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

105 points2 hoursualberta.ca
cm21872 hours ago

> emerging research showing that up to 40 per cent of the weight lost by people using weight-loss drugs is actually muscle

That's the sort of headlines that smells like bullshit to me.

My understand of those drugs is that they don't actually make you lose weight, they just cut your appetite so you can follow a diet to lose weight without hunger hammering at the door. So to start with, if that's the case, all they are observing is the effect of a diet. Not sure the diet drug has much to do with it.

Then I went from 133kg to 88kg with these diet drugs. Even though I exercised every day, I am sure I also lost some muscle mass as well, just because I don't have to carry 45kg every time I make a move anymore. Seems logical and would probably be concerned if it was any other way.

throwup2382 hours ago

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.

llamaimperative1 hour ago

> 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.

throwup2381 hour ago

I’ve heard that anecdote from HN users many times but based on my meatspace social group of (mostly) California yuppies, that effect is vastly overstated. Even some of the diabetics I know on Ozempic have started using it as an excuse for a shittier diet. Now my sample size is barely ten people on Ozempic/Wegovy so take it with a grain of salt and what not, but I’m skeptical.

I bet there’s a large group of people - possibly over represented on HN and other online communities - that just need a little nudge to suppress their cravings and eat healthier, but that’s far from universal. For a lot of people, they wouldn’t even know where to start to eat healthier except choosing a salad over a burger at the takeout menu. Even with drugs masking cravings, many people just haven’t had good health or culinary education.

burnt-resistor22 minutes ago

I take mirtazepene because it's the only antidepressant that works for me; unfortunately, it's also a massive orexigetic. And also unfortunately I have original Medicare that doesn't cover semaglutide until I develop additional heart problems or diabetes, so I'm forced to buy compounded semaglutide for 10% of the retail cost (but still higher than the rest of the world) out-of-pocket from a local large, retail, independent pharmacy that wouldn't risk bankruptcy selling fake medications.

And I don't eat meat for non-dietary reasons that include existential risks to all of humanity:

- Pandemics - Where did the "Spanish" flu (and influenza A, Asian flu, HK flu, and 2009 pandemics) and COVID come from?

- Antibiotic resistance - Most classes of antibiotics used in humans are also used to make industrially-farmed animals grow faster, leading to greater antibiotic resistance and more potential bacterial pandemics too

- Climate change - 17%, at least

- Air pollution - Not just the smell of pig crap in the air

- Water pollution - Ag runoff has been ruining river delta systems

- Soil pollution - (It's gross)

- Fewer available calories for total consumption

- More expensive foods by less supply and more demand

(Never bother with "meat is murder" dramatic preaching because most people who eat meat suffer from cognitive dissonance preventing them from admitting their lifestyle choice causes animal cruelty.)

When I was on and could afford semaglutide, I improved my diet by consuming a high protein product with a low calorie breakfast nutrition supplement. I'm sure I probably could've accomplished similar with a multivitamin and a protein product. What I need to change is eating more low calorie, high fiber fruits and vegetables that don't taste like cardboard or a mowed lawn. My diet has gone to shit again because the insatiable, all-consuming (no pun intended) hunger has returned.

+2
llamaimperative1 hour ago
throwaway203745 minutes ago

This observation is very interesting. I hope that it is studied more closely and we can read some peer reviewed research on the matter. One idea popped into my head: Could part of the cause be that people's mood and self-esteem improves during (GLP1 agonist-induced low hunger) weight loss? TL;DR: If you feel like shit about yourself (and body), then you are more likely to eat poorly, and vice versa.

llamaimperative41 minutes ago

That's an excellent hypothesis. Wouldn't be surprised at all if that was a component!

voisin35 minutes ago

> 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.

dgfitz31 minutes ago

So, lots of foraging for food that grows on plants and the occasional bison?

