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.
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.
Even amongst traditional calorie deficits, rapid weight loss results in greater loss of muscle mass when compared to gradual weight loss, even if you lose the same amount of mass overall. I.e. you keep more muscle losing 0.5 lbs a week over 40 weeks than 2 lbs a week over 10 weeks.
Can you provide a single high quality (randomized) study demonstrating GLP1 therapeutics are 'incredibly detrimental to [your] longevity and quality of life'?
Consider the type of confounding that occurs in studies of people losing a lot of lean mass: cachexia, restriction to bed, famine.
Traditional weight loss methods have not shown the magnitude of survival benefits wrt cardiovascular disease, joint pain, diabetic complications. Exercise is wonderful, but as a public health intervention it is not sufficient.
If anyone looks at the totality of the high quality GLP1 clinical evidence and concludes these drugs are going to cause a net reduction in longevity and quality of life, then they should step back and assess their process for evaluating information.
If I'm reading the study [1] correctly, that conclusion is not warranted.
It appears that they fed the control group and treatment group of mice lots of food to get them fat, then gave them identical normal diets, and gave the treatment group semaglutide.
The semaglutide group lost significantly more weight (fig A.ii) than the control group, and also lost heart muscle.
So it does not seem that they compared to an equivalent amount of weight loss in mice, which is what I'd think you'd need to do to come to the conclusion from the article (actually, not just an equivalent amount of weight loss, but also at the same rate).
> 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
Some years ago there was a crazy science exhibit going around museums in the US that had human cadavers preserved with some plasticizing process where you could see different tissues. They also had cross sections.
They actually had an exhibit showing the effects of obesity on tissues. This was before fat acceptance became a thing. That was really an eye opening exhibit showing shrunken muscle tissue, shrunken hearts, shrunken/squeezed lungs, etc.. in obese people.
Kind of opened my eyes as to how crazy the changes are.
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.
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.
Meta comment here, but Science Direct is an aggregator, and it doesn't make sense to talk about it as publishing. Elsevier published the referenced work in the journal "Advances in Nutrition", vol 8, issue 3, pp. 511-519.
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.
The other thing is conflation between health and fitness. If you are below overweight range, no matter where you are, loosing additional fat is unlikely to make you healthier.
At some level of fat, which is actually more then "thin", you are perfectly fine. Further weight loss is about aesthetic or athletic performance, but has zero effect on health or even slight negative estimated health effect.
Everybody already understands that "losing weight" means losing fat, not muscle. They don't leave the doctors office after a weight warning thinking they need to stop going to the gym.
Likewise, nobody is scared of gaining muscle because they think it will be bad for their health.
> 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?
Well, based on my DEXA scan from before I started on tirzepatide, if I had dropped to 20% BF with my starting LBM, I would have been in close to the best shape of my life. I certainly have a lot of extra muscle in my legs from carrying my fat ass around.
> Does more muscle mass indicate stronger muscles?
Yes. Strength for specific movements involves CNS adaptation, but if you look at the top tier of powerlifters, ranking them within a weight category by MRI muscle mass would produce basically identical results to their actual rankings.
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.
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.
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.
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
This comes from professional bodybuilding, where people are using steroids, along with various, uh, interesting chemicals on the cut[1]. It has almost no benefit to (real) natural bodybuilders. It's closely tied to cycles of steroids.
[1] Ephedrine, Albuterol, Clenbuterol (literally only approved for horses in the US), DNP, and probably more that I haven't heard of. Here's an NIH article on the dangers of DNP, to put it in perspective: https://pmc.ncbi.nlm.nih.gov/articles/PMC3550200/
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.
I’ve seen multiple friends go from eating like shit, including chugging sodas, to not compulsively ordering dessert and no sodas in the house. I think all of them have since quit Ozempic, each seeing some rebound but nothing comprehensive and, most notably to your argument, not in the behaviour modifications.
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.
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.
> For the people who lift weights while on this/these drugs, how much lean muscle do they lose?
I was 92kg when I started on liraglutide (I was doing GLP-1 agonists before it was cool!) and 67% of muscle mass (61kg). I'm now at 69kg and 82% of muscle mass (56kg). I'm doing weight and resistance training twice a week, in addition to aerobic training.
One nice thing, while muscles don't become more massive, they for sure become more pronounced and visible with weight loss.
I know 2 competitive athletes (both MMA) who experimented with it. Both came off of it within ~6 weeks because of complications, mostly related to mood (they got very, very temperamental on it). The athletes in my sphere know about it but aren't interested. The 2 who experimented have a non-trivial social media presence and, ultimately, that is what drove them to experiment.
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.
> 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.
I think it's a mistake to think of it as what people want. It's what people can do.
We have to acknowledge a fundamental struggle that we have with dieting and working out. Pretending it's just hard, when statistics show what is true at a societal level, will not bring us solutions.
We need something else. Either that's massive societal change to i.e. approach something like the diet/workout culture you have in Japan. That's hard. Or, as with many other of our health problems that we can't just will away, it's drugs.
Not believing in progress here, when drugs progress everywhere, is unnecessary. Current generations might have issues. Drugs will be better. We won't.
I don't know it is always avoidance when it comes to diet and exercise. I think oftentimes it comes down to overscheduling. I like to exercise, I like to eat healthy. Those two are oftentimes the first things on my chopping block when I am hurried
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.
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.
The post you are replying to didn't say "always" it said "almost always," wich is perfectly cromulent. And it's also consistent with all the literature I have seen too.
Anecdotally, it takes far less strength training than one would expect, too, to maintain muscle mass. From what I've experienced, 30 minutes a week, given sufficient stimulus, is enough.
Yep. I started resistance training 5x a week about a month in on tirzepatide and even with a severely restricted caloric intake (I just can't eat enough), I've gained LBM.
How did you measure the increase in LBM? This requires very advanced technical equipment. My suspicion is that you have noticed an increase in muscle volume and assumed it to be an increase in muscle mass. Those are largely due to water retention and increased blood flow. They revert quite quickly after you stop exercising for about a week.
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.
If someone is taking this medication for the right reasons, the risks of taking it are far lower than those associated with obesity and diabetes.
Also, concern of losing muscle mass on GLP-1 agonists (and diets in general) is well known and typically explained by the responsible MD to the patient.
> Our meta-analysis showed that GLP-1RA treatment could be associated with a moderate increase in relative risk for thyroid cancer in clinical trials, with a small increase in absolute risk. Studies of longer duration are required to assess the clinical implications of this finding.
It's potentially a possibility, but the absolute risk seems to still be quite low.
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).
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)
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.
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.
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.
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.
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.
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.
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.
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.
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:
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!
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 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.
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.
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?
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.
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.
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.
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.
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.
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.
>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.
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.
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.
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.
“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.
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.
> 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.
> 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.
> 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"
I used to be you - in most of my 20s, I found it very easy to just eat well, east less, etc. It didn't take any willpower on my part to be fit. It was trivial. I didn't understand why fat people didn't just do the same things I was doing. I thought they had to want to be fat!
Then I got busy with other things, I had less and less free time, fast food, etc. got more and more convenient. Then the pandemic happened and I started just ordering uber eats twice a day. And suddenly I realized "holy shit, I'm fucking fat."
And then I tried to go back to my earlier habits, and it was hard. Things that took zero willpower on my part suddenly meant spending a significant portion of my day fighting different urges.
