9 ms·

Studies show almost all subjects regained the weight and reversed gains within 2 years. This means underlying issues (e.g., food addiction) aren't being address

Studies show almost all subjects regained the weight and reversed gains within 2 years. This means underlying issues (e.g., food addiction) aren't being addressed. Short of changing habits, the only maintenance solution is lifelong drug use and that doesn't sit well with me.

PeterHolzwarth 3mo ago
A couple years of reduced weight, and all the benefits that entails, doesn't sound bad.
crooked-v 3mo ago
Plenty of people have lifelong drug use of, say, caffeine, or aspirin as a blood thinner, or various antihistamines. Why is this somehow worse? Particularly keeping in mind that it's very easy to make, so once the patents expire, it's going to be dirt cheap as generics everywhere.
- joshuamcginnis 3mo ago
  I'm just sharing my personal preference and not trying to tell people how to live their lives. I don't like personally like the idea that I'll only be healthy if I take this drug for the rest of my life when I could (again - speaking for me), be more disciplined about the food I put into my body.
  - kolinko 3mo ago
    “be more disciplined” - did you read any studies about the sources of obesity? Or do you struggle with weight since childhood yourself?
    - deleted 3mo ago
      [deleted]
  - m1keil 3mo ago
    Why this has to be all or nothing? You can use the drug to loose weight while trying to understand the underlying problem.
  - deleted 3mo ago
    [deleted]
  - thaw13579 3mo ago
    People have a variety of intensities of cravings and capacities for self-regulation (with a magnitude that is largely out of their control). Discipline only works for people where the capacity for self-regulation outweighs the intensity of cravings. These cravings are huge though because our food system is engineered to be both extremely calorie rich and appealing. It's hard to blame people when they're surrounded by fast food restaurants on every corner that has been engineering to target what's called the "bliss point" when experiencing their food. Looking at this a different way, maybe the discipline / self-regulation needs to be applied at the societal (not individual) level, to improve the environment in which we all live?
wpm 3mo ago
Why not? People take depression meds, blood pressure meds, all kinds of meds for their whole life. I'll be on omeprazole for reflux my whole life. It doesn't solve the underlying problem of my gut being prone to overpumping acid into my stomach. So omeprazole is problematic? The underlying issue is being treated, it's treated by taking the drug. It works. It's doing its job. I'd be curious as to how you came to this conclusion.
- joshuamcginnis 3mo ago
  I think there's a distinct difference between taking medicine for things you can fix on your own (diet + exercise) vs things you cannot (excess acid production).
  - ceejayoz 3mo ago
    > things you can fix on your own (diet + exercise) We have decades of research showing this is more in the "excess acid production" realm of things.
    - applfanboysbgon 3mo ago
      We also know there's a replication crisis in psychology and medicine, that it's easy to publish results that show the effect you're looking for, that there are rich, developed countries with obesity rates <5%, and that the obesity rate for Western countries spiked in recent years. This idea that Americans are genetically pre-ordained to be fat seems like fanciful thinking.
      - ceejayoz 3mo ago
        > We also know there's a replication crisis in psychology and medicine… It seems unlikely to extend to bariatric surgery outcomes. > This idea that Americans are genetically pre-ordained to be fat seems like fanciful thinking. This idea that Americans are genetically pre-ordained to lack willpower seems like fanciful thinking.
anon291 3mo ago
Why? If you have too much help or whatever being produced such that your body eats too much, just take a drug. The harm of being fat is worse than anything ozempic does
vidarh 3mo ago
Given that we know that diets and changing habits doesn't have lasting effects, what doesn't sit well with me is to risk my health to avoid taking a drug that helps.
- brazukadev 3mo ago
  changing habits do have lasting effects, I'm not part of this "we" that doesn't know that.
  - topgrain2 3mo ago
    People talk past each other on this because for an individual it technically can work, and sometimes does, but on a population level, as extensively studied by people whose job it is to study that, it definitely does not work. Even with tons of regular attention from professionals and a cohort selected to have above-average motivation, it’s surprisingly poorly-performing (and that’s a crazy expensive level of intervention) Think about how we describe contraceptives, medically speaking: a failure rate is tracked and promoted that’s the in the wild rate of failure, not the ideal-use rate of failure (which can be effectively zero!). The diet and exercise equivalent of a contraceptive couldn’t be sold, because its failure rate would be way higher than its success rate. So “we” (people who’ve paid attention to the science on it) know it doesn’t work (on a population level), like for-sure definitely does not work, but a person reads this assertion of fact and goes “but wait it worked for me, this person must be dumb or something” but that’s not it. It’s two different perspectives on what it means for it to “work”.