Would that we could convert the world to diets like that.

whythre24 minutes ago

A lot of what Americans consume is really crappy carbs and sugar, unfortunately. Even fatty meats would be better than that.

zemvpferreira1 hour ago

>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.

twelve401 hour ago

> In my experience it's easy

> Do some resistance training, get some protein

jeez, if people actually did that they wouldn't need the drug to begin with

throwaway203737 minutes ago

I must disagree with your comment. Personally, I have witnessed so many people struggle for years with their weight. Being overweight and struggling to lose weight must be a 50 factor model: Multiple social, economic, and mental/physical health factors. These GLP1 drugs really are a game changer.

turbojet132147 minutes ago

It's notoriously hard to lose fat without also losing muscle. That's why bodybuilders bulk well past their target muscle mass before they cut for competition. I agree that you can do a lot to mitigate it through protein intake and resistance training, but you'll almost certainly still lose muscle when you're in caloric deficit, regardless.

throwaway203739 minutes ago

I'm not sure why this is so heavily downvoted. You raise some good points. I would add: The era of comical bulking is coming to an end. More and more scientific literature points to modest calorie surplus is the key to muscle gain (along with regular weight training).

phil211 hour ago

Bodybuilders I know seem to have a a very difficult time keeping their muscle gains while on a cut, I don’t know why someone who is not in a gym 5+ days a week and on an extremely optimized heavy protein diet measured down to the gram would expect otherwise.

Is it possible to go very slow and keep most of your lean muscle mass? Sure. Is it practical? I have my doubts.

Part of the effectiveness of these drugs - for me at least - is that results are rapid and that is a self-reinforcing feedback loop. Diets that had me losing 1lb/week were simply too boring and unmotivating for me to keep up beyond a few months. A few days of vacation “cheating” and you wipe out a month or more of incredibly difficult to achieve loss. Restricting yourself mentally in what you eat every day adds up to exhaustion over time.

Some folks can manage to lose very slowly while also adhering to a strict calorie deficit of a few hundred per day, while also being consistent with resistance training. I’d say the evidence shows that these folks are in the small minority.

I will say more evidence is needed for this drug class - especially where the harm reduction principle may be a bit iffy outside of obese folks. However it was life changing to me in the way it let me change my eating habits to very healthy protein and veggies as my primary calorie intake, as well as made going to the gym on a strict schedule motivating enough to actually come out at the end with a better bodyfat to lean muscle ratio than where I started.

These gains have continued since I hit my goal weight - and now I’m starting to become one of those folks who the BMI no longer applies to in a good way. I do wish there was a good way to test heart muscle mass like there is lean body mass with a DEXA scan as I’m curious if my increased regular workout heartrates translates into building back any heart muscle mass like it did other lean muscle. Certainly a concern to keep an eye out for!

I’m curious as you are if folks who are slow responders and live active lifestyles see the same muscle loss the hyper responders do. For reference I lost over 100lbs in just under 9mo. I absolutely lost considerable muscle mass, but have since put it back on and then some.

ohyes50 minutes ago

I feel like a cut is a very specific type of weight loss where the person gets down to an unusually low body fat %. It’s to the point where each bit of fat loss is a significant portion of your body’s fat reserves. It seems different from when there is an abundance of easily accessible fat to burn.

kbos8743 minutes ago

It isn't hard to imagine that the last 10% of mass a bodybuilder has added was hard won and easily lost. That isn't representative of most people.

Kirby641 hour ago

For the average overweight person? I disagree. The average obese person does little to no resistance training, eats very little protein, and wants to lose weight fast so they're not paying for expensive GLP1 drugs for a long period of time.

You're asking folks to make three separate changes: start exercising, change their diet to add protein, and use GLP1s to reduce food amount. And reducing food amount already goes against adding protein, so whatever protein they were getting is going to get cut even further.

astrange1 hour ago

Increasing exercise also goes against reducing food amount, because it makes you hungrier.

XorNot1 hour ago

I mean when I needed to lose weight (15kg, 85kg -> 70kg) I started with calorie restriction, and as a result of that actually looked at what I was eating and realized I was incredibly low on protein, and then from that added some daily light exercise partly just to avoid getting bored and wanting food.