Was it within my power to do so? Sure, in theory. Everyone, given no other task to do but focus their willpower on just not eating too much, could likely eat healthier and lose weight. But that's not reality, it's difficult, and it ends up slipping down the priority list behind a dozen or two other things.
But on tirzepatide, my relationship with food nearly immediately reverted back to how it was when I was younger.
The fact of the matter is, America has a huge amount of obese people that know they shouldn't be and know in theory that fixing their diet and exercising would resolve their issues. And yet they still are fat. Very very very few of them want to be that way. And the reason is it is hard to just eat healthier when you have that level of food craving
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."
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.
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.
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.
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.
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.
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.
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.
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".
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.
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
Perhaps--though worth keeping in mind that the overwhelming alternative is just lifelong obesity, along with all the negative impacts from that.
At least at a societal level, some increased rates of pancreatitis and a little suboptimal muscle loss are peanuts compared to what high obesity rates do to people at scale.
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.
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.
There's tons and tons of error checking- we have at least 5 different error correction and repair systems in DNA, cell cycle checkpoints, and extreme redundancy and feedback homeostasis at nearly every level. Every individual cell has it's own 4 copies of almost every critical gene- two of each chromosome made up of two strands of DNA each. Human bodies can function 70+ years, sometimes with no medical care- something no computer or man made complex machine comes close to.
Beyond specific diseases we understand, it's still mostly a total mystery why we aren't immortal- we have not yet identified what is the basic mechanism of aging, or why it happens at different rates in different species, and mostly our systems are fundamentally capable of repairing and regenerating almost anything, but for some reason get worse and worse at doing so over time. Moreover, this doesn't seem to happen in all organisms- there are many animals that live ~4x human lifespans, and at least one species of jellyfish that is biologically immortal.
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.
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).
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.
> 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.
The next line of the article after that 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.
The rather obvious problem is that these GLP1 agonists don't improve your diet. If you continue to eat a protein and nutrient deficient diet (which is probably a majority of Americans) with caloric restriction on top of that, that leads to excessive muscle loss that you wouldn't see in a weight loss diet. This normally doesn't happen without GLP1 agonists, because these diets are too difficult to stick to for most people. Those who stick to them usually turn to nutritious high satiety whole foods that help combat the negative effects of caloric restriction.
Losing weight without losing muscle mass is very hard. It requires extreme diets like a protein sparring modified fast where 80%+ of your calories are from lean protein while running a 50% caloric deficit. If this research is correct, then using GLP1 agonists shortcuts the feedback loops that make the diets hard to stick to, but they shift the tradeoffs from weight to overall nutrition.
"When a measure becomes a target, it ceases to be a good measure" and all that.
> The rather obvious problem is that these GLP1 agonists don't improve your diet
My understanding from initial anecdotes is this is actually literally wrong. Which was surprising to me, too. But people on GLPs tend to prefer more nutritious food (high protein and high fiber). I'm not sure if this has been studied directly in clinical trials yet but I know that food manufacturers have been reorienting their products toward healthier meal configurations in response to the GLPs.
I predicted the exact opposite of this, but so far I appear to have been wrong.
>Losing weight without losing muscle mass is very hard.
I was with you up to here. In my experience it's easy to maintain a huge proportion of your lean tissue during a weight loss diet: Do some resistance training, get some protein, and don't lose weight too quickly.
There's no need to go to the extreme of a PSMF - which will still have you lose a bunch of muscle on account of being too big a deficit. If you can keep your calories reasonable while on a GLP1 agonist, there doesn't seem to be any reason you'll lose an exaggerated amount of muscle.
> If you continue to eat a protein and nutrient deficient diet (which is probably a majority of Americans)
Is it true the majority of Americans eat a protein deficient diet? I always thought there was too much protein in the western diet - nearly at every meals versus how we would have evolved with somewhat limited access.
I'm pretty skeptical of the "this rate of muscle decline is significantly higher than what is typically observed with calorie-reduced diets" claim. I suspect we're comparing apples to oranges rather than doing like-for-like comparisons at equivalent calories.
I'd like to see the diets in the study that are specified as the "calorie-reduced diets". (Can't seem to find the paper). If it's the same as the Standard American Diet, this muscle loss is quite explainable. I think the mitigation is relatively easy though, if you want to shift the p-ratio, recommending a daily high protein shake would do a lot to stave off muscle loss (and even more if resistance training is applied of course). The exercise addition is probably the hardest to adhere to.
> Losing weight without losing muscle mass is very hard.
Lots of amateur body builders can do it. There are whole training guides about how to lose body fat, but maintain as much muscle mass as possible. Granted, they are probably a minority because they have higher discipline and motivation than the average population.
Losing glycogen stored in muscle is not a huge issue IMO, as it should come back fast. Stuff that's easy to gain is usually easy to lose and vice versa.
> Losing weight without losing muscle mass is very hard.
Yes it is.
> It requires extreme diets like a protein sparring modified fast where 80%+ of your calories are from lean protein while running a 50% caloric deficit.
I’m not any sort of expert but that sounds frankly, dangerous. I don’t see how you do something like that without damaging your liver.
It’s very possible to lose weight and gain muscle, but you have to be at just the right body composition (not lean and not obese) and then there’s a question of “over what period of time”?
Any duration under a month is probably pointless to measure unless you have some special equipment. Any duration over a month and it’s kind of obvious that it is possible. Eat a balanced diet without junk, work out regularly, and keep the calories to only what is necessary.
> The Second Nutrition Report found less than 10% of the U.S. population had nutrition deficiencies for selected indicators.
Another thing that people frequently overlook, since post WW2, the US has been "fortifying" grains with essential minerals and vitamins. That means when people eat cereal and bread from the supermarket (usually highly processed), there are plenty of minerals and vitamins. Say what you like about the highly processed part, few are nutrient deficient.
Yeah, my four donuts per day fill me up just fine or an extra large milkshake and a burger and I’m done for the day with food is definitely happening for some people. Let’s wait and see these drugs might prove to be very beneficial and more testing definitely needed.
where it had been noticed that in humans "the 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", in comparison with muscle loss of only 10% to 30% when the weight is lost just by eating less, without semaglutide.
So with semaglutide, a larger fraction of the weight loss affects muscles than when the same weight is lost by traditional means.
While for other muscles the loss of mass may not be so important, the fact that at least in mice the loss also affects the heart is worrisome and it certainly warrants further studies.
> 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
Emphasis my own. In short: no evidence this is anything other than due to rapid weight-loss.
The latest research I’ve pulled suggests that DEXA scans are fairly inaccurate and aren’t a reliable way to measure body composition even for the same person across time.
MRI is the gold standard, everything else is pretty loosely goosey.
Sorry, no references but this comes up pretty often in the science based lifting communities on Reddit and YouTube if you want to learn more.
I don't have it at hand [edit: [0]] but there are a number of studies showing exercice had more health impact than weight loss (you can combine both of course, but just losing weight has less benefits)
As you point out, losing muscle is common in a diet, and the researchers are well aware of it. Their point was that this aspect is not pushed enough and is drowned by the losing weight part.
From the paper:
> Dismissing the importance of muscle loss can create a disconnect between patients' increased awareness of muscle and the role it plays in health, and clinicians who downplay these concerns, affecting adherence to and the development of optimised treatment plans.
The article does dissect the difference between weight loss drugs and dieting in general. Where they found that muscle mass loss was higher in those that took the drug as opposed to those who followed a calorie restricted diet.
To your point, the drug is absolutely to do with it if by taking the drug people need to be more mindful of the types of food they eat, if they have a smaller window to consume nutrients.
