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

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.

My wife told me exactly this - potentially all muscle mass loss (and she made sure I understood that 'all' part), yoyo effect once stopping, potentially other nasty long term/permanent side effects, and overall just a bad idea, attacking the problem from a very wrong direction. Just look at musk for example - he pumps himself with it obsessively and the results even for richest of this world are... not much there (or maybe his OCD binging would make him 200kg otherwise so this is actually some success).

Then all the folks come who say how to helped them kickstart a positive change, like its something against those facts above. All the power to you, just don't ignore facts out there and don't let emotions steer your decisions. You only have 1 health and it doesn't recharge that much, and that short time we have on this pale blue dot is significantly more miserable and shorter with badly damaged health.

I’ve seen multiple friends go from eating like shit, including chugging sodas, to not compulsively ordering dessert and no sodas in the house. I think all of them have since quit Ozempic, each seeing some rebound but nothing comprehensive and, most notably to your argument, not in the behaviour modifications.

Just like in programming, there is no silver bullet; there's only hard work.

Skinny people move to the US and get fat. They're not skinnier back in their home country because they've got greater willpower or are harder workers, but because they aren't in the US. If harder work isn't why skinnier countries are skinnier, we shouldn't expect it to help us out of our problem, and indeed, we have nothing else we've studied that is terribly effective over time, and certainly nothing cheap enough to deploy on a large scale.

Again, yes, for an individual your perspective is the only thing one has (well... until these drugs) but looking from a policy level, it's useless.

The only really effective policy is to inform people that that is the simple, honest truth of every single person, and that the quality of food we eat is important in that equation.

Eat better food, be more active. Yes, it is difficult, especially for us peasants.

But that is science. I hope a miracle drug helps folks preyed upon by the food industry, but side effects of that industry's drugs leave me skeptical of their being lastingly beneficial.

It's literally not effective. As in, well-studied, isn't effective.

Again, it's the only guidance one has to go on, personally, so it's fine to hold onto that as an individual navigating the world, but it is emphatically not effective policy.

But sure, it's not effective but only because people have a hard time fending off our cravings. It requires breaking our cycles and learning how to eat better and eat less and do something other than lay around watching tv.

As to policy: if we curbed the corps' ability to profit off our ill-health, then we'd surely be doing something positive for society. It would also be very helpful to have cleaner air and more and larger parks that are safe for one and all. What can I say, I dream big.

Personally, I recommend everyone avoid any and all refined sugar and alcohol, as they mess with our hormones and gut biome. And that's very difficult for 2024 America, evidently.

No one is questioning CICO.

The part being questioned is why it's more difficult for others. For example, my wife and I share an almost identical diet and activity level, yet i struggle to keep weight on and she struggles to keep weight off and with similar lifestyles. CICO works of course, but not only do our bodies innately do different things with the calories that they process but we simply experience that world differently.

I could drop down to unhealthily thin levels without even trying. She would be in misery even trying to maintain my weight.

This isn't an excuse necessarily. Rather just saying there's a lot of information beyond simple CICO that we're missing. Complexity in biome, addictive behaviors, and a full on assault from the food industry.

The ease i have in weight loss is not due to my own efforts. Thin people shouldn't break their arm patting themselves on the back, because imo it's usually not due to our own will.

If you and your wife eat the same diet in the same quantities, it's no surprise she would have a propensity to gain weight and you wouldn't unless she's substanially larger (i.e., taller and/or heavier) than you. Women in general just burn fewer calories for similar sized vs. men. That said, this is ALL population averages. Everyone knows someone who seems to be able to eat literally anything and never gain weight... it likely is just as simple as their metabolism is such that they burn more calories than the average person. Population variation will always lead to some people with outliers both in high expenditure and low expenditure.

That's the point though. I'm saying that we burn calories at different rates. We burn fat at different rates. We have different rates of addiction, cravings, etc.

Just saying CICO is the same boring and borderline inaccurate language that has led to nearly zero change in the population at large. may as well just tell them to use physics correctly to lose the weight, because it's the same effective language.

To even determine CICO is fraught with difficulty and inaccuracy in both CI and CO. You can hand make everything, weigh every ingredient, and even then you struggle to determine how much you're CO. At best you'll have an estimated CO but then what do you do when your weight isn't changing? you have to start adjusting the math because clearly you're not burning as much as you think you are.

This is made much, much worse with the fact that we don't actually burn that many calories with exercise. And even with what is burned, the rate of burn changes drastically based on your current weight and how long you've been losing weight.