    - yakz 3mo ago
      I think it'd be more accurate to say that informing people that they should change their behavior doesn't work. A person changing their behavior can escape obesity. The reality is that most people won't be able to change their behavior without some other kind of assistance.
      - topgrain2 3mo ago
gedy 3mo ago
The "underlying issues" are not all moral failings as you hint. In my case, as I've aged my appetite due blood sugar/insulin resistance/etc means I'm basically hungry all the time if I restrict calories to maintain lower body weight. Yes - even if I exercise frequently. Yes - even with healthy food and snacks. My wife tells me my stomach is growling at night. I will slowly gain about 10-15lbs a year due to excess calories if I try to maintain weight at < overweight BMI. GLP-1 drugs have been great to take that edge off.
3stacks 3mo ago
It’s the food equivalent of declaring bankruptcy. If you don’t fix the behaviours you’ll just end up in debt again.
- kolinko 3mo ago
  This assumes underlying behaviours are core reason. Research (tein, adoption) suggests otherwise
  - yakz 3mo ago
    Practically speaking, any person could starve themself (short of death) and lose weight. In almost all cases there is no magic to storing more energy than you need.
    - shadowpho 3mo ago
      Practically speaking any person cannot maintain that for significant length of time. Dieting has like a 99% fail rate by year 2. It’s hard to maintain that for many people — your body will keep you in starvation mode, keep you hungry and hang on to every calorie received.
LaurensBER 3mo ago
I've gained and lost 10kg twice in my life. Maintaining the weight loss isn't that hard once you've a rhythm dialed in. In my case I just weight myself daily, track the weight and scale my food consumption with the current trend. If I'm gaining weight I'll skip a meal. It takes a while to figure out what works for you but I can tell you that making small lifestyle changes to maintain your weight is fairly easy compared to figuring out how to lose 10 kg.
- kolinko 3mo ago
  Just because it wasn’t hard for you doesn’t mean it isn’t hard for the others. Grom what you said it seems you just had some bad habits you had to fix and that’s it.
- coffeemug 3mo ago
  When I was lifting weights I went from 170lbs to 210, and back to 170. Doing that isn’t technically hard, and maintaining is even easier. But I had to think about it _all_ the time. Maybe it’s because I’m older now, but I just don’t want to spend that much effort thinking about food.
  - faangguyindia 3mo ago
    lifting weight isn't efficient for weight loss. Without calorie deficit, you'll not lose much weight by lifting alone.
    - SoftTalker 3mo ago
      You'll probably gain weight in fact. Muscle is heavier than fat.
flextheruler 3mo ago
Unfortunately for a lot of people with weight issues it stems from becoming overweight during puberty which is uniquely bad. Your body's appetite signals are permanently impaired if you become overweight during puberty because during this window your fat cells don't just increase in size, but also in number and this increased quantity does not go away once created. Fat cell shrink as weight is loss, but they are not destroyed and they are responsible for appetite signaling. It's one of the reasons that childhood obesity is actually leagues worse than it first appears and I think should be considered child abuse in extreme circumstances.
- apt-apt-apt-apt 3mo ago
  What you said isn't unique to puberty, it's the same with being overweight in adulthood (AIUI).
SubiculumCode 3mo ago
And this morning, I cut another hole in my belt. Turns out, losing weight and being thin was never about willpower or laziness in the face of absolute food abundance. It was mostly about whether a person was born lucky enough to have a moderate appetite, or was born burdened by exaggerated appetite. The underlying issue is physiological food cravings, not some personal failing or lack of willpower, and GLP-1 absolutely addresses those "underlying issues". That it isn't some one and done pill is hardly a realistic expectation as that would require probably genetic and epigenetic reprogramming.
- nihonde 3mo ago
  The idea that appetites are assigned at birth is a bold claim. Is there evidence to support it?
  - 9x39 3mo ago
    Well, not assigned by the hospital or your parents, but being a DNA-based lifeform a genetic baseline is a safe assumption. Experiences vary after that: https://pmc.ncbi.nlm.nih.gov/articles/PMC3052625/ https://pmc.ncbi.nlm.nih.gov/articles/PMC3052625/
    - s1artibartfast 3mo ago
      I think there is much stronger evidence that it is metabolic damage from overconsumption in an earlier stage in life. Not unlike if you shatter your legs, your recovery may be long and incomplete.
  - SubiculumCode 3mo ago
    Genetics and epigenetic factors.
- tedmiston 3mo ago
  [dead]
aaron695 3mo ago
[dead]
fragmede 3mo ago