So this isn't really 3 separate unrelated changes. Also at least in my experience, people tend to regard high protein things as the "energy dense" part of a meal - the problem with a lot of carbohydrates is they're not very filling.

The biggest problem with exercise is it's an awful way to lose weight - you don't burn that many calories, it makes you hungrier, and then your body optimizes to burn even less calories as you do it.

hehehheh1 hour ago

Intuitively, if you can lift a modest bench press (not novice, maybe beginner-intermediate) and you keep training and you consume a few fewer calories (not starve) why would you lose your strength.

Panzer041 hour ago

Because the body does not make it easy to keep the same muscle with less fat.

For most people, it just doesn't really matter, because their strength is so far below their peak capability it won't be hard to cut some weight while maintaining strength. The closer you get to the edge of capabilities, though, the more it will matter.

loeg2 hours ago

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.

throwaway203743 minutes ago

    > 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.
pottertheotter1 hour ago

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.

sheepscreek38 minutes ago

I don’t think we can expect to retain 100% of muscle mass, and losing just 1/5th sounds like a good outcome.

I’ve understood that generalizing anything in today’s time is a losing game. I know many people with IBS/GI issues and I am also sure they have different underlying causes. Our gut biome and how digestion works in general needs to be researched much more.

I don’t know why progress has generally been so slowly on that front. For instance, GLP-1 was discovered in the 1970s. It took us another 40 years to commercialize it in the form of Semaglutide and another 10 years to get it ready for human consumption.

ipsento60634 minutes ago

The claim that "a majority of Americans" eat a protein deficient diet is absurd on its face.

chunky19942 hours ago

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.

groby_b1 hour ago

I'd be surprised if either mice or human cells eat "the Standard American Diet"

uxp10042 minutes ago

Nutrient deficient, sure, protein deficient? Probably not.

ohyes1 hour ago

> 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.

throwup23828 minutes ago

> 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.

I haven’t seen any credible research that a healthy person can damage their liver from excessive protein intake. Someone suffering from liver disease needs to be careful, sure, but evidence that it would harm a healthy liver is practically nonexistent.

That said, PSMF is explicitly not a sustainable diet and proponents generally don’t claim it to be. It’s a short term diet meant to preserve muscle mass under extreme caloric restriction (under 1.2k calories).

> Eat a balanced diet without junk, work out regularly, and keep the calories to only what is necessary.

If it were as simple as that, we wouldn’t be having this conversation.

throwaway203748 minutes ago

    > nutrient deficient diet (which is probably a majority of Americans)
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...

    > 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.
andy_ppp1 hour ago

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.

bongodongobob31 minutes ago

Americans eat a shit ton of protein. No idea where you got idea that from.

adrian_b2 hours ago

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.

petesergeant1 hour ago

> 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.

makeitdouble1 hour ago

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

firecall2 hours ago

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.

philipbjorge2 hours ago

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.

jostmey1 hour ago

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)

denkmoon2 hours ago

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.

renewiltord1 hour ago

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.

twelve401 hour ago

bringing it down is not even half the battle, it's what happens next is the more interesting part

turbojet132139 minutes ago

You keep taking the GLP1 agonist, otherwise you gain the weight you lost.

throwaway143562 hours ago

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.

colordrops1 hour ago

So it smells like bullshit because of your personal anecdote? Or because some scientific evidence or experience you have?

taeric2 hours ago

Yeah, folks don't like thinking that obese people have a lot of muscle needed to move around. And losing weight is losing all weight.

hnthrowaway03282 hours ago

Just curious, does your appetite come back whence you cut off the meds?

The only reason I want to lose weight is to eat more freely, won't be useful if I lose my appetite too.

cm21872 hours ago

You don't lose taste, you lose your appetite, which means you can resist the temptation to eat easily, and you feel full very quickly. That doesn't prevent you from eating what you like, but it does help you to not eat too much of it, which I hope is not what you mean by "more freely".

