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

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

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

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

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

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

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

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

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

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

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

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

I wondered about exactly this.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

> (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.

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.

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.

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.

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.

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

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

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

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.

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.

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.

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).

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.

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.

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...

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)

> low dose of Semaglutide

I thought its only approved at standard dose.

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

I tried taking it for IBS for that reason.

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

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

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

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

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

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

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

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

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

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 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.

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.

> 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"

So why don't you just eat healthier now?

> 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...

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

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.

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

> 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.

If found the opposite to be true.

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

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

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

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

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

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

Well, in vitro.

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

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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 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 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.

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.

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

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.

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.

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.

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.

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.

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.

The first link goes to the study and it does mention the ingredient: https://www.sciencedirect.com/science/article/pii/S2452302X2...

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??

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.

So why not just stay on the drugs?

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.