It is most certainly a contributor and for some who may not exercise like you, or consume an appropriate level of protein this research may show that those taking the drug need to focus on a more protein right diet.
Biology is super complicated with lots of surprising dependencies between different biological pathways. So it is possible. That said, I am skeptical as well. For example, if the body sheds 15% of its weight, does the heart naturally shrink by 15% as well? With so many people taking these drugs, there is enough data to begin to profile the rare risks of these drugs in humans (the clinical trials would have found any of the obvious risks)
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.
Experiences vary but I worried I’d, like, not enjoy food on it.
Nope, not a problem. I just get full much faster and am even more prone to simply not eating when I’m busy, than I already was. Not as food-focused when idle, but I still snack a little or whatever.
One of my friends has tried many fad diets, etc. and he finally just went and paid cash for a GLP-1 and he's lost a lot of weight and is feeling much better. If I were in that situation, I would just do the same.
some fun study sort of concluded that the ratio carbs vs fat and protine is the entire mechanic. fat people who eat almost nothing eat only carbs thin people who can eat huge amounts every day eat a lot of fat and protein. Both eat other things just not as much.
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?
>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.
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.
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.
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?
It is my own perception that HN has gotten worse in the six months but these sort of "meta" discussions can be as much part of the problem as part of the solution or possibly a bad smell.
My take it this.
The median scientific paper is wrong. I wrote a wrong paper. The average biomedical paper doesn't fit the standards of the Cochrane Library mostly because N=5 when you need more like N=500 to have a significant result. Since inflationary cosmology fundamental physics has been obsessed with ideas that might not even be wrong.
It's well known that if you lose a lot of weight through diet (and even exercise) you are likely to lose muscle mass. With heavy resistance exercise you might at best reduce your muscle loss if you don't use anabolic steroids and similar drugs. That you could have changes in heart muscle with using these weight loss drugs isn't surprising for me at all and it's the sort of thing that people should be doing research both in the lab and based on the patient experience.
(Funny you can get in trouble if you do too much exercise, spend 20 years training for Marathons and you might get A-Fib because you grew too much heart muscle instead of too little.)
A lot of the cultural problem now is that people are expecting science to play a role similar to religion. When it came to the pandemic I'd say scientists were doing they best they could to understand the situation but they frequently came to conclusions that later got revised because... That's how science works. People would like some emotionally satisfying answer (to them) that makes their enemies shut up. But science doesn't work that way.
The one thing I am sure of is that you'll read something else in 10 years. That is how science works.
The developers of these new peptide-based hormone-acting drugs like semaglutide(ozempic) could be called biohackers, but the system they're hacking on - the human endocrine system - is a delicate system. Introducing semi-synthetic mimics of native hormones can go wrong in all kinds of ways, and hormone-analogue drugs have a poor track record (anabolic steroids, DES, etc.) so extra caution makes sense.
Semaglutide is based on a 31-amino acid polypeptide that mimics the human GLP-1 hormone. At position 26, the lysine side chain is conjugated with a fatty diacid chain, to slow degradation and prolongs half-life, and there are some other modifications. However, the target - the GLP receptor - is not just expressed in the intestinal tract but all through the body, in muscle, central nervous system, immune system, kidneys and others. So some unexpected effects beyond the desired ones are likely.
Semaglutide was recently shown to have potent effects on the heart, and possibly beneficial to certain heart disease conditions associated with obesity. Makes me suspect this drug should be restricted to clinically obese cases where strong intervention with close medical supervision is needed. However for healthy people who just want to lose a relatively small amount of weight it really doesn't seem wise.
"Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization..." (June 2024)
I agree with your desire for what HN should be, and disagree with your assessment that the top voted comment doesn’t support it.
HN is the only forum I know of that has broadly grasped that most so-called “science” outside of the hard sciences and mathematics is complete garbage and driven by funding needs. The world is awash in non-knowledge. This is an extremely serious issue.
Building the skill to rapidly come to a preliminarily judgement of a headline is crucial.
The most reliable source of knowledge we have are in the science. This is further reinforced by technological development that validated the sciences, although at time the technology may precede the science.
> disagree with your assessment that the top voted comment doesn’t support it.
Did you read the paper or skim its abstract, figures, and conclusion? I'm not so sure that commenter did, or they may have cited this,
> Because we report smaller cardiomyocytes in cultured cells and in mice treated with semaglutide, it is tempting to speculate that semaglutide may induce cardiac atrophy. However, we do not observe any changes in recognized markers of atrophy such as Murf1 and Atrogin-1. Thus, we cannot be certain that semaglutide induces atrophy per se or if it does, it may occur via molecular pathways that have not been identified herein.
> Building the skill to rapidly come to a preliminarily judgement of a headline is crucial.
You can't judge this paper based on the popsci headline.
> most so-called “science” outside of the hard sciences and mathematics is complete garbage and driven by funding needs
Based on my reading of the figures and conclusion, I don't think you should call this paper garbage.
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.
After I saw yesterday’s thread about politics in science was flooded with new sockpuppet accounts named after slurs spreading filth and downing everything they don’t agree with I no longer expect anything meaningful from comments here.
HN only works when you have a working assumption that people commenting here are smarter than you. It encourages respect and good faith engagement of content, instead of ad hom, concern trolling, and cargo culting.
It's been years since I've had that mindset when entering any thread above a certain number of comments.
I have noticed this too. The site guidelines say 'no low effort comments', but low effort comments that fit the general zeitgeist are often allowed, while well-thought-out ones that disagree are downvoted. If anyone has a suggestion for an alternative forum focused on technology and science, I really would love suggestions.
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.
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.
For that reason HN should just remove the down/up votes, because it will turn this place to an echo chamber like reddit, these brownie points are useless.
You lose muscle when you lose weight, especially if weight loss is rapid. This is why it's important to be physically active when you're losing weight. It doesn't matter if you're on drug or not.
The source article links to a reference for the 40 percent claim, which itself links to a couple articles that aren't available without a JAMA account.
I can't read the original sources there, but what makes you say its obviously bullshit?
Remember in the 80's and 90's when exercising and being healthy was considered a cool thing? Remember there was a gym on every corner and people were all about looking good and being healthy, eating healthy and living longer?
Then somewhere. . .
- We started normalizing obesity.
- We started this whole "body positivity" trend that celebrating morbidly obese people like Lizzo as positive role models was a good thing?
- We started introducing fat mannequin models in retail stores because being obese shouldn't have a stigma?
Obesity is a problem because we, as a culture have completely normalized obesity. Instead of promoting healthy diets and exercises and saying being obese has consequences like shortening your life and will make you susceptible to various diseases like diabetes and heart disease? All we've done is told people its ok to be obese and eat sugary drinks and over processed foods, because you can just have surgery and that will fix it. Or you can take a pill and that will fix it.
IT WON'T.
IT NEVER WILL.
We've gone down a road that is staggeringly dangerous because we've accepted being morbidly obese as something that's completely normal.
No, some chemical or chemicals got added to the environment around 1980.
All I can say is try losing 20 pounds and keeping it off for two years and how easy it is. Fat shaming might make a difference but I suspect it would be like knocking off 5 lbs from the average where you really need to knock off 50 lbs.
You only started seeing Victoria's Secret getting fat models in the last few years, the obesity epidemic on the other hand started in the Regan years. Maybe it's like taking your belt off when you get heartburn (though I know if I go that route pretty soon I'm going to need suspenders) Try
This is nonsense. The majority of the population don't want to be fat, ugly, and unhealthy and want to persists in maintaining good healthy habits in which they don't eat junk food.