The drug stops working if you stop taking it? Shocking! Heart medication for hypertension also stops working if you don't take it. Sure there's a vast conspiracy by the pharmaceutical industry to hook us all on drugs because we can't learn to exercise, but that's hardly Ozempic's fault. Now if you were looking at brain surgery that zaps the reward center of the brain causing permanent changes so the patient was less addicted to food, but the patient kept needing to have brain surgery, then you'd have a point, but "drug stops working if you don't take it" is hardly the gotcha some make it out to be. Insulin also stops working for diabetics if they don't take it. That's kind of medication's whole deal. Now that we know obesity can be controlled via medication, and it'll cost $foo over the lifetime of the patient, the next step is to optimize. If there is a treatment involving ultrasonic brain surgery that costs less than $foo, the expectation is for the market to find that. Ultrasonic brain surgery is in its infancy, but it's already showing utility for Alzheimer's and addiction. The real question is if the pharma companies are going to be able to keep it from going mainstream because it's less profitable for them.
JumpCrisscross 3mo ago
> almost all subjects regained the weight and reversed gains within 2 years Source? I thought it was 2/3rds of the weight regained, which is still a substantial long-term loss.
- shlant 3mo ago
  supposedly that comes mostly from observational studies whereas RCT's seem to show that at some point full regain will probably happen (although can take 1-2 years). The Observational studies don't seem to control for people stopping GLP-1's but still trying other drugs/weight loss methods which is where the discrepancy from RCT's seems to be.
  - JumpCrisscross 3mo ago
    > supposedly that comes mostly from observational studies whereas RCT's seem to show that at some point full regain will probably happen Do you have one you’d recommend reading?
SOLAR_FIELDS 3mo ago
Statins are a well understood mechanism of action for controlling cholesterol. We generally understand that people with cholesterol problems leverage statin therapy to address those, and there is a well audited corpus of placebo controlled double blind trials that demonstrate the efficacy of the solution for statin therapy. If you discontinue the statins, you lose the benefit to some extent. How is this situation fundamentally different?
- tqi 3mo ago
  Agree, same can be said of exercise. I think people consciously or unconsciously consider being overweight a moral failing and so are quick to point out the flaws.
mukbangpervert 3mo ago
What facts do you have that make you certain that the underlying issue is "food addiction" rather than, say, a difference in body chemistry that changes perceived hunger levels?
PaulHoule 3mo ago
It's not like anything else in terms of drugs, surgery, or lifestyle changes has been proven safe and effective. A person who is dependent on opiates or caffeine or cannabis can possibly live without those substances, you can't go "cold turkey" from food. Funny I just shot myself with a Zepbound autoinjector for the first time! My primary care doc told me he thought I was a good candidate a year ago but that he had trouble getting insurance to pay for it, it took me a year to get in with a specialist, insurance approved it right away, and now I am supposed to keep a food an exercise log. I am well in the obese BMI range but I've been active my whole life (e.g. I can't see how people can get through the day without going to the gym or something) so I have a high lean mass and don't look that fat with my clothes on. I've struggled for years with various conditions associated with "metabolic syndrome" and I'm on numerous maintenance medications already and may be able to delete some of them. I am currently around 250 lbs which has been my usual for the past 20 years or so. Had some luck with Zone, ketogentic and bean plan diets but couldn't stay on any of them indefinitely. Got my weight down to about 208 lb in six months when I quit taking antidepressants at my doctor's suggestion (never went back), had something like a manic episode where I manifested an "evil twin" who was vain highly motivated [1] and worked out like... a maniac and I also discovered I had TMJ dysfunction and took load off my jaw by throwing comically random food (cashews, seaweed, celery, potatoes, carrots, pork, ...) into a pot and grinding it with an immersion blended. Not sustainable, not least because my evil twin's antics got me kicked out of the gym. [1] as-a-fox one axiom is that "I never push on a string" and have a hierarchy of goals, non-goal goals and non-goals; my non-goal goals are his OKRs
dmayle 3mo ago
The issue isn't food addiction, it's a broken hunger response (broken by Howard Moskowitz intentionally in the name of profits)... You have to change your food regimen completely (higher fiber, more protein, less sugar, less carbs, less fat), and that's tough to do when you're surrounded by options that aren't... I think the real problem is that the symptom we're trying to treat is "overweight", and it's actually a two-stage problem... Fix the hunger response... and only then work on fixing the weight... Fixinig the latter without fixing the former means you'll always gain the weight back, fixing the former doesn't guarantee you lose weight (and is only temporary, if you're using drugs for it)... You have to go after both problems.
- basch 3mo ago
