We’re nearing the utopic phase for this drug (if we aren’t already there)
Mindful that this also lowers muscle mass (can weight train and eat enough protein to compensate slightly)
AND less easily mitigated lowers bone mass, weakens tendons, and weakens ligaments.
It’s a great option if the patient is diabetic and their current lifestyle/condition has worse outcomes than the side effects listed, but we’re hearing from celebrities like this is a vitamin D pill
IIUC, it depends how the patient would lose that weight. Afaict, these drugs work by lowering appetite overall and making people poop out lots of food before it's fully digested. If the patient macros are still bad, the same proportions as before the drug, they'll have deficiencies such as protein, fiber, electrolytes, vitamins (esp fat-soluble ones), etc. But hopefully it's just for short term. (star)
So to get back to your question, one could lose the weight in the best possible way by correcting their diet, eating less, doing HIIT, fasting, good supplements like creatine, stress reduction through breath work and meditation, and resistance training and end up in a very strong position.
Please anyone correct me on this.
(star) Anecdote about my friend: He went on Metformin for a few years, had lots of diarrhea, and lost about 30 pounds and is skinnier than me. At this point, he could really really get into a strong health position having had that shortcut. His eating habits even got a little better from wearing a glucose monitor. He's sick of the diarrhea which really keeps him from wanting to be out of the house for long, and is slowly looking for some intriguing physical activities. So I think these drugs can help people.
It only lowers muscle mass and bone density because your body only secretes the bare minimum amount of insulin needed to maintain while on it. Put another way, you want insulin sensitivity when you cut, but you want insulin resistance when you bulk. If you know what you're doing it can greatly increase your strength and lean body mass. I took compounded semaglutide for one week, cut about 15 lbs, then bulked 45+ lbs over the next few months.
Obesity has a whole galaxy of side effects an absurdly strong correlation with a large increase in all-cause mortality. From a cost-benefit standpoint, ozempic would be an obvious win even if the side effects were much worse than they actually are.
> We’re nearing the utopic phase for this drug (if we aren’t already there)
GLP-1 increasingly looks like a vitamin.
It is "essential to [humans] in small quantities for proper metabolic function" [1]. But what our body produces gets eliminated in minutes [2]. Not everyone needs supplementation and too much can be harmful. But a deficit results in ultimately-fatal chronic conditions.
> Mindful that this also lowers muscle mass (can weight train and eat enough protein to compensate slightly)
AND less easily mitigated lowers bone mass, weakens tendons, and weakens ligaments.
These are the common effects of weight-loss and they and other risks are why you should be under the care of a specialist in obesity and/or diabetes, a nutritionist, and a trainer.
Yeah, I'm with you. It seems like there are some almost miraculous results from this class of drugs, but I'm very concerned what's going to rear it's head 5, 10, 15 years down the line
I don't envy anyone tasked with calculating the risk/reward benefit of this drug versus obesity and friends.
These drugs aren't a free lunch and from my understanding can't be stopped without dramatic lifestyle changes or most of the weight comes right back. 20+ years of losing bone density and connective tissue mass is going to be catastrophic in old age for people who have to stay on it long term but really so is the obesity, diabetes, and heart disease. It's a tough moral quandary.
It seems like the most corrupt time with the government almost entirely asleep at the regulatory switch. Perhaps that's just a coincidence that so many "miraculous" results seem to exist.
Tangentially, I wonder how people mentally model "too-good-to-be-true"?
"Everything is a tradeoff" is almost a core belief for me, but in the same time, in technology, the "too-good-to-be-true" events does turn out to be real every once a while (I'm using technology here as a general concept).
I do understand GLP-1 does have some downsides, like cost, or in my own experience, nausea. But the tradeoff seems negligible compare to the upside. Part of me feels like that there is some hidden trade-off somewhere that we're not discovering, but part of me also wonders if it's a once in while technology jump, where it is just better.
Anyway, I guess I'm just a bit wary to throw away the "everything is a tradeoff" mental model that has worked quite well for me.
Antibiotic tradeoffs are enormous. They can completely and permanently ruin your microbiome.
Giving them to children has been linked to many conditions such as obesity, allergies, and asthma [0]. They have saved countless lives from infections but their use and overuse has undoubtedly contributed to significant and widespread health problems.
That’s a bit of a straw man. While the benefits of antibiotics are certainly untold millions of lives saved, we’re only now understanding their long term impacts on our gut biome. Let alone their overuse in factory farms.
