undergone final clinical trials in the US around 2017. Given it hasn’t been on the market terribly long and has only an exploded in popularity relatively recently it doesn’t seem like it would be that hard for it to have a serious side effect in a small portion of the population that hadn’t been detected before due to the limited number of people taking it, the amount of time it takes to manifest, or both. Obviously it’s providing significant benefit that risk could easily be worth it. But as it gets marketed towards more and more people that won’t be true for all of them.

oksurewhynot 2y ago

I thought this was known about older GLP-1 antagonists like semaglutide, which is why there's some excitement around the newer dual-action types like tirzepatide? My understanding is the newer drugs cause substantially less muscle mass loss.

CyanLite2 2y ago

If you’re 20% smaller, it would make sense that your heart could pump 20% less.

dgfitz 2y ago
Uh, I think most highly in/shape people have normal sized, very healthy hearts and their bpm is like 45. Their hearts are not physically smaller, nor did they shrink during their build-up to current physique. Saying things like this is harmful at best. Please don’t.

wileydragonfly 2y ago

Don’t care. I’m down 30lbs.

jmward01 2y ago

I wish discussions would focus on all source mortality instead of single stat x. If the all source mortality data comes back favorably you could read the interpretation of this data 100% opposite: regular calorie restricting diets fail to reduce heart size... Point being, without all source mortality data to back up that this is a bad thing it is a very hard stat to care about.

acyou 2y ago

The study found that heart muscle decreased in both lean and obese mice. So any observed muscle loss might not be just from losing body mass and not having to work as hard. But if you're already lean and then go on a calorie deficit (as a result of decreased appetite from taking the drug), then muscle mass will be lost through metabolism of muscle and other tissue. Then the study states further that the proportion of muscle loss is higher than expected from calorie restriction alone. My gut feeling here is that where there's smoke there's fire, and I predict dramatic class action 40 years in the making, either like tobacco, or like baby powder, depending on the actual long term health outcomes. And, this is great research! We need more like this ASAP!

derbOac 2y ago
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.

GenerWork 2y ago

I hope they re-run this study with retatrutide vs semaglutide. Apparently retatrutide does a better job at preserving muscle, and some bodybuilders will take small dosages (.5 - 1mg a week) of it in order to lose stubborn fat but keep muscle.

loeg 2y ago
How are bodybuilders getting a phase 2 trial drug still in development by Lilly?
- cthalupa 2y ago
  China. It's trivial to purchase retatrutide, semaglutide, tirzepatide, and a wide variety of other peptides from Chinese labs, and for pennies on the dollar compared even to compounding pharmacy prices.

ramesh31 2y ago

>My understand of those drugs is that they don't actually make you lose weight, they just cut your appetite so you can follow a diet to lose weight without hunger hammering at the door. While acknowledging that the mechanism is different, this was the same effect of Ephedrine, which went through a similar craze as Ozempic before the full complications were known. My bet is that this will be similar, where the risks end up being outweighed by the benefit for extreme obesity and diabetics, but that the cosmetic weight loss aspect of it will become outlawed or highly regulated.

dyauspitr 2y ago

Sounds like a perfect counter to using steroids in bodybuilding which can cause an enlarged heart. I wonder if we will start seeing GLP-1 in bulk cut cycles more moving forward.

talkingtab 2y ago

It concerns me how discussions, such as this one go on HN. This is an important topic. With the epidemic of obesity we now find a drug that appeals to a large number of people. This is an important topic as well. What is the current comment receiving most of the comment? "That's the sort of headlines that smells like bullshit to me" That's the sort of comment that smells like bullshit to me. What kind of place is this? Many times I find the posts on HN interesting, but increasingly these kind of comments make me wonder about Y Combinator. Is this really the best they can do? And for us readers who are supposed to be so called hackers, is this the best we can do?

throwaway2037 2y ago
I agree 100%. Those kinds of comments have no place, and add little to nothing to the discussion. Many HN discussions outside of pure tech invite all kinds of crazy and uninformed comments -- health/diet, finance/economy, etc.
elevatedastalt 2y ago
The HN you are yearning for disappeared about 8-10 years ago when it was largely taken over by normies and people way outside the hard-core-tech fold. It's not very different from Reddit front-page now if the topic is even remotely political. For purely technical topics you expect good quality discussion, but those threads barely get comments in the two digits.
- deleted 2y ago
  [deleted]
- patrickhogan1 2y ago
  Yes sometimes the loudest voice definitely rises to the top and it’s annoying, but I also think it’s a condition that too many new members don’t know how to use the upvote button. I also think it’s a symptom that HN does not allow enough people to use the down vote button. you could be a commenting member for years and not be able to downvote or you could be somebody who posts a few click bate links you copied from another aggregator and all of a sudden you have the ability to downvote. It’s pretty dumb.

et2o 2y ago

This is most likely a good thing. It isn't killing cardiac myocytes, it's probably assisting with reverse remodeling. Fits with why we know it helps in heart failure.

quantumwoke 2y ago

Seems like some of the comments need to learn that a big hypertrophic heart is much worse for you than a normal sized heart. Folks: GLP-1s have demonstrated benefit from heart failure, and this heart muscle change is probably mechanistic in that.