  We shouldn’t ignore grocery stores and marketing. Aisles and aisles of sugar drinks and colorful sugar packaging. The way society leaves it up to people to make their own decisions creates the problem at scale. Society essentially has to take weekly injections to avoid the temptation of coca cola.
- mynameisash 3mo ago
  What breaks the hunger response, and how does one fix it? Maybe it's well-known, but I read the starvation response Wikipedia page[0] and didn't grok it. [0] https://en.wikipedia.org/wiki/Starvation_response https://en.wikipedia.org/wiki/Starvation_response
  - SoftTalker 3mo ago
    Buy unprocessed food and prepare it yourself. Don't add sugar. Eating processed food and even most restaurant food is eating food that's designed to make you want more, not satiate you.
    - mynameisash 3mo ago
      I guess I should have asked about the technical mechanism of what causes and what actually 'breaks', and then what the technical remedy is.
rfv6723 3mo ago
The only underlying issue is an evolutionary mismatch: human evolution is too slow to keep pace with the modern abundance of food. What we now call food addiction is exactly what kept our ancestors alive during famines.
epihelix 3mo ago
If your biology is working against you, why not fix your biology? I'm not someone who needs to take GLP-1 receptor agonists, but if I had any issues with weight then I'd have no issue taking them life-long. The long-term health benefits are already strong enough to make it a no-brainer. If you are overweight and a GLP-1 drug helps you lose that weight, you will very likely live a longer, healthier and happier life by taking the drug. All that said -- this article was discussing a new paper in Cell Host & Microbe (high-impact Cell Press stable journal), https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(26)00179-4 https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(2... . And the point of that paper is that, at least in mice, the anti-depressive effect of GLP-1 receptor agonists was related to a change in gut microbiota, and not to activation of the GPL-1 receptor. It's work in mice only, so whether or not this holds in humans is unclear, but the researchers showed this worked in mice lacking the GLP-1 receptor and via fecal microbiota transplantation of bacteria from the guts of mice taking GLP-1s. So, if all you cared about were the mental health benefits of taking GLP-1s, then potentially you could gain these by simply changing your gut flora, without taking a GLP-1 drug at all. That might sit much better with you, by the sounds of it.
- port11 3mo ago
  If the food abundantly available is full of unhealthy ingredients and nutrient combinations meant to make you addicted, why not fix that? We blame biology and people’s willpower a lot, instead of considering how plenty of other or previous societies don’t/didn’t have this issue.
  - tqi 3mo ago
    The former isnt something an individual can change on their own
mullingitover 3mo ago
Diet programs as a weight loss strategy are utter failures, and it’s malpractice to push them as a treatment. Yet there are still people pushing them as something that’s perfect, if only you didn’t screw them up. When a treatment can’t fail and can only be failed, it’s big red flag for me.
thaw13579 3mo ago
The issue is that our modern world has engineered our food to be highly energy-dense and incredibly appealing, so the root cause is an evolutionary mismatch with our environment, which has diverged incredibly from early humans. Personally, I look at GLP-1 agonists as akin to wearing glasses. Some people are just born without the ability to regulate their appetite in accordance with our society, but there is a tool / prosthetic to change that, often that's a lifelong solution.
sakopov 3mo ago
Does loss of muscle mass, commonly associated with Ozempic weight loss, become an issue after regaining the weight? Can it result in proportionally more fat at the same body weight as before if exercise wasn't part of the regiment?
- theshrike79 3mo ago
  _All_ weight loss results in loss of muscle mass unless you do something about it. If you ingest less calories, you lose both muscle and fat mass.
- amanaplanacanal 3mo ago
  I believe loss of muscle mass is commonly associated with other weight loss methods too. It's not just ozempic. You need protein and exercise no matter how you are losing weight.
teliosix 3mo ago
Totally agree. My father is 75 and started taking GLP1. He stopped drinking immediately, lost 25lbs already and I can't imagine hasn't already added some time to his life. The calculus at 75 is much different than at 35 in terms of what "for life" means. It seems like there could be an issue too that it just stops working that well 10 years down the road. Not an issue for my father at 85 the way it would be for someone at 45.
whazor 3mo ago
What were the numbers again? Because I remember a significant amount of people actually did not regain weight. Although the majority did.
amunozo 3mo ago
But it does sit well with pharma companies.
theshrike79 3mo ago
Blood pressure and high cholesterol can both be genetic. So people just are on meds for both all their life. It doesn't cure anything - it's not supposed to.
QuantumGood 3mo ago
The "here's where you're getting it wrong" discussions on glucagon‑like peptide‑1 receptor agonists are paralleling AI discussons. Interesting to watch these two domains of knowledge sparking (mis)framing arguments happening at roughly the same time.