The fact is, the point is, CICO ignores all the real challenges and thereby all the real problems people need to understand and face.

I think we'll have to disagree here. At the end of the day CICO is the formula. That obviously doesn't account for the human factor in regards to the adherenace rate, but it does, fully encompass the 'if you were a robot and were fully adherent how do you lose/gain weight' method.

> To even determine CICO is fraught with difficulty and inaccuracy in both CI and CO. You can hand make everything, weigh every ingredient, and even then you struggle to determine how much you're CO. At best you'll have an estimated CO but then what do you do when your weight isn't changing? you have to start adjusting the math because clearly you're not burning as much as you think you are.

I won't say it's 'easy', but it's also not particularly hard either with the multitude of widely available food databases for measuring calories in. As for calories out, it's arguably even simpler: measure your weight every day, take the average across the week, and watch your weight trend week over week. Calories out can be calculated simply by comparing calories in vs. weight lost/gained... and extrapolating. It's simple math, and very effective in my experience.

> This is made much, much worse with the fact that we don't actually burn that many calories with exercise. And even with what is burned, the rate of burn changes drastically based on your current weight and how long you've been losing weight.

Essentially irrelevant if you follow my above suggestion for how to measure calories out. It's just part of the bucket of calories burned, so as long as you're reasonably consistent with the amount of exercise you do then your averaged weight will account for any exercise based caloric expenditure.

This is like trying to solve aerodynamics with Newtonian physics only. It’s not useful. CICO ignores the variability of base metabolism.

Metabolic syndrom is characterised by the basal metabolic rate reducing in response to reduced calorie intake or increased caloric expenditure. In most of us this is good. It gets the immune system to quit mucking around, for instance. In the obese, however, it can sometimes mean their bodies will literally stop doing essential shit before it will concede and begin burning fat. It will then do everything it can to refill those fat cells.

You can model a human thermodynamically. But to my knowledge, this isn't used in medicine because it isn't practical. (I'm saying this, by the way, as someone who can eat anything and laze around and not gain weight because my metabolism is tuned the other way.)

CICO reminds me of something we do in finance: burying the complexity in a magic variable. For CICO, it's the CO. Because if you decompose it into its active and inactive components. Exercise is the former. But the latter absolutely dominates that term.

I’m sure there’s some people that this might apply to, but I suspect it’s a much (much) smaller subset than people that are actually obese. For the rest, just decrease your intake until you lose weight. Not much else.

> You can model a human thermodynamically. But to my knowledge, this isn't used in medicine because it isn't practical. (I'm saying this, by the way, as someone who can eat anything and laze around and not gain weight because my metabolism is tuned the other way.)

Exactly what variables are missing then? We can agree that exercise, although certainly burns some calories, is not really the lever you want to pull if you actually want to lose weight by itself. What other variable besides changing how much food you eat would you suggest?

It's not a profound statement to say if you starve in a desert you'll lose weight. The question is how we can apply this to real, normal people. Or if it's even possible in a food-weaponized world.

My view is that we're in the realm of addiction more so than simply answering "how" they mechanically lose weight. This is a public health crisis, one we need to be open to exploring.

Should we do more research to find if anything anything specific that may be causing overeating or food non-satiety? Sure. Is the answer likely to be something that is essentially 'tastier food is easier to overeat, and tastier food is much more available than it used to be'? I suspect that is the likely conclusion.

I think GLP1 agonists are a great tool to be used to create that so-called 'willpower' to stop overeating (or, an easy way to reduce food noise, whatever you want to call it). The next step is figuring out how, as a society, we make it easier for folks to make that lifestyle change without a constant stream of 'willpower drugs' for the rest of their life.

Yes, and again - as i said previously. No one is questioning if CICO works. That's like if questioning if physics works. No one is doing that. The laws of the universe are still intact. Talking about humans is the constructive conversion most people are having.

Other people are, in fact, questioning CICO. Look at the other commenter talking about base metabolism changes.

To put an analogy to this: Gambling addicts often lose lots of money at casinos. The behaviors that lead to them being addicted to gambling are in many ways likely equivalent to overeating problems. Nobody asks 'why are gambling addicts losing money?' because we know the reason (casinos have the house edge... you always lose on aggregate). And yet, with food, people consistently ask the question 'why are people so obese?' as if the answer isn't very obvious: they're eating too much food. It's purely as simple as that. The behaviors that lead to eating too much aren't nearly as focused on, in my opinion. Much time is spent on 'the kinds of foods eaten' and how specific things are bad for you, which is essentially like arguing that people should play more blackjack and less roulette or something.