There are considerable numbers of people who have severe complications with antibiotics, and their overuse over time has left us in a position where the functional pools of antibiotics keeps getting smaller and smaller and the pool of superbugs gets more and more virulent.
Who knows the long term ramifications of this new class of weight loss drugs. This smells to me like the Prozac craze in the 90s when everyone was on it or giving it to their kids. Or the olestra boom until everyone was literally crapping their pants.
Or tangentially, the over proscribing of novel opioids. Look what that has wrought in our society.
Could this new class of drugs be helpful, absolutely. Do we know the long term issues, nope. I think there are people who can use this therapeutically and there are others who use it as a quick fix because they have no self control. In a lot of ways it also feels a little ironic to look at fiction like the food indulgent scenes of “Hunger Games” and South Park and see that happening for real.
> "Everything is a tradeoff" is almost a core belief for me, but in the same time, in technology, the "too-good-to-be-true" events does turn out to be real every once a while (I'm using technology here as a general concept).
Every once in a while? Our lives are better in so many tangible ways than they were even 100, 200 years ago.
Just for a start - instead of 50% of children dying before the age of 5, we're down to tiny fractions of a percentage.
But sometimes things we're trading off are less relevant and so the equilibrium changes e.g. losing weigh is hard, because humans evolved in low-calorie environment and being able to stock fat was important.
The biggest problem with semaglutide is once you stop taking it things like blood sugar and body weight start to go back to where they were before. On average people gain back 70% of the weight they lost on the drug within the first year when they stop taking it. It seems likely this is going to be true with other addictions as well such as alcohol. While the effects are impressive, without addressing the underlying causes such as psychological factors that cause people to overeat or abuse other substances like alcohol it seems like we are just replacing one form of chemical dependance with another, albeit a healthier one.
While this is oft repeated, it’s not very relevant. First of all, some weight is kept off, which is a huge win. Secondly, the drug can be taken again. Thirdly, it will be a second chance for millions at a heather lifestyle. Once you get so fat, it becomes a doom spiral of low physical activity and low body image. Personal willpower and choice can have a huge impact but its very hard to start exercising when you can barely walk down the street.
It's not just that the weight is gained back but the rate that it's gained back. Imagine someone loosing 100 pounds on semaglutide and then gaining 70 pounds of it back in 1 year when they stop taking it. That's over 1 pound a week of weight gain, likely much faster than that individual gained the 100 pounds originally. That type of rapid weight gain is associated with even worse health effects than carrying the extra 100 pounds probably was, and that's just at 1 year, where will this individual be in 2 years, 3 years etc? Will they really keep that other 30% weight off? We don't have the data yet, but it doesn't seem likely they will. I'm not saying we shouldn't use these drugs, just that we need to understand that they are only the first step to a much longer strategy to improved health.
> it seems likely this is going to be true with other addictions as well such as alcohol
Why? We need to eat. We don't need to drink.
Removing alcohol for a year or more could allow both the body and environment to be adapted to a point where it is no longer presented in the same way.
Agreed, speaking from experience taking a long break from alcohol does wonders to reset the brain’s idea of what’s “normal” plus the simple act of just disrupting an engrained habit.
Won’t be the case for everyone but I think even taking it for a limited amount of time could do a lot for a certain type of excessive drinker.
i’m not sure whether there’s any physiological basis for this, but subjectively having an addiction feels a lot like having an additional need in the same vein as hunger and thirst. The addict’s mind is convinced it does “need” the substance.
How is this any different than treatments for high blood pressure and other chronic illnesses? I hear this refrain often, which diminishes the incredible achievement and benefit of these new drugs.
I think there are two kinds of people, those for whom taking medications for the rest of their lives is unthinkable, and those for whom it's completely normal. I'm definitely in the latter camp but the cultures colliding can be a real surprise.
Just... keep taking it then? What's the downside of taking a drug that has a number of beneficial effects, especially the reduction of addictions (food, alcohol) that have high fatality rates?
Well then maybe we shouldn't use it unless the consequences are severe enough to warrant them. In particular we shouldn't use them without trying behavior modification first.
I'm an interested bystander to this obesity drug mania currently happening but I'm curious as to whether the folks taking this for obesity or being overweight have to take it for the rest of their lives?
I.e. if an obese person gets skinny with Ozempic and then stops taking it, can they keep the weight off?
If not, it seems like the "perfect" money-making drug, i.e. it doesn't cure anything permanently, its expensive, and patients have to take it until they die.