People who promotes fat positivity are ridiculed.
Blaming it on culture overly simplify the issue, which is going to be a complex mix of interacting causes.
You do have to factor in the (probable) cost of not using Ozempic, aka keeping the pounds on. It may be imprecise, but as an example, if a person was likely to die within 10 years at their current weight, any bad effects beyond the 10 year mark have to be heavily discounted.
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.
On the other hand, being overweight takes years off your life:
"Specifically, we found that BMIs from 40 to 44 were associated with 6.5 years of life lost, but this increased to 8.9 for BMIs from 45 to 49, 9.8 for BMIs from 50 to 54, and 13.7 for BMIs from 55 to 59."
I think for some people the roi is measurable and reasonable.
I think this is superstition. Vaccines are a medical intervention that have almost zero downside. There isn’t some mythical cosmic cost-benefit scale that needs to be balanced in every new technology that is deployed.
Vaccines and antibiotics and germ theory are all things that seem “too good to be true” but nevertheless are. Should we be worried that clean fusion power, once commercialized and practical, is going to somehow cause some catastrophic unknown future event just because it yields immeasurable benefit to us?
I think this is just another form of magical thinking.
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?
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.
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.
If you find it hard to control your eating when you always feel hungry, taking a drug to reduce your feelings of hunger is self-control. It's exactly looking at your body as a system and controlling it.
Maybe you can titrate off the drug and in a perfect world, the hunger signal doesn't come back on all the time; that'd be great. Maybe, while on the drug, you've developed eating habits that you can continue while off the drug, even though you feel hungry all the time, again. Maybe, it's just too hard to ignore the hunger signal, and you need the drug for a lifetime.
That's not to say these drugs are necessarily wonderful. Previous generations of weight loss drugs came with nasty side effects that weren't immediately apparent. Fen-Phen was a wonder drug until it ruined people's heart valves. Stimulant appetite supressants have issues because they're stimulants. Cigarrettes have appetite supressant properties (not surprising, nicotine is a stimulant), but they're cigarettes.
Personally, I don't have an overactive hunger signal; so when I eat poorly and gain weight, it's on me. But other people I know have a totally different experience with hunger. If your body is telling you all the time that you need to eat, it's hard to say no. Just like it's hard not to scratch when your skin is itchy. I can resist itchyness sometimes, but when it's constant, I'm going to scratch.
Yeah, I am sceptical, but we'll have to see how it pans out.
Vanishingly few people succeed in exercising discipline and self-control long term. But obesity is caused by food addiction and the idea is once you've kicked the addiction and got over the withdrawal etc then it's gone and you no longer have to fight it. I don't "exercise discipline" to stay thin. I just don't eat copious amounts of junk food because I'm not addicted to it.
So if the drugs are used to soften the withdrawal symptoms such that people can learn to like real food and kick the addictive crap then that's good. But if they're used as a magic pill with no other lifestyle changes then I'm sure people will just go back to what they were doing before once those pangs come back.
I'd still rather we went after the industry peddling the addictive shit. We went after the cigarette companies. But food companies seem untouchable.
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.
Most kill you. If I didn't misread articles on ozempic, they can cause digestive problems where food rots in your stomach. Bad depression was another side effect which blows my mind since you'd think looking better would make you feel great. And these were the minor things.
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.
> 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".
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.
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.
Even amongst traditional calorie deficits, rapid weight loss results in greater loss of muscle mass when compared to gradual weight loss, even if you lose the same amount of mass overall. I.e. you keep more muscle losing 0.5 lbs a week over 40 weeks than 2 lbs a week over 10 weeks.
12 replies →
Can you provide a single high quality (randomized) study demonstrating GLP1 therapeutics are 'incredibly detrimental to [your] longevity and quality of life'?
Consider the type of confounding that occurs in studies of people losing a lot of lean mass: cachexia, restriction to bed, famine.
Traditional weight loss methods have not shown the magnitude of survival benefits wrt cardiovascular disease, joint pain, diabetic complications. Exercise is wonderful, but as a public health intervention it is not sufficient.
If anyone looks at the totality of the high quality GLP1 clinical evidence and concludes these drugs are going to cause a net reduction in longevity and quality of life, then they should step back and assess their process for evaluating information.
1 reply →
>>>Losing a lot of lean mass is incredibly detrimental to your longevity and quality of life.
While true, its also true that if you manage to lose substantial fat in the process, it leads to longer and better quality life
2 replies →
If I'm reading the study [1] correctly, that conclusion is not warranted.
It appears that they fed the control group and treatment group of mice lots of food to get them fat, then gave them identical normal diets, and gave the treatment group semaglutide.
The semaglutide group lost significantly more weight (fig A.ii) than the control group, and also lost heart muscle.
So it does not seem that they compared to an equivalent amount of weight loss in mice, which is what I'd think you'd need to do to come to the conclusion from the article (actually, not just an equivalent amount of weight loss, but also at the same rate).
[1] https://www.sciencedirect.com/science/article/pii/S2452302X2...
2 replies →
> 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...
Some years ago there was a crazy science exhibit going around museums in the US that had human cadavers preserved with some plasticizing process where you could see different tissues. They also had cross sections.
They actually had an exhibit showing the effects of obesity on tissues. This was before fat acceptance became a thing. That was really an eye opening exhibit showing shrunken muscle tissue, shrunken hearts, shrunken/squeezed lungs, etc.. in obese people.
Kind of opened my eyes as to how crazy the changes are.
3 replies →
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...
Meta comment here, but Science Direct is an aggregator, and it doesn't make sense to talk about it as publishing. Elsevier published the referenced work in the journal "Advances in Nutrition", vol 8, issue 3, pp. 511-519.
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.
The other thing is conflation between health and fitness. If you are below overweight range, no matter where you are, loosing additional fat is unlikely to make you healthier.
At some level of fat, which is actually more then "thin", you are perfectly fine. Further weight loss is about aesthetic or athletic performance, but has zero effect on health or even slight negative estimated health effect.
That doesn't strike me as a real problem.
Everybody already understands that "losing weight" means losing fat, not muscle. They don't leave the doctors office after a weight warning thinking they need to stop going to the gym.
Likewise, nobody is scared of gaining muscle because they think it will be bad for their health.
> 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?
Well, based on my DEXA scan from before I started on tirzepatide, if I had dropped to 20% BF with my starting LBM, I would have been in close to the best shape of my life. I certainly have a lot of extra muscle in my legs from carrying my fat ass around.
> Does more muscle mass indicate stronger muscles?
Yes. Strength for specific movements involves CNS adaptation, but if you look at the top tier of powerlifters, ranking them within a weight category by MRI muscle mass would produce basically identical results to their actual rankings.
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.
MouseLifts 5x5 + RAtkins diet
1 reply →
I'm always so baffled by people commenting without reading the article first.
> "Please don't comment on whether someone read an article."
https://news.ycombinator.com/item?id=42204741
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.
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.
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
This comes from professional bodybuilding, where people are using steroids, along with various, uh, interesting chemicals on the cut[1]. It has almost no benefit to (real) natural bodybuilders. It's closely tied to cycles of steroids.
[1] Ephedrine, Albuterol, Clenbuterol (literally only approved for horses in the US), DNP, and probably more that I haven't heard of. Here's an NIH article on the dangers of DNP, to put it in perspective: https://pmc.ncbi.nlm.nih.gov/articles/PMC3550200/
15 replies →
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.