The appetite comes back when you cut the meds, but it's an appetite based on your new weight. But if you then go on a some suggar rampage, you will regain weight and your appetite will grow too.

Those drugs are merely a guard rail to complete a diet successfully, but if people do not change their eating habbits, the same causes will produce the same effects after they cut the meds.

andy_ppp1 hour ago

What I’ve found is foods I could usually binge on like pizza I’m quite full on GLP-1 inhibitors and can quite happily stop at half or 2/3 of a pizza. Usually I’d have eaten the whole thing (12” think napoleon style pizza Americans) and want more, refined carbs I never feel full from.

hnthrowaway03282 hours ago

Thanks, that's good enough. I have been going to weight loss for over 6 months but I'm stuck between 79 and 80kg. It's a bit difficult to add more weight lifting because I tended to hurt myself, so eat less is better.

throwaway203729 minutes ago

    > It's a bit difficult to add more weight lifting because I tended to hurt myself
Did you try slightly lower weight and higher reps? It is worth trying as an experiment. Current scientific literature says that 5-30 reps is the ideal range for gaining muscle mass. And, as you said, the relative heaviness of weights to the person makes a big difference for injury risk.
andy_ppp1 hour ago

Add walking for 2h per day is the recommended I’ve seen.

xeromal2 hours ago

I saw someone mention that they craved heroin less on ozympic.

0xB31B1B2 hours ago

Appetite comes back yes

andreareina2 hours ago

It does.

talkingtab39 minutes ago

It concerns me how discussions, such as this one go on HN. This is an important topic. With the epidemic of obesity we now find a drug that appeals to a large number of people. This is an important topic as well.

What is the current comment receiving most of the comment?

"That's the sort of headlines that smells like bullshit to me"

That's the sort of comment that smells like bullshit to me. What kind of place is this?

Many times I find the posts on HN interesting, but increasingly these kind of comments make me wonder about Y Combinator. Is this really the best they can do?

And for us readers who are supposed to be so called hackers, is this the best we can do?

throwaway203727 minutes ago

I agree 100%. Those kinds of comments have no place, and add little to nothing to the discussion. Many HN discussions outside of pure tech invite all kinds of crazy and uninformed comments -- health/diet, finance/economy, etc.

delichon2 hours ago

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

acyou55 minutes ago

The study found that heart muscle decreased in both lean and obese mice. So any observed muscle loss might not be just from losing body mass and not having to work as hard.

But if you're already lean and then go on a calorie deficit (as a result of decreased appetite from taking the drug), then muscle mass will be lost through metabolism of muscle and other tissue.

Then the study states further that the proportion of muscle loss is higher than expected from calorie restriction alone.

My gut feeling here is that where there's smoke there's fire, and I predict dramatic class action 40 years in the making, either like tobacco, or like baby powder, depending on the actual long term health outcomes.

And, this is great research! We need more like this ASAP!

et2o31 minutes ago

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

jyscao1 hour ago

When Ozempic started making the rounds in the news with glowing reviews, my instincts told me there likely was some long term negative effective that wasn't immediately apparent yet.

If something sounds good too good to be true, it usually is.

jmward011 hour ago

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

GenerWork55 minutes ago

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

wizzard02 hours ago

well that's a weight reduction too!

on a more serious note, could it be that the load on the muscle gets lower so they adjust?

8% reduction for 30% body weight reduction sounds reasonable to me at first glance

bastawhiz1 hour ago

The research says

> Together these data indicate that the reduction in cardiac size induced by semaglutide occurs independent of weight loss.

Which does sound concerning. It's the drug, not the weight loss, that causes the muscle loss.

I guess the question is whether it's better than nothing. Is the loss in lean muscle a worse outcome than remaining obese?

LeoPanthera2 hours ago

It's my understanding that if you have hypertension, your heart muscle grows thicker as a consequence of working harder against your blood pressure, which reduces the flow capacity of your heart.