Now sure, it's obviously better than being obese and unhealthy, but does it bother anyone else (in a philosophical kind of way), that we are treating the symptoms and not the causes here? We're teaching people that everything can be solved by popping more pills and not treating the psychological issues that result in so much obesity. It also doesn't result in anyone learning any good lesson, e.g. that working gets results. In this case the lesson is, my bad decisions or mental health don't matter, I can just pop pills for all my problems...
They can keep it off if they keep eating like they’re on it.
Most can’t do that or they wouldn’t have needed it in the first place.
My understanding is that many do well on a much-reduced dose once reaching their desired weight, or simply stop the drug but then return to it for a couple months if they backslide.
[edit] nb a fair number can do pretty well without it, though, as they find it easier to stay motivated to maintain a good weight than to overcome the intertia and slooooow results of losing weight from an already-very-unhealthy weight. Doesn’t hurt that working out is a hell of a lot easier and more enjoyable when you’re already a healthy weight. Seems those who’ve in the past successfully put in effort to hold a healthy weight for a good amount of time but then eventually gained a bunch, have an easier time keeping their healthier weight for quite a while once off the drugs.
It seems to depend on the person. If they use it like a 'miracle drug' then they'll tend to have relapse on cessation. If they use it as an opportunity to build new, healthy habits they have a better chance. No doubt underlying biology plays a role too, after all some people are overweight because they found themselves in a rut, and other are overweight because they're constantly hungry. Those latter people tend to relapse.
I'm also be interested in how this can affect a change of gut biome. Ie if a biome is partly responsible for diet cravings, would something like this help you restart your biome and put you in a better position to maintain?
> Now sure, it's obviously better than being obese and unhealthy, but does it bother anyone else (in a philosophical kind of way), that we are treating the symptoms and not the causes here?
I agree with everything you said, but what is the cause of obesity? It's convenience, abundance, corporations, and being sedentary. All of which are where most societies continue to move toward.
Have you tried exercising when you're fat? I've gained 20 lbs in the past year and, while I used to love playing tennis twice a week, now even walking is a chore.
This thread is full of people that think that fat people are only fat because it didn't occur to them to be thin.
Very exciting, we're going to see some serious "at scale" behavioral changes (obesity decline, addiction decline, possibly even social media usage decline) as soon as the cost of GLP-1 agonists gets driven down and manufacturing scales up.
I wonder which will happen first: discovery of effective small-molecule drugs in this class, or improvements of peptide manufacturing to the point that cheap generics become possible. There are only 7 years left on the semaglutide patent but its manufacturing is currently so complicated that I don't expect really cheap generics after patent expiration.
I am not familiar with the specifics of manufacturing these drugs, but peptide molecules have been synthesized for decades. What makes these special?
Considering the high prices of the marketed product, I would dispute the idea that generic manufacturers will not leap at the chance to get a taste. Even if it is technically complex, they have years to perfect a recipe, get it GMP qualified, and on shelves the day patents expire.
My understanding is that the manufacturing costs have nothing whatsoever to do with why they’re so expensive. It’s already damn near aspirin-cheap to make.
Unfortunately, the story for people who discontinue the drug is less rosey. Many regain some or all of the weight lost; it appears to be a temporary alternative to stomach surgery.
Does this happen any more often than when people lose weight by other means? I was under the impression that something like 90-95% of people who lose significant weight gain a lot of it back.
A study says these drugs could prevent 1.5 million cardiac events over 10 years, add in a reduction in alcoholism and the governments should be giving away these drugs to save on healthcare costs...
----- We identified 3999 US adults weighted to an estimated population size of 93.0 million [M] (38% of US adults) who fit STEP 1 eligibility criteria. Applying STEP 1 treatment effects on weight loss resulted in an estimated 69.1% (64.3 M) and 50.5% (47.0 M) showing ≥ 10% and ≥ 15% weight reductions, respectively, translating to a 46.1% (43.0 M) reduction in obesity (BMI ≥ 30 kg/m2) prevalence. Among those without CVD, estimated 10-year CVD risks were 10.15% “before” and 8.34% “after” semaglutide “treatment” reflecting a 1.81% absolute (and 17.8% relative) risk reduction translating to 1.50 million preventable CVD events over 10 years.
Except it's not meant as a drug you take for life, as it will require higher and higher dosages in order to get the body to respond.
The problem isn't the results, the problem is the factors that caused the obesity. I'm for it as long as it comes with healthy lifestyle changes as that's the only true way to have a long-term impact.
The effects of GLP-1 drugs are fascinating and I am curious whether we will see approvals beyond the current diabetic and weight-loss applications.