[dead]
13 replies →
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.
> like its something against those facts above
I’ve seen multiple friends go from eating like shit, including chugging sodas, to not compulsively ordering dessert and no sodas in the house. I think all of them have since quit Ozempic, each seeing some rebound but nothing comprehensive and, most notably to your argument, not in the behaviour modifications.
22 replies →
> addicted to HFCS
HFCS consumption (along with added sugar consumption in general) peaked in 2000 and declined steadily until 2020: https://news.ycombinator.com/item?id=38094768
2 replies →
> (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.
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.
1 reply →
> For the people who lift weights while on this/these drugs, how much lean muscle do they lose?
I was 92kg when I started on liraglutide (I was doing GLP-1 agonists before it was cool!) and 67% of muscle mass (61kg). I'm now at 69kg and 82% of muscle mass (56kg). I'm doing weight and resistance training twice a week, in addition to aerobic training.
One nice thing, while muscles don't become more massive, they for sure become more pronounced and visible with weight loss.
5 replies →
I know 2 competitive athletes (both MMA) who experimented with it. Both came off of it within ~6 weeks because of complications, mostly related to mood (they got very, very temperamental on it). The athletes in my sphere know about it but aren't interested. The 2 who experimented have a non-trivial social media presence and, ultimately, that is what drove them to experiment.
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.
> 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.
I think it's a mistake to think of it as what people want. It's what people can do.
We have to acknowledge a fundamental struggle that we have with dieting and working out. Pretending it's just hard, when statistics show what is true at a societal level, will not bring us solutions.
We need something else. Either that's massive societal change to i.e. approach something like the diet/workout culture you have in Japan. That's hard. Or, as with many other of our health problems that we can't just will away, it's drugs.
Not believing in progress here, when drugs progress everywhere, is unnecessary. Current generations might have issues. Drugs will be better. We won't.
4 replies →
I don’t think anyone is disputing that changes to diet and exercise are required.
Based on people who I know have been taking these drugs, they make it much easier to reduce calorie intake by promoting satiety. That’s the benefit.
Doing the rest of your life while you feel hungry is not fun, and willpower is not infinite.
I don't know it is always avoidance when it comes to diet and exercise. I think oftentimes it comes down to overscheduling. I like to exercise, I like to eat healthy. Those two are oftentimes the first things on my chopping block when I am hurried
How has the gastric bypass affected this person? It would not have occurred to me that the brain would be affected.
2 replies →
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.
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.
The post you are replying to didn't say "always" it said "almost always," wich is perfectly cromulent. And it's also consistent with all the literature I have seen too.
Studies show strength training while losing weight can retain almost 100% of muscle.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5946208/
Anecdotally, it takes far less strength training than one would expect, too, to maintain muscle mass. From what I've experienced, 30 minutes a week, given sufficient stimulus, is enough.
2 replies →
Yep. I started resistance training 5x a week about a month in on tirzepatide and even with a severely restricted caloric intake (I just can't eat enough), I've gained LBM.
How did you measure the increase in LBM? This requires very advanced technical equipment. My suspicion is that you have noticed an increase in muscle volume and assumed it to be an increase in muscle mass. Those are largely due to water retention and increased blood flow. They revert quite quickly after you stop exercising for about a week.
5 replies →
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.
If someone is taking this medication for the right reasons, the risks of taking it are far lower than those associated with obesity and diabetes.
Also, concern of losing muscle mass on GLP-1 agonists (and diets in general) is well known and typically explained by the responsible MD to the patient.
I would be more concerned about the thyroid cancer when taking these drugs...
https://scholar.google.com/scholar?as_ylo=2024&q=glp+1+thyro...
The two meta-analysis are interesting, I think.
https://www.liebertpub.com/doi/abs/10.1089/thy.2023.0530
> Overall there is no conclusive evidence of elevated thyroid cancer risk.
https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/do...
> Our meta-analysis showed that GLP-1RA treatment could be associated with a moderate increase in relative risk for thyroid cancer in clinical trials, with a small increase in absolute risk. Studies of longer duration are required to assess the clinical implications of this finding.
It's potentially a possibility, but the absolute risk seems to still be quite low.
You did not lose 40 pounds of fat while building lean muscle tissue unless you're BOTH relatively new to weightlifting and use PEDs, in which case, the "hysteria" is justified for an average person.
Just the former is likely enough over a 6 month span, even without great genetics. That's only a 1.6lb/week loss. Noob gains can be huge.
2 replies →
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.
There is a dosing schedule for all the GLP-1s, with what is considered the minimal therapeutic dose being several times your initial dose.
However, a lot of people either see results on these initial doses, and plenty of people find them to be effective as maintenance doses.
1 reply →
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)
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.
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.
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.
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.
Tirzepatide (Zepbound) is double-acting but semaglutide (Ozempic) isn't. Both are prescribed for weight loss.
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.
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.
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.
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.
It says in the paper they used 21-week-old male C57BL/6 mice, as well as AC16 human immortalized cardiomyocytes
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.
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.
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=BX...
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!
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 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.
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
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.
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?
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.
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.
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.
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.
1 reply →
So... could this be a treatment for enlarged hearts?
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.
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?
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.
>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.
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.
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.
“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.
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.
> 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...
Then fund the stores through the Medicaid funds generated.
Gotta start somewhere.
1 reply →
> 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?
> So why don't you just eat healthier now?
I used to be you - in most of my 20s, I found it very easy to just eat well, east less, etc. It didn't take any willpower on my part to be fit. It was trivial. I didn't understand why fat people didn't just do the same things I was doing. I thought they had to want to be fat!
Then I got busy with other things, I had less and less free time, fast food, etc. got more and more convenient. Then the pandemic happened and I started just ordering uber eats twice a day. And suddenly I realized "holy shit, I'm fucking fat."
And then I tried to go back to my earlier habits, and it was hard. Things that took zero willpower on my part suddenly meant spending a significant portion of my day fighting different urges.
Was it within my power to do so? Sure, in theory. Everyone, given no other task to do but focus their willpower on just not eating too much, could likely eat healthier and lose weight. But that's not reality, it's difficult, and it ends up slipping down the priority list behind a dozen or two other things.
But on tirzepatide, my relationship with food nearly immediately reverted back to how it was when I was younger.
The fact of the matter is, America has a huge amount of obese people that know they shouldn't be and know in theory that fixing their diet and exercising would resolve their issues. And yet they still are fat. Very very very few of them want to be that way. And the reason is it is hard to just eat healthier when you have that level of food craving
2 replies →
"addictive" is an active word in the sentence you quoted.
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."
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.
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
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...
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.
1 reply →
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.
Can you tell if you're retaining muscle with that combination? Is this a doctor prescribed protocol or a DIY stack?
3 replies →
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.
How are bodybuilders getting a phase 2 trial drug still in development by Lilly?
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.
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".
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.
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
Perhaps--though worth keeping in mind that the overwhelming alternative is just lifelong obesity, along with all the negative impacts from that.
At least at a societal level, some increased rates of pancreatitis and a little suboptimal muscle loss are peanuts compared to what high obesity rates do to people at scale.
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.
2 replies →
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.
There's tons and tons of error checking- we have at least 5 different error correction and repair systems in DNA, cell cycle checkpoints, and extreme redundancy and feedback homeostasis at nearly every level. Every individual cell has it's own 4 copies of almost every critical gene- two of each chromosome made up of two strands of DNA each. Human bodies can function 70+ years, sometimes with no medical care- something no computer or man made complex machine comes close to.