7e 2y ago

“Dyck, who is the Canada Research Chair in Molecular Medicine and heads up the Cardiovascular Research Centre, says his team did not observe any detrimental functional effects in hearts of mice with smaller hearts and thus would not expect any overt health effects in humans.” This makes sense. If fasting hurt your heart many of your ancestors would have died early. There is strong selection pressure to survive extended fasts.

siliconc0w 2y ago

It's pretty clear that GLP-1 should be prescribed with protein powder. 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). IMO this and a lack of resistance training (which should also be prescribed) probably makes up a large % of the muscle loss on these drugs. The problem is that the FDA only looks at dumb measures like weight lost, not body fat % when approving these drugs.

meragrin_ 2y ago
> 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.
cthalupa 2y ago
I find it significantly easier to eat healthy on tirzepatide, fwiw.
technofiend 2y ago
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.
phil21 2y ago
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.
jf22 2y ago

kbos87 2y ago

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.

mgiampapa 2y ago
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.
NavinF 2y ago
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)
cthalupa 2y ago
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.
- xk_id 2y ago
  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.

mistercheph 2y ago

There is no way magic weight loss pill with no side effects could possibly go wrong!!!

robwwilliams 2y ago

Not a solid paper—-more like an abstract. I could not find any information on the strain or type of mice they studied. Data from one strain often fails to generalize to others. Trying to leap to human implications is beyond risky.

insane_dreamer 2y ago
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.
- robwwilliams 2y ago
  Yes, you are right, but ideally a team should test several genetic backgrounds of mice. Almost all cancer treatments have some negative effects. It is crucial to know what genetic and exposure variables to avoid to maximize therapeutic benefits. Cadmium in some strains of mice is highly toxic to male testes. But if, as in the C57BL/6J strain, you have a “lucky” transporter mutation, then no problems at all. This kind of variability has been known since the turn A. Garrod in the early 1900s. And ignored by many. Here is the data on the cadmium example I just mentioned: https://genenetwork.org/show_trait?trait_id=13035&dataset=BXDPublish https://genenetwork.org/show_trait?trait_id=13035&dataset=BX...
jr000 2y ago
It says in the paper they used 21-week-old male C57BL/6 mice, as well as AC16 human immortalized cardiomyocytes
- robwwilliams 2y ago
  Ah, thanks. I looked but not carefully enough! C57BL/6 – the canonical inbred fully homozygous mouse that unfortunately is used as the “HeLa cell” of almost all experimental murine biomedical research. I understand the reason this happened, but there is no excuse in 2024 to use just one genome (and an inbred one at that) to test translational relevance. Consider this work a pilot worth testing in NZO, DBA, A, C3H and BALB strains and some F1 hybrids. Whatever the results they should have good generality to mice in general.

tomhoward 2y ago

I'm not commenting specifically on the heart-muscle aspect of the study, but it shouldn't be a surprise that the weight loss from this drug is significantly attributable to muscle loss; it almost always is when dieting. It's the same with keto/low-carb or any other kind of caloric-restrictive dieting (which Ozempic facilitates). The modern weight-loss programs I'm seeing now (at least those aimed mostly at middle-aged men) emphasize consuming significant amounts of protein (2g for every 1kg of body weight each day) and engaging in regular resistance training, in order to maintain muscle mass. The article addresses this: To keep muscle strong while losing weight, Prado says it is essential to focus on two main things: nutrition and exercise. Proper nutrition means getting enough high-quality protein, essential vitamins and minerals, and other “muscle-building” nutrients. Sometimes, this can include protein supplements to make sure the body has what it needs. Perhaps there needs to be more formal research into this, and a strong recommendation made to everyone using these drugs that this kind of diet and exercise plan is vital.