In just the last months stories of increased fertility [0] and reduction of heart attack risk [1] popped up, but more data is definitely needed to fully asses the effects.
Anyone read David Brin's story "The Giving Plague."?
These drugs have the flavor of that. I'd be reluctant to take them not because the Thyroid cancer risk or loss of muscle mass. Or the possibility that if I stopped I might gain more weight then when I started.
I'd be reluctant because in it's weird hormonal backdoor way it seems to be really messing with your personality. I'm not convinced the grass is actually greener on the other side - I tend to be of the belief that it's no better or worse; it's just a different set of tradeoffs.
All that said while I'm not skinny I'm also not (in my and I assume my dr's judgement) a candidate for this drug. Maybe if I was I'd feel differently.
Readit News
Mindful that this also lowers muscle mass (can weight train and eat enough protein to compensate slightly)
AND less easily mitigated lowers bone mass, weakens tendons, and weakens ligaments.
It’s a great option if the patient is diabetic and their current lifestyle/condition has worse outcomes than the side effects listed, but we’re hearing from celebrities like this is a vitamin D pill
> AND less easily mitigated lowers bone mass, weakens tendons, and weakens ligaments.
Does it do these things any more than losing the same amount of weight by other means in a similar time frame?
"Diet-induced weight loss reduces muscle mass without adversely affecting muscle strength" [1]. (Not sure about magnitudes.)
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764193/
So to get back to your question, one could lose the weight in the best possible way by correcting their diet, eating less, doing HIIT, fasting, good supplements like creatine, stress reduction through breath work and meditation, and resistance training and end up in a very strong position.
Please anyone correct me on this.
(star) Anecdote about my friend: He went on Metformin for a few years, had lots of diarrhea, and lost about 30 pounds and is skinnier than me. At this point, he could really really get into a strong health position having had that shortcut. His eating habits even got a little better from wearing a glucose monitor. He's sick of the diarrhea which really keeps him from wanting to be out of the house for long, and is slowly looking for some intriguing physical activities. So I think these drugs can help people.
GLP-1 increasingly looks like a vitamin.
It is "essential to [humans] in small quantities for proper metabolic function" [1]. But what our body produces gets eliminated in minutes [2]. Not everyone needs supplementation and too much can be harmful. But a deficit results in ultimately-fatal chronic conditions.
[1] https://en.wikipedia.org/wiki/Vitamin
[2] https://en.wikipedia.org/wiki/Glucagon-like_peptide-1
These are the common effects of weight-loss and they and other risks are why you should be under the care of a specialist in obesity and/or diabetes, a nutritionist, and a trainer.
All the results are from lowering BMI, being fat is just this unhealthy.
These drugs aren't a free lunch and from my understanding can't be stopped without dramatic lifestyle changes or most of the weight comes right back. 20+ years of losing bone density and connective tissue mass is going to be catastrophic in old age for people who have to stay on it long term but really so is the obesity, diabetes, and heart disease. It's a tough moral quandary.
Losing weight means losing the muscle “scaffolding” also.
Until I see proof that these drugs result in dramatically more muscle mass loss, I’m going to assume the argument is FUD.
Dead Comment
"Everything is a tradeoff" is almost a core belief for me, but in the same time, in technology, the "too-good-to-be-true" events does turn out to be real every once a while (I'm using technology here as a general concept).
I do understand GLP-1 does have some downsides, like cost, or in my own experience, nausea. But the tradeoff seems negligible compare to the upside. Part of me feels like that there is some hidden trade-off somewhere that we're not discovering, but part of me also wonders if it's a once in while technology jump, where it is just better.
Anyway, I guess I'm just a bit wary to throw away the "everything is a tradeoff" mental model that has worked quite well for me.
Giving them to children has been linked to many conditions such as obesity, allergies, and asthma [0]. They have saved countless lives from infections but their use and overuse has undoubtedly contributed to significant and widespread health problems.
0: https://academic.oup.com/femsre/article/42/4/489/5045017
There are considerable numbers of people who have severe complications with antibiotics, and their overuse over time has left us in a position where the functional pools of antibiotics keeps getting smaller and smaller and the pool of superbugs gets more and more virulent.
Who knows the long term ramifications of this new class of weight loss drugs. This smells to me like the Prozac craze in the 90s when everyone was on it or giving it to their kids. Or the olestra boom until everyone was literally crapping their pants.
Or tangentially, the over proscribing of novel opioids. Look what that has wrought in our society.
