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

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?

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 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 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.

What exactly do you think this forum is if you think this forum is above such sentiments?

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.

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.

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.

they might have confused muscle and lean mass/FFM

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 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?

From my observation it is hard to get to 501 karma points by the karma gained from submissions than through comments. So for comments every 1 upvote equals 1 karma. But for submissions, god only know what is the conversion rate /s. I think there are many factor. But I think this mechanism is to limit people creating accounts and mass down voting anything they don't like. So it is trying to solve another problem. However upvote power should be limited for new accounts (I don't know if this already the case)

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.

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.

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.

I’m sure complaining about HN is as old as HN.

There is plenty of garbage in hard science too. Start with

https://arxiv.org/archive/hep-th

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.

Yeah, normies suck. I totally only want to hear from people obsessed with the latest computer Science minutia!

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

Specifically comparing HN to reddit is old as well. It's mentioned in the guidelines to not say HN is turning into reddit. The examples of this shared in the guidelines go back to 2007

> 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.

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.

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 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.

If you think HN users are normies, I think you might be in a bubble. Normies ain’t this literate.

From the abstract:

"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."

The "surprising" part is kinda bullshit, and implies there's something special about glp-1s. It is the opposite of surprising that weight loss includes a lean mass loss.

That said, being skinnyfat is probably bad for you and the idea that you should work to preserve/build muscle and not only lose weight is a good one.

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.

FFM isn’t entirely muscle, but what other weight would be shed when losing FFM other than muscle?

> FFM isn’t entirely muscle, but what other weight would be shed when losing FFM other than muscle?

I'm not an expert, but I have to imagine that most of it is muscle.

After dramatic weight loss, a person will probably lose some bone - particularly in the lower body - due to decreased loading.

I know body builders sometimes eat extremely high protein diets (more than 1 g/lbs of body weight) and lift quite hard to try to hang on to as much muscle mass as possible. And they still lose some when cutting.

Water weight is a big one, and is part of your FFM. I lost 10lb of water weight in my first 24 hours on tirzepatide.

Some of it is likely bone density as well. You can prevent the bone density and muscle loss with proper diet and exercise, though.

I might be biased in my perspective because I tend to focus on links that make it to the front page. It's true that many links end up languishing in obscurity.

I just think the level of effort involved is different. For instance, the person who posted the link to the study we're now discussing earned 199 points with far less effort than you put into replying to my comment. Many of the links posted are copied from Reddit, Twitter, Slashdot, etc.

I am sure what he actually got is much less than that number. If you got 200 up votes to a comment then that's 200 karma, but with submissions it is different, maybe dang can shed some light on that. Also what gets traction depends on a lot of things that you will find that most people will have the vast majority of their submissions have little to zero activity. So it is not that easy, some will manage to do it but the purpose is to limit that to something manageable. Then I think dang is managing both up voting ans down voting rings. With up voting being harder (everyone can do that)