Beyond specific diseases we understand, it's still mostly a total mystery why we aren't immortal- we have not yet identified what is the basic mechanism of aging, or why it happens at different rates in different species, and mostly our systems are fundamentally capable of repairing and regenerating almost anything, but for some reason get worse and worse at doing so over time. Moreover, this doesn't seem to happen in all organisms- there are many animals that live ~4x human lifespans, and at least one species of jellyfish that is biologically immortal.
2 replies →
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.
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.
Weight loss is not "off label" for this drug.
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."
Well, in vitro.
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).
> 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.
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
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.
If you’re 20% smaller, it would make sense that your heart could pump 20% less.
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.
> 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.
The next line of the article after that 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.
The rather obvious problem is that these GLP1 agonists don't improve your diet. If you continue to eat a protein and nutrient deficient diet (which is probably a majority of Americans) with caloric restriction on top of that, that leads to excessive muscle loss that you wouldn't see in a weight loss diet. This normally doesn't happen without GLP1 agonists, because these diets are too difficult to stick to for most people. Those who stick to them usually turn to nutritious high satiety whole foods that help combat the negative effects of caloric restriction.
Losing weight without losing muscle mass is very hard. It requires extreme diets like a protein sparring modified fast where 80%+ of your calories are from lean protein while running a 50% caloric deficit. If this research is correct, then using GLP1 agonists shortcuts the feedback loops that make the diets hard to stick to, but they shift the tradeoffs from weight to overall nutrition.
"When a measure becomes a target, it ceases to be a good measure" and all that.
> The rather obvious problem is that these GLP1 agonists don't improve your diet
My understanding from initial anecdotes is this is actually literally wrong. Which was surprising to me, too. But people on GLPs tend to prefer more nutritious food (high protein and high fiber). I'm not sure if this has been studied directly in clinical trials yet but I know that food manufacturers have been reorienting their products toward healthier meal configurations in response to the GLPs.
I predicted the exact opposite of this, but so far I appear to have been wrong.
13 replies →
>Losing weight without losing muscle mass is very hard.
I was with you up to here. In my experience it's easy to maintain a huge proportion of your lean tissue during a weight loss diet: Do some resistance training, get some protein, and don't lose weight too quickly.
There's no need to go to the extreme of a PSMF - which will still have you lose a bunch of muscle on account of being too big a deficit. If you can keep your calories reasonable while on a GLP1 agonist, there doesn't seem to be any reason you'll lose an exaggerated amount of muscle.
23 replies →
> If you continue to eat a protein and nutrient deficient diet (which is probably a majority of Americans)
Is it true the majority of Americans eat a protein deficient diet? I always thought there was too much protein in the western diet - nearly at every meals versus how we would have evolved with somewhat limited access.
2 replies →
I'm pretty skeptical of the "this rate of muscle decline is significantly higher than what is typically observed with calorie-reduced diets" claim. I suspect we're comparing apples to oranges rather than doing like-for-like comparisons at equivalent calories.
This is true. I just lost 30 pounds over 3 months and 17% was muscle. I thought I was eating a lot of protein, but I’ve upped it today.
I did an InBody scan the day I started (8/21) and just happened to have done my second one this morning.
1 reply →
I'd like to see the diets in the study that are specified as the "calorie-reduced diets". (Can't seem to find the paper). If it's the same as the Standard American Diet, this muscle loss is quite explainable. I think the mitigation is relatively easy though, if you want to shift the p-ratio, recommending a daily high protein shake would do a lot to stave off muscle loss (and even more if resistance training is applied of course). The exercise addition is probably the hardest to adhere to.
1 reply →
Lots of amateur body builders can do it. There are whole training guides about how to lose body fat, but maintain as much muscle mass as possible. Granted, they are probably a minority because they have higher discipline and motivation than the average population.
1 reply →
Losing glycogen stored in muscle is not a huge issue IMO, as it should come back fast. Stuff that's easy to gain is usually easy to lose and vice versa.
5 replies →
Nutrient deficient, sure, protein deficient? Probably not.
The claim that "a majority of Americans" eat a protein deficient diet is absurd on its face.
> Losing weight without losing muscle mass is very hard.
Yes it is.
> It requires extreme diets like a protein sparring modified fast where 80%+ of your calories are from lean protein while running a 50% caloric deficit.
I’m not any sort of expert but that sounds frankly, dangerous. I don’t see how you do something like that without damaging your liver.
It’s very possible to lose weight and gain muscle, but you have to be at just the right body composition (not lean and not obese) and then there’s a question of “over what period of time”?
Any duration under a month is probably pointless to measure unless you have some special equipment. Any duration over a month and it’s kind of obvious that it is possible. Eat a balanced diet without junk, work out regularly, and keep the calories to only what is necessary.
2 replies →
Part of the problem is that doctors recommendunhealthy diets and will dismiss healthy diets.
This is bullshit. Literally, I Googled for: what percent of americans have nutrient deficient diet?
First hit is some blogspam trying to sell me "Nutrient Therapy". Second hit is CDC: https://www.cdc.gov/nutrition-report/media/2nd-nutrition-rep...
Another thing that people frequently overlook, since post WW2, the US has been "fortifying" grains with essential minerals and vitamins. That means when people eat cereal and bread from the supermarket (usually highly processed), there are plenty of minerals and vitamins. Say what you like about the highly processed part, few are nutrient deficient.
1 reply →
Yeah, my four donuts per day fill me up just fine or an extra large milkshake and a burger and I’m done for the day with food is definitely happening for some people. Let’s wait and see these drugs might prove to be very beneficial and more testing definitely needed.
Americans eat a shit ton of protein. No idea where you got idea that from.
See the actual research article:
https://www.sciencedirect.com/science/article/pii/S2452302X2...
This study on mice was suggested by a previous publication:
https://www.thelancet.com/journals/landia/article/PIIS2213-8...
where it had been noticed that in humans "the 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", in comparison with muscle loss of only 10% to 30% when the weight is lost just by eating less, without semaglutide.
So with semaglutide, a larger fraction of the weight loss affects muscles than when the same weight is lost by traditional means.
While for other muscles the loss of mass may not be so important, the fact that at least in mice the loss also affects the heart is worrisome and it certainly warrants further studies.
> 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
Emphasis my own. In short: no evidence this is anything other than due to rapid weight-loss.
1 reply →
Interestingly, when I was part of a weight loss diet study at my local university I actually gained muscle whilst losing weight.
I had multiple full body dexascans during the programme.
I didn’t change my exercise routine at all. I wasn’t hitting the gym or doing weights, just my usual basic cardio.
And I gained muscle and lost ~10kilos in weight.
It wasn’t much muscle, but the amount of muscle was higher than before.
The latest research I’ve pulled suggests that DEXA scans are fairly inaccurate and aren’t a reliable way to measure body composition even for the same person across time.
MRI is the gold standard, everything else is pretty loosely goosey.
Sorry, no references but this comes up pretty often in the science based lifting communities on Reddit and YouTube if you want to learn more.
1 reply →
I don't have it at hand [edit: [0]] but there are a number of studies showing exercice had more health impact than weight loss (you can combine both of course, but just losing weight has less benefits)
As you point out, losing muscle is common in a diet, and the researchers are well aware of it. Their point was that this aspect is not pushed enough and is drowned by the losing weight part.