jjallen 2y ago
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.
- phil21 2y ago
  Not sure how much I lost during, but a substantial amount. I have been working out since about 20lbs from my goal weight and now roughly a year later - and have gained strength (based on the numbers I can lift) from before I lost 100lbs. I don’t think it would have been possible to not lose substantial muscle mass while rapidly losing 100lbs over 9mo, even with extreme resistance training added to the mix. While DEXA scans are not super accurate, I’ve put on about 17lbs of muscle since my first scan 10mo ago, while maintaining a 12% or less bodyfat ratio. That said, I’ve been eating extremely healthy both before and after being on the drug which helps a lot. The drug simply gave me the mental space to avoid the binges which were my particular problem. That and it controls portion sizes to European dinner vs. American restaurant sized meals for me.

diath 2y ago

The problem with appetite suppression drugs is that they simply make you not feel hungry, but do nothing to fix your lack of discipline and self-control, I'm sure most people who lose weight on these drugs, and then come off, will just go back to their bad habits.

echoangle 2y ago
So why not just stay on the drugs?
- diath 2y ago
  You technically could but the idea here is to cut the excess bodyfat percent and get into the healthy range, rather than to keep losing weight, which itself is also unhealthy, but once you become dependent on the drugs to maintain your weight, without fixing your habits, you will just go between getting off the drug, binge eating, gaining the weight back, and hoping back on the drug and losing weight while barely eating, I can't imagine bouncing between such two extremities being good for your health.
  - echoangle 2y ago
    Can’t you just adjust the dosage to stabilize?
    - phil21 2y ago
      Yes, you can. Or most people can. It’s called a maintenance dose and is usually the minimum dose available for the particular drug you are on. As these become more common and doctors more aware, the dosing guidelines will become much more nuanced and dialed in.
  - cthalupa 2y ago
    Well, lots of people back off those dosages once they reach their goal weight and have minimal difficulty maintaining. As we know more about the long term effects of staying on the drug, it's totally possible it might make sense just to keep on it. But as someone who spent a good chunk of their early adulthood having no problem with healthy habits and then slowly slipping into tons of bad ones, getting on tirzepatide has made it as easy for me to make those healthy choices that I made when I was in my 20s. Ones that I struggled with mightily after I got fat. Hopefully more and more people will use them as a tool to help them get things back and order and then stay there, whether or not they keep taking it.

dukeofdoom 2y ago

If it causes cellular damage, it might be a big problem. "Some studies indicate that only about 1% of heart cells are renewed each year in younger people, dropping to about 0.5% by age 75. This means that a significant portion of heart cells remain from childhood into old age."

raverbashing 2y ago

Keyword: "in mice" Second gotcha: how much of the decrease is just attributed to the lower mass of the subject after the weigh-loss treatment Though it's one good reminder that "catabolism" and "anabolism" are less selective than we wished to

Anotheroneagain 2y ago

I've been warning people for a long time that the drug only fakes the signal of fullness from the gut, and only makes you starve yourself. It doesn't actually fix anything.

deleted 2y ago
[deleted]

heisenbit 2y ago

It may be worth considering that a heavier person needs a stronger heart than a lighter one. The heavier weight also acts as a constant load/training. Without some degree normalization we won‘t know whether this is normal or concerning.

Etheryte 2y ago
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.
- ben7799 2y ago
  I think doctors can figure out real quick which version of heart enlargement you have. The athletes heart is going to beat at 1/2-1/3 the rate at rest compared to the obesity-enlarged heart and a stress test is going to show the athletes upper heart rate limits are much much higher.
  - Etheryte 2y ago
    This is pretty much exactly what I said?

lofaszvanitt 2y ago

Erm, when you lose weight you usually lose muscle too. So compared to people on a diet and people on ozempic, what's the plus percentage of muscle loss?

crazygringo 2y ago

I'm always so baffled by warnings about losing muscle when losing weight. Of course you do! If your body is tens of pounds lighter, then you don't need the extra muscle to lug it around. This paper is about reduction in heart muscle, and of course your heart doesn't need to be as strong because there's less blood to pump and less tissue to fuel. 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. Our bodies are really good at providing exactly the amount of muscle we need for our daily activities (provided we eat properly, i.e. sufficient protein), so it's entirely natural that our muscles decrease as we lose weight, the same way they increased when we gain weight. Muscles are expensive to keep around when we don't need them. Obviously, if you exercise, then you'll keep the muscles you need for exercising. But this notion that weight loss can somehow be a negative because you'll lose muscle too, I don't know where it came from. Yes you can lose muscle, but you never would have had that muscle in the first place if you hadn't been overweight -- so it's not something to worry about.

antihero 2y ago
What they need is to design some sort of mouse gym.
- zenomadic 2y ago
  MouseLifts 5x5 + RAtkins diet
  - gonzo 2y ago
    "Gym rats" was already a thing.
deleted 2y ago
[deleted]
bArray 2y ago
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/S2452302X24002869 https://www.sciencedirect.com/science/article/pii/S2452302X2... [2] https://www.sciencedirect.com/science/article/pii/S2161831322006810 https://www.sciencedirect.com/science/article/pii/S216183132...