So if you have hypertension, this might actually be a "good" side-effect?

httpz2 hours ago

Some of the side effects of semaglutide are just a result of eating less calories.

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

quantumwoke25 minutes ago

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

loeg2 hours ago

So like, it's interesting that this happens in mice, but we did not see increased heart disease in human RCTs of these drugs.

Maybe the mouse dose is just absurdly high? "Mice were then administered semaglutide 120 μg/kg/d for 21 days." That could be vaguely reasonable -- human doses range from, idk, ~36 to ~200 μg/kg/d (2.5mg/week to 15mg/week at ~100kg).

DidYaWipe2 hours ago

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

PlunderBunny2 hours ago

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

loeg1 hour ago

Well, in vitro.

CyanLite21 hour ago

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

dgfitz34 minutes ago

Uh, I think most highly in/shape people have normal sized, very healthy hearts and their bpm is like 45.

Their hearts are not physically smaller, nor did they shrink during their build-up to current physique.

Saying things like this is harmful at best. Please don’t.

xyst2 hours ago

folks, this is why I lean on skepticism in regards to “off label” usage (ie, weight loss).

Have only lived a few decades on this planet and the weight loss trends with pharmaceuticals is wild.

akira25011 hour ago

The marketing is astounding.

"Weight-loss drug."

Oh, would that be Semaglutide?

<click>

Hey, would you look at that!

wileydragonfly1 hour ago

Don’t care. I’m down 30lbs.

dyauspitr43 minutes ago

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

polishdude202 hours ago

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

derektank2 hours ago

From the commentary,

>Studies suggest muscle loss with these medications (as indicated by decreases in fat-free mass [FFM]) ranges from 25% to 39% of the total weight lost over 36–72 weeks. This substantial muscle loss can be largely attributed to the magnitude of weight loss, rather than by an independent effect of GLP-1 receptor agonists, although this hypothesis must be tested. By comparison, non-pharmacological caloric restriction studies with smaller magnitudes of weight loss result in 10–30% FFM losses.

Comparing weight loss of different magnitudes is kind of comparing apples to oranges. Of course, it's not really possible to get persistent, large magnitude weight loss any other way than by using these drugs, so I understand why the comparison was made.

sfink2 hours ago

There's a linked article saying that 40% of the weight loss is muscle.

com2kid2 hours ago

Outside of cardiac muscle, which is a bit worrisome, 40% of weight loss being from muscles is incredibly typical for any diet that sheds pounds.

There are very complex dietary regimes that can be followed to minimize this, but most studies have shown that they don't save any time compared to losing weight and then working to get the muscle back afterwards.

> Dyck’s study comes on the heels of a commentary published in the November issue of The Lancet by an international team of researchers from the U of A, McMaster and Louisiana State University who examined emerging research showing that up to 40 per cent of the weight lost by people using weight-loss drugs is actually muscle.

This is, again 100% typical of what happens with caloric restriction.

throwup2382 hours ago

Literally the next line after the 40% quote:

> Carla Prado, a nutrition researcher in the Faculty of Agricultural, Life & Environmental Sciences and lead author on the commentary, explains this rate of muscle decline is significantly higher than what is typically observed with calorie-reduced diets or normal aging and could lead to a host of long-term health issues — including decreased immunity, increased risk of infections and poor wound healing.

Do you have a source that 40% muscle loss is typical for a caloric restriction diet without GLP1 agonists?

loeg1 hour ago

> There are very complex dietary regimes that can be followed to minimize this

The dietary regime isn't complex -- just consume a LOT of protein. Something like 1-2 g/kg/d. And non-dietary: do strength training.

devmor48 minutes ago

Yep, I can anecdotally confirm as I’m on such a routine right now.

I started losing weight from severe obesity with a caloric deficit but noticed I was also feeling weaker in general (aside from the tiredness that comes with eating under your TDEE).