From the paper:
> Dismissing the importance of muscle loss can create a disconnect between patients' increased awareness of muscle and the role it plays in health, and clinicians who downplay these concerns, affecting adherence to and the development of optimised treatment plans.
[0] https://journals.lww.com/acsm-csmr/Fulltext/2019/08000/Effec...
For the "Fitness Versus Fatness" part for instance
The article does dissect the difference between weight loss drugs and dieting in general. Where they found that muscle mass loss was higher in those that took the drug as opposed to those who followed a calorie restricted diet.
To your point, the drug is absolutely to do with it if by taking the drug people need to be more mindful of the types of food they eat, if they have a smaller window to consume nutrients.
It is most certainly a contributor and for some who may not exercise like you, or consume an appropriate level of protein this research may show that those taking the drug need to focus on a more protein right diet.
Biology is super complicated with lots of surprising dependencies between different biological pathways. So it is possible. That said, I am skeptical as well. For example, if the body sheds 15% of its weight, does the heart naturally shrink by 15% as well? With so many people taking these drugs, there is enough data to begin to profile the rare risks of these drugs in humans (the clinical trials would have found any of the obvious risks)
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.
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.
6 replies →
I saw someone mention that they craved heroin less on ozympic.
Experiences vary but I worried I’d, like, not enjoy food on it.
Nope, not a problem. I just get full much faster and am even more prone to simply not eating when I’m busy, than I already was. Not as food-focused when idle, but I still snack a little or whatever.
Appetite comes back yes
It does.
god... 133kg down to 88kg, that's like a dream to me. Years of trying to get under 100 by 'traditional' calorie restriction diet & exercise.
One of my friends has tried many fad diets, etc. and he finally just went and paid cash for a GLP-1 and he's lost a lot of weight and is feeling much better. If I were in that situation, I would just do the same.
5 replies →
some fun study sort of concluded that the ratio carbs vs fat and protine is the entire mechanic. fat people who eat almost nothing eat only carbs thin people who can eat huge amounts every day eat a lot of fat and protein. Both eat other things just not as much.
1 reply →
So it smells like bullshit because of your personal anecdote? Or because some scientific evidence or experience you have?
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.
Ozempic can use their cash to start an exoskeleton division.
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?
This study is garbage. You can only trust what the companies that profit from the drugs publish.
There is no way magic weight loss pill with no side effects could possibly go wrong!!!
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.
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.
There's a linked article saying that 40% of the weight loss is muscle.
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.
6 replies →
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.
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.
There are no free lunches in nature.
Don’t care. I’m down 30lbs.
Who would have thought cheating to lose weight would have side effects?
The marketing is astounding.
"Weight-loss drug."
Oh, would that be Semaglutide?
<click>
Hey, would you look at that!
which weight loss drug?
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?
It is my own perception that HN has gotten worse in the six months but these sort of "meta" discussions can be as much part of the problem as part of the solution or possibly a bad smell.
My take it this.
The median scientific paper is wrong. I wrote a wrong paper. The average biomedical paper doesn't fit the standards of the Cochrane Library mostly because N=5 when you need more like N=500 to have a significant result. Since inflationary cosmology fundamental physics has been obsessed with ideas that might not even be wrong.
It's well known that if you lose a lot of weight through diet (and even exercise) you are likely to lose muscle mass. With heavy resistance exercise you might at best reduce your muscle loss if you don't use anabolic steroids and similar drugs. That you could have changes in heart muscle with using these weight loss drugs isn't surprising for me at all and it's the sort of thing that people should be doing research both in the lab and based on the patient experience.
(Funny you can get in trouble if you do too much exercise, spend 20 years training for Marathons and you might get A-Fib because you grew too much heart muscle instead of too little.)
A lot of the cultural problem now is that people are expecting science to play a role similar to religion. When it came to the pandemic I'd say scientists were doing they best they could to understand the situation but they frequently came to conclusions that later got revised because... That's how science works. People would like some emotionally satisfying answer (to them) that makes their enemies shut up. But science doesn't work that way.
The one thing I am sure of is that you'll read something else in 10 years. That is how science works.
The developers of these new peptide-based hormone-acting drugs like semaglutide(ozempic) could be called biohackers, but the system they're hacking on - the human endocrine system - is a delicate system. Introducing semi-synthetic mimics of native hormones can go wrong in all kinds of ways, and hormone-analogue drugs have a poor track record (anabolic steroids, DES, etc.) so extra caution makes sense.
Semaglutide is based on a 31-amino acid polypeptide that mimics the human GLP-1 hormone. At position 26, the lysine side chain is conjugated with a fatty diacid chain, to slow degradation and prolongs half-life, and there are some other modifications. However, the target - the GLP receptor - is not just expressed in the intestinal tract but all through the body, in muscle, central nervous system, immune system, kidneys and others. So some unexpected effects beyond the desired ones are likely.
Semaglutide was recently shown to have potent effects on the heart, and possibly beneficial to certain heart disease conditions associated with obesity. Makes me suspect this drug should be restricted to clinically obese cases where strong intervention with close medical supervision is needed. However for healthy people who just want to lose a relatively small amount of weight it really doesn't seem wise.
"Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization..." (June 2024)
https://www.nature.com/articles/s41467-024-48970-2
I agree with your desire for what HN should be, and disagree with your assessment that the top voted comment doesn’t support it.
HN is the only forum I know of that has broadly grasped that most so-called “science” outside of the hard sciences and mathematics is complete garbage and driven by funding needs. The world is awash in non-knowledge. This is an extremely serious issue.
Building the skill to rapidly come to a preliminarily judgement of a headline is crucial.
There is plenty of garbage in hard science too. Start with
https://arxiv.org/archive/hep-th
The most reliable source of knowledge we have are in the science. This is further reinforced by technological development that validated the sciences, although at time the technology may precede the science.
> disagree with your assessment that the top voted comment doesn’t support it.
Did you read the paper or skim its abstract, figures, and conclusion? I'm not so sure that commenter did, or they may have cited this,
> Because we report smaller cardiomyocytes in cultured cells and in mice treated with semaglutide, it is tempting to speculate that semaglutide may induce cardiac atrophy. However, we do not observe any changes in recognized markers of atrophy such as Murf1 and Atrogin-1. Thus, we cannot be certain that semaglutide induces atrophy per se or if it does, it may occur via molecular pathways that have not been identified herein.
> Building the skill to rapidly come to a preliminarily judgement of a headline is crucial.
You can't judge this paper based on the popsci headline.
> most so-called “science” outside of the hard sciences and mathematics is complete garbage and driven by funding needs
Based on my reading of the figures and conclusion, I don't think you should call this paper garbage.
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.
After I saw yesterday’s thread about politics in science was flooded with new sockpuppet accounts named after slurs spreading filth and downing everything they don’t agree with I no longer expect anything meaningful from comments here.
HN only works when you have a working assumption that people commenting here are smarter than you. It encourages respect and good faith engagement of content, instead of ad hom, concern trolling, and cargo culting.
It's been years since I've had that mindset when entering any thread above a certain number of comments.
I have noticed this too. The site guidelines say 'no low effort comments', but low effort comments that fit the general zeitgeist are often allowed, while well-thought-out ones that disagree are downvoted. If anyone has a suggestion for an alternative forum focused on technology and science, I really would love suggestions.
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.
I’m sure complaining about HN is as old as HN.
1 reply →
If you think HN users are normies, I think you might be in a bubble. Normies ain’t this literate.
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.