Could this new class of drugs be helpful, absolutely. Do we know the long term issues, nope. I think there are people who can use this therapeutically and there are others who use it as a quick fix because they have no self control. In a lot of ways it also feels a little ironic to look at fiction like the food indulgent scenes of “Hunger Games” and South Park and see that happening for real.
Every once in a while? Our lives are better in so many tangible ways than they were even 100, 200 years ago.
Just for a start - instead of 50% of children dying before the age of 5, we're down to tiny fractions of a percentage.
But sometimes things we're trading off are less relevant and so the equilibrium changes e.g. losing weigh is hard, because humans evolved in low-calorie environment and being able to stock fat was important.
https://www.healthline.com/health/semaglutide-withdrawal-sym...
Why? We need to eat. We don't need to drink.
Removing alcohol for a year or more could allow both the body and environment to be adapted to a point where it is no longer presented in the same way.
Won’t be the case for everyone but I think even taking it for a limited amount of time could do a lot for a certain type of excessive drinker.
I.e. if an obese person gets skinny with Ozempic and then stops taking it, can they keep the weight off?
If not, it seems like the "perfect" money-making drug, i.e. it doesn't cure anything permanently, its expensive, and patients have to take it until they die.
Now sure, it's obviously better than being obese and unhealthy, but does it bother anyone else (in a philosophical kind of way), that we are treating the symptoms and not the causes here? We're teaching people that everything can be solved by popping more pills and not treating the psychological issues that result in so much obesity. It also doesn't result in anyone learning any good lesson, e.g. that working gets results. In this case the lesson is, my bad decisions or mental health don't matter, I can just pop pills for all my problems...
Most can’t do that or they wouldn’t have needed it in the first place.
My understanding is that many do well on a much-reduced dose once reaching their desired weight, or simply stop the drug but then return to it for a couple months if they backslide.
[edit] nb a fair number can do pretty well without it, though, as they find it easier to stay motivated to maintain a good weight than to overcome the intertia and slooooow results of losing weight from an already-very-unhealthy weight. Doesn’t hurt that working out is a hell of a lot easier and more enjoyable when you’re already a healthy weight. Seems those who’ve in the past successfully put in effort to hold a healthy weight for a good amount of time but then eventually gained a bunch, have an easier time keeping their healthier weight for quite a while once off the drugs.
I agree with everything you said, but what is the cause of obesity? It's convenience, abundance, corporations, and being sedentary. All of which are where most societies continue to move toward.
Just take the slim pill and stay put, everything is going to be alright
This thread is full of people that think that fat people are only fat because it didn't occur to them to be thin.
Considering the high prices of the marketed product, I would dispute the idea that generic manufacturers will not leap at the chance to get a taste. Even if it is technically complex, they have years to perfect a recipe, get it GMP qualified, and on shelves the day patents expire.
In the interim, the drug helps those in need of intervention.
https://www.fractyl.com/fractyl-health-demonstrates-signific...
https://www.remain1study.com/remain-1-study/
----- We identified 3999 US adults weighted to an estimated population size of 93.0 million [M] (38% of US adults) who fit STEP 1 eligibility criteria. Applying STEP 1 treatment effects on weight loss resulted in an estimated 69.1% (64.3 M) and 50.5% (47.0 M) showing ≥ 10% and ≥ 15% weight reductions, respectively, translating to a 46.1% (43.0 M) reduction in obesity (BMI ≥ 30 kg/m2) prevalence. Among those without CVD, estimated 10-year CVD risks were 10.15% “before” and 8.34% “after” semaglutide “treatment” reflecting a 1.81% absolute (and 17.8% relative) risk reduction translating to 1.50 million preventable CVD events over 10 years.
https://news.ycombinator.com/item?id=37166206
The problem isn't the results, the problem is the factors that caused the obesity. I'm for it as long as it comes with healthy lifestyle changes as that's the only true way to have a long-term impact.
[0] https://www.independent.co.uk/life-style/pregnant-women-ozem...
[1] https://www.theguardian.com/science/article/2024/may/14/weig...
These drugs have the flavor of that. I'd be reluctant to take them not because the Thyroid cancer risk or loss of muscle mass. Or the possibility that if I stopped I might gain more weight then when I started.
I'd be reluctant because in it's weird hormonal backdoor way it seems to be really messing with your personality. I'm not convinced the grass is actually greener on the other side - I tend to be of the belief that it's no better or worse; it's just a different set of tradeoffs.
All that said while I'm not skinny I'm also not (in my and I assume my dr's judgement) a candidate for this drug. Maybe if I was I'd feel differently.