I started going to a trainer and he had me change my macros so that I was consuming about 200g of protein per day in addition to 4 days per week of full body workouts on top of my cardio.

Since then I’ve lost an additional 150% of my initial weight loss, and have gained moderate muscle mass on top of that.

ramesh3145 minutes ago

>My understand of those drugs is that they don't actually make you lose weight, they just cut your appetite so you can follow a diet to lose weight without hunger hammering at the door.

While acknowledging that the mechanism is different, this was the same effect of Ephedrine, which went through a similar craze as Ozempic before the full complications were known. My bet is that this will be similar, where the risks end up being outweighed by the benefit for extreme obesity and diabetics, but that the cosmetic weight loss aspect of it will become outlawed or highly regulated.

renewiltord2 hours ago

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

oksurewhynot1 hour ago

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

jongjong2 hours ago

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

kylehotchkiss2 hours ago

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

moduspol1 hour ago

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.

jongjong1 hour ago

Yes 100%. That's why I never understood the rollout of MRNA vaccines during COVID. It's like pushing a massive code change straight to production during peak traffic and without the normal phased rollout. I totally understand where conspiracy theorists are coming from. That didn't seem right.

kylehotchkiss1 hour ago

yeah, it's too bad the tech didn't have a better way to gain peoples trust (through some other breakthrough with the normal set of clinical trials). I think the solve was impressive (tell cells to produce a protein that looks exactly the same as the viruses and place it outside the cell to piss off antibodies) but protein-protein interaction data is hard to come by. Maybe these guys can figure it out https://www.aalphabio.com

akira25011 hour ago

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

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

UniverseHacker1 hour ago

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.

akira250129 minutes ago

Redundancy is not error checking. The "error correction" mechanisms are actually just "proofreading" mechanisms and are almost entirely local and centered around transcription. Common mode errors are harder to induce due to the plain redundancy of DNA pairs but also not impossible, and once induced, are impossible to locally notice or correct. In some cases the "error correction" machinery is the cause of these induced errors. The result is genetic disease and/or cancer and is a case of missing error _checking_. Perhaps my definition was exceptionally parsimonious.

> with no medical care [...] something no computer or man made complex machine comes close to.

That's because we get far more units of "work" out of our machines than the person living for 70 years with "no medical care." Some people live just 30 years with no medical care too. And the machine does not need to sleep. We eat food they eat lubrication oil. I don't think this was a good analogy.

> it's still mostly a total mystery why we aren't immortal

While we haven't pinpointed the mechanism, we have a pretty good idea of why, and where in the system we should be looking for the answers.

> but for some reason get worse and worse at doing so over time.

You are a living Ship of Theseus and these "error correction" mechanisms are not perfect. Aside from this there are known genetic disorders which alter the rate at which people age. This is not nearly as mysterious as you're making it out to be.

> there are many animals that live ~4x human lifespans

And what are their resting respiration rates?

> and at least one species of jellyfish that is biologically immortal.

In theory. We haven't found an immortal one yet. They all die. They're also nowhere near our level of biological complexity or capability.

GauntletWizard2 hours ago

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.

therein2 hours ago

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

rzzzt2 hours ago

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

therein2 hours ago

I am talking about UAlberta's title specifically.

rzzzt2 hours ago

"Semaglutide Reduces Cardiomyocyte Size and Cardiac Mass in Lean and Obese Mice" was also written by UoA researchers. I don't see anything nefarious in the choice of the title for the news blurb.

skeaker2 hours ago

More likely because the average reader won't know what that is versus the current title which succinctly summarizes it.

TylerE2 hours ago

No. That’s talking about the compounded versions (NOT in an auto pen) that were temporarily allowed due to shortages, but whose authorization has since been revoked.

therein2 hours ago

> Unapproved GLP-1 Drugs Used for Weight Loss Yeah that would be perfect. But editorializing it to the point of calling it `weight loss drug`, just feels like it is begging for the reaction of "oh yet another weight loss drug".