3 replies →
Yeah, normies suck. I totally only want to hear from people obsessed with the latest computer Science minutia!
For that reason HN should just remove the down/up votes, because it will turn this place to an echo chamber like reddit, these brownie points are useless.
What exactly do you think this forum is if you think this forum is above such sentiments?
Disagree. The “hacker ethos”, to me, is laypeople taking a crack at things without pretension.
Your comment lacks any substantive argument about the comment you complain about.
Apparently the topic is “important”. To me an appeal to importance when policing style spells like bullshit.
To be fair, that comment was about the claim:
> emerging research showing that up to 40 per cent of the weight lost by people using weight-loss drugs is actually muscle
Which is… obviously bullshit.
You lose muscle when you lose weight, especially if weight loss is rapid. This is why it's important to be physically active when you're losing weight. It doesn't matter if you're on drug or not.
they might have confused muscle and lean mass/FFM
The source article links to a reference for the 40 percent claim, which itself links to a couple articles that aren't available without a JAMA account.
I can't read the original sources there, but what makes you say its obviously bullshit?
6 replies →
[dead]
The cure for obesity isn't a pill.
Remember in the 80's and 90's when exercising and being healthy was considered a cool thing? Remember there was a gym on every corner and people were all about looking good and being healthy, eating healthy and living longer?
Then somewhere. . .
- We started normalizing obesity.
- We started this whole "body positivity" trend that celebrating morbidly obese people like Lizzo as positive role models was a good thing?
- We started introducing fat mannequin models in retail stores because being obese shouldn't have a stigma?
Obesity is a problem because we, as a culture have completely normalized obesity. Instead of promoting healthy diets and exercises and saying being obese has consequences like shortening your life and will make you susceptible to various diseases like diabetes and heart disease? All we've done is told people its ok to be obese and eat sugary drinks and over processed foods, because you can just have surgery and that will fix it. Or you can take a pill and that will fix it.
IT WON'T.
IT NEVER WILL.
We've gone down a road that is staggeringly dangerous because we've accepted being morbidly obese as something that's completely normal.
No, some chemical or chemicals got added to the environment around 1980.
All I can say is try losing 20 pounds and keeping it off for two years and how easy it is. Fat shaming might make a difference but I suspect it would be like knocking off 5 lbs from the average where you really need to knock off 50 lbs.
You only started seeing Victoria's Secret getting fat models in the last few years, the obesity epidemic on the other hand started in the Regan years. Maybe it's like taking your belt off when you get heartburn (though I know if I go that route pretty soon I'm going to need suspenders) Try
https://arxiv.org/abs/q-bio/0312011
for a theory that may be wrong but fits the chronology.
This is nonsense. The majority of the population don't want to be fat, ugly, and unhealthy and want to persists in maintaining good healthy habits in which they don't eat junk food.
People who promotes fat positivity are ridiculed.
Blaming it on culture overly simplify the issue, which is going to be a complex mix of interacting causes.
What are you talking about. Obesity was and still is something super common to make fun off for years.
In the 80, there was less stigma to being obese then now.
[flagged]
[flagged]
You do have to factor in the (probable) cost of not using Ozempic, aka keeping the pounds on. It may be imprecise, but as an example, if a person was likely to die within 10 years at their current weight, any bad effects beyond the 10 year mark have to be heavily discounted.
I assume parent was talking about cosmetic and convenient weight loss not medically necessary weight loss.
1 reply →
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.
On the other hand, being overweight takes years off your life:
"Specifically, we found that BMIs from 40 to 44 were associated with 6.5 years of life lost, but this increased to 8.9 for BMIs from 45 to 49, 9.8 for BMIs from 50 to 54, and 13.7 for BMIs from 55 to 59."
I think for some people the roi is measurable and reasonable.
https://irp.nih.gov/blog/post/2020/01/extreme-obesity-shaves...
Being obese takes years off your life. Being slightly overweight is associated with best longevity.
BMIs from 40 to 44 is massively obese, not overweight.
1 reply →
> If something sounds good too good to be true, it usually is.
You mean like antibiotics? Or vaccines?
> usually
I think this is superstition. Vaccines are a medical intervention that have almost zero downside. There isn’t some mythical cosmic cost-benefit scale that needs to be balanced in every new technology that is deployed.
Vaccines and antibiotics and germ theory are all things that seem “too good to be true” but nevertheless are. Should we be worried that clean fusion power, once commercialized and practical, is going to somehow cause some catastrophic unknown future event just because it yields immeasurable benefit to us?
I think this is just another form of magical thinking.
No one seems to remember Fen Phen or its stratospheric rise and fall https://en.m.wikipedia.org/wiki/Fenfluramine/phentermine
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?
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.
1 reply →
[flagged]
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.
K. But getting to a healthy weight by means of discipline and self control has a ~1% success rate[1]. That's dismal.
I wouldn't blame anyone for choosing the drugs over dying early.
[1] https://www.healthline.com/health-news/obese-people-have-sli...
If you find it hard to control your eating when you always feel hungry, taking a drug to reduce your feelings of hunger is self-control. It's exactly looking at your body as a system and controlling it.
Maybe you can titrate off the drug and in a perfect world, the hunger signal doesn't come back on all the time; that'd be great. Maybe, while on the drug, you've developed eating habits that you can continue while off the drug, even though you feel hungry all the time, again. Maybe, it's just too hard to ignore the hunger signal, and you need the drug for a lifetime.
That's not to say these drugs are necessarily wonderful. Previous generations of weight loss drugs came with nasty side effects that weren't immediately apparent. Fen-Phen was a wonder drug until it ruined people's heart valves. Stimulant appetite supressants have issues because they're stimulants. Cigarrettes have appetite supressant properties (not surprising, nicotine is a stimulant), but they're cigarettes.
Personally, I don't have an overactive hunger signal; so when I eat poorly and gain weight, it's on me. But other people I know have a totally different experience with hunger. If your body is telling you all the time that you need to eat, it's hard to say no. Just like it's hard not to scratch when your skin is itchy. I can resist itchyness sometimes, but when it's constant, I'm going to scratch.
Yeah, I am sceptical, but we'll have to see how it pans out.
Vanishingly few people succeed in exercising discipline and self-control long term. But obesity is caused by food addiction and the idea is once you've kicked the addiction and got over the withdrawal etc then it's gone and you no longer have to fight it. I don't "exercise discipline" to stay thin. I just don't eat copious amounts of junk food because I'm not addicted to it.
So if the drugs are used to soften the withdrawal symptoms such that people can learn to like real food and kick the addictive crap then that's good. But if they're used as a magic pill with no other lifestyle changes then I'm sure people will just go back to what they were doing before once those pangs come back.
I'd still rather we went after the industry peddling the addictive shit. We went after the cigarette companies. But food companies seem untouchable.
So why not just stay on the drugs?
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.
3 replies →
$$$
Most kill you. If I didn't misread articles on ozempic, they can cause digestive problems where food rots in your stomach. Bad depression was another side effect which blows my mind since you'd think looking better would make you feel great. And these were the minor things.
10 replies →
I like how they aren't saying Semaglutide in the title in an attempt to perhaps keep it from immediate scrutiny.
The first link goes to the study and it does mention the ingredient: https://www.sciencedirect.com/science/article/pii/S2452302X2...
I am talking about UAlberta's title specifically.
1 reply →
More likely because the average reader won't know what that is versus the current title which succinctly summarizes it.
https://www.fda.gov/drugs/postmarket-drug-safety-information... Same thing??
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.
> 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".