bArray 2y ago

To reply to a now deleted comment about weight loss: You will still lose "muscle", and some of that will be in the fat embedded into the muscle. I would recommend checking out some of the learnings from the keto diet. You may or may not subscribe to it, but they had to very carefully tread these lines when the body was essentially in starvation mode. A few things I know of: 1. You have to maintain a certain amount of protein intake (~10% to ~20%) to prevent your body burning lean muscle mass. 2. Too much protein gets converted into sugars, these in turn are easily stored as fats. 3. Maintain exercise, use it or lose it. 4. Don't over-exercise. "Exercise flu" results in limited performance and muscle loss through gluconeogenesis. You break down muscle and convert it to energy due to lack of carbohydrates.

kozikow 2y ago

I used Ozempic for couple months. I lost 25kg over 6 months (120kg -> 95kg). I gained muscle, as I started weightlifting (modified 5x5 program 3-4 times a week) and was supplementing with protein isolate (about 50g a day). My subjective feeling is that even if "Ozempic makes you lose muscle faster than the same caloric deficit without it" is true, this effect is very small. Vast majority of muscle loss comes from no resistance exercise, low protein, much faster weight loss than possible "naturally".

ohuhu 2y ago

[flagged]

muffwiggler 2y ago

[flagged]

lenerdenator 2y ago

I was wondering when the other shoe would drop. 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. We'll decay people's heart muscles before we put a tax on unhealthy food to help fund Medicare and Medicaid.

autoexec 2y ago
> 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.
omegaworks 2y ago
> 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-access-in-the-united-states https://www.aecf.org/blog/communities-with-limited-food-acce... 2. https://www.economist.com/finance-and-economics/2023/11/09/in-praise-of-americas-car-addiction https://www.economist.com/finance-and-economics/2023/11/09/i...
- lenerdenator 2y ago
  Then fund the stores through the Medicaid funds generated. Gotta start somewhere.
  - omegaworks 2y ago

mensetmanusman 2y ago

Ozempic can use their cash to start an exoskeleton division.

msarrel 2y ago

This study is garbage. You can only trust what the companies that profit from the drugs publish.

brodouevencode 2y ago

There are no free lunches in nature.

mslack616 2y ago

I'm a fan of open bodybuilding, so I've been following the Ozempic usage trend for a while now. Given the findings on this study, I can see how it may become an essential drug on bodybuilders stacks. Hunger reduction + supraphysiological muscle gain from steroids and growth hormone - (heart) muscle reduction = win/win? Heart problems are one (of many) of the main problems these guys face, so I won't be surprised if Ozempic is used to kind of "balance" the effects of other drugs.

adbge 2y ago
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.

csours 2y ago

These comments make me very sad about scientific literacy. 342 comments and 'control' appears 12 times (before this comment). Without proper control you could also say that weight loss is associated with loss of heart muscle mass.

pogue 2y ago

It would seem wise to potentially add a low dosed anabolic androgenic steroid like Anavar (Oxandrolone) [1] during a course of Ozempic. This would help keep skeletal muscle in tact during a calorie deficient period. A low dose wouldn't be expected to cause much, if any, side effects. But it's something that would be best put through rigorous studies. But bodybuilders have been using tricks like these for decades (obviously at much more ridiculously high amounts) that work quite successfully for this exact purpose. [1] https://en.wikipedia.org/wiki/Oxandrolone https://en.wikipedia.org/wiki/Oxandrolone

heroiccocoa 2y ago
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-methylbutyric_acid https://en.wikipedia.org/wiki/%CE%92-Hydroxy_%CE%B2-methylbu...
- cthalupa 2y ago
  Most data on HMB shows that it is effective in preserving muscle mass in people with cancer cachexia or the eldery, results are generally not great for those without specific diseases or of younger age. I'm still taking it because it's cheap and I figure I might as well, but anavar is likely significantly more effective.
  - pogue 2y ago
    Yes, HMB is another compound that would be potentially very beneficial during catabolic times such as extreme weight loss. The typical dosage would be 3g/day. Examine has done excellent write ups on all the research related to it, which can be found below. They recently paywalled the bulk of it, but it's still on the wayback. https://web.archive.org/web/20240310004421/https://examine.com/supplements/hmb/ https://web.archive.org/web/20240310004421/https://examine.c...

Suppafly 2y ago

which weight loss drug?

z3ncyberpunk 2y ago

Who would have thought cheating to lose weight would have side effects?