HN Reader

I'm always so baffled by warnings about losing muscle when losing weight.

Of course you do! If your body is tens of pounds lighter, then you don't need the extra muscle to lug it around. This paper is about reduction in heart muscle, and of course your heart doesn't need to be as strong because there's less blood to pump and less tissue to fuel.

When you gain weight, you also increase the muscles needed to carry that weight around. If you see someone obese at the gym doing the leg press, you may be astonished at how strong their legs are. When you lose weight, you don't need that muscle anymore.

Our bodies are really good at providing exactly the amount of muscle we need for our daily activities (provided we eat properly, i.e. sufficient protein), so it's entirely natural that our muscles decrease as we lose weight, the same way they increased when we gain weight. Muscles are expensive to keep around when we don't need them.

Obviously, if you exercise, then you'll keep the muscles you need for exercising.

But this notion that weight loss can somehow be a negative because you'll lose muscle too, I don't know where it came from. Yes you can lose muscle, but you never would have had that muscle in the first place if you hadn't been overweight -- so it's not something to worry about.

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

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?

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

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

I 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.

I'm not commenting specifically on the heart-muscle aspect of the study, but it shouldn't be a surprise that the weight loss from this drug is significantly attributable to muscle loss; it almost always is when dieting. It's the same with keto/low-carb or any other kind of caloric-restrictive dieting (which Ozempic facilitates).

The modern weight-loss programs I'm seeing now (at least those aimed mostly at middle-aged men) emphasize consuming significant amounts of protein (2g for every 1kg of body weight each day) and engaging in regular resistance training, in order to maintain muscle mass.

The article addresses this:

To keep muscle strong while losing weight, Prado says it is essential to focus on two main things: nutrition and exercise. Proper nutrition means getting enough high-quality protein, essential vitamins and minerals, and other “muscle-building” nutrients. Sometimes, this can include protein supplements to make sure the body has what it needs.

Perhaps there needs to be more formal research into this, and a strong recommendation made to everyone using these drugs that this kind of diet and exercise plan is vital.

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

It's pretty clear that GLP-1 should be prescribed with protein powder. When your appetite is crushed you don't go for the chicken breast, you go for what is immediately appetizing (usually carbs+fats like pizza or fries). IMO this and a lack of resistance training (which should also be prescribed) probably makes up a large % of the muscle loss on these drugs. The problem is that the FDA only looks at dumb measures like weight lost, not body fat % when approving these drugs.

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

There are a lot of people here citing loss of muscle mass as a side effect of GLP-1s, when the reality is that weight loss almost always comes with muscle loss.

For me, that hasn't even been the case. I'm down 40lbs on a relatively low dose of Semaglutide and my muscle mass has moderately increased over the last 6 months. The hysteria over this is totally unfounded.

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.

“Dyck, who is the Canada Research Chair in Molecular Medicine and heads up the Cardiovascular Research Centre, says his team did not observe any detrimental functional effects in hearts of mice with smaller hearts and thus would not expect any overt health effects in humans.”

This makes sense. If fasting hurt your heart many of your ancestors would have died early. There is strong selection pressure to survive extended fasts.

I 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.

I was wondering when the other shoe would drop.

These drugs are turning into a band-aid on the fact that it's more profitable to sell addictive, high-calorie foods in the US than foods that promote long-term health.

We'll decay people's heart muscles before we put a tax on unhealthy food to help fund Medicare and Medicaid.

I used Ozempic for couple months. I lost 25kg over 6 months (120kg -> 95kg).

I gained muscle, as I started weightlifting (modified 5x5 program 3-4 times a week) and was supplementing with protein isolate (about 50g a day).

My subjective feeling is that even if "Ozempic makes you lose muscle faster than the same caloric deficit without it" is true, this effect is very small.

Vast majority of muscle loss comes from no resistance exercise, low protein, much faster weight loss than possible "naturally".

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.

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.

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

To reply to a now deleted comment about weight loss:

You will still lose "muscle", and some of that will be in the fat embedded into the muscle.

I would recommend checking out some of the learnings from the keto diet. You may or may not subscribe to it, but they had to very carefully tread these lines when the body was essentially in starvation mode. A few things I know of:

1. You have to maintain a certain amount of protein intake (~10% to ~20%) to prevent your body burning lean muscle mass.

2. Too much protein gets converted into sugars, these in turn are easily stored as fats.

3. Maintain exercise, use it or lose it.

4. Don't over-exercise. "Exercise flu" results in limited performance and muscle loss through gluconeogenesis. You break down muscle and convert it to energy due to lack of carbohydrates.

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

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!

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

I'm a fan of open bodybuilding, so I've been following the Ozempic usage trend for a while now. Given the findings on this study, I can see how it may become an essential drug on bodybuilders stacks.

Hunger reduction + supraphysiological muscle gain from steroids and growth hormone - (heart) muscle reduction = win/win?

Heart problems are one (of many) of the main problems these guys face, so I won't be surprised if Ozempic is used to kind of "balance" the effects of other drugs.

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

Keyword: "in mice"

Second gotcha: how much of the decrease is just attributed to the lower mass of the subject after the weigh-loss treatment

Though it's one good reminder that "catabolism" and "anabolism" are less selective than we wished to

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.

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.

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?

>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.

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.

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

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

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

These comments make me very sad about scientific literacy. 342 comments and 'control' appears 12 times (before this comment).

Without proper control you could also say that weight loss is associated with loss of heart muscle mass.

Ozempic can use their cash to start an exoskeleton division.

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.

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.

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.

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."

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

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.

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

It would seem wise to potentially add a low dosed anabolic androgenic steroid like Anavar (Oxandrolone) [1] during a course of Ozempic. This would help keep skeletal muscle in tact during a calorie deficient period. A low dose wouldn't be expected to cause much, if any, side effects. But it's something that would be best put through rigorous studies.

But bodybuilders have been using tricks like these for decades (obviously at much more ridiculously high amounts) that work quite successfully for this exact purpose.

[1] https://en.wikipedia.org/wiki/Oxandrolone

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

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

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

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

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

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?

Don’t care. I’m down 30lbs.

There are no free lunches in nature.

which weight loss drug?

The marketing is astounding.

"Weight-loss drug."

Oh, would that be Semaglutide?

<click>

Hey, would you look at that!