PeterHolzwarth 3mo ago

A couple years of reduced weight, and all the benefits that entails, doesn't sound bad.

crooked-v 3mo ago

Plenty of people have lifelong drug use of, say, caffeine, or aspirin as a blood thinner, or various antihistamines. Why is this somehow worse? Particularly keeping in mind that it's very easy to make, so once the patents expire, it's going to be dirt cheap as generics everywhere.

joshuamcginnis 3mo ago
I'm just sharing my personal preference and not trying to tell people how to live their lives. I don't like personally like the idea that I'll only be healthy if I take this drug for the rest of my life when I could (again - speaking for me), be more disciplined about the food I put into my body.
- kolinko 3mo ago
  “be more disciplined” - did you read any studies about the sources of obesity? Or do you struggle with weight since childhood yourself?
  - deleted 3mo ago
    [deleted]
- m1keil 3mo ago
  Why this has to be all or nothing? You can use the drug to loose weight while trying to understand the underlying problem.
- deleted 3mo ago
  [deleted]
- thaw13579 3mo ago
  People have a variety of intensities of cravings and capacities for self-regulation (with a magnitude that is largely out of their control). Discipline only works for people where the capacity for self-regulation outweighs the intensity of cravings. These cravings are huge though because our food system is engineered to be both extremely calorie rich and appealing. It's hard to blame people when they're surrounded by fast food restaurants on every corner that has been engineering to target what's called the "bliss point" when experiencing their food. Looking at this a different way, maybe the discipline / self-regulation needs to be applied at the societal (not individual) level, to improve the environment in which we all live?

wpm 3mo ago

Why not? People take depression meds, blood pressure meds, all kinds of meds for their whole life. I'll be on omeprazole for reflux my whole life. It doesn't solve the underlying problem of my gut being prone to overpumping acid into my stomach. So omeprazole is problematic? The underlying issue is being treated, it's treated by taking the drug. It works. It's doing its job. I'd be curious as to how you came to this conclusion.

joshuamcginnis 3mo ago
I think there's a distinct difference between taking medicine for things you can fix on your own (diet + exercise) vs things you cannot (excess acid production).
- ceejayoz 3mo ago
  > things you can fix on your own (diet + exercise) We have decades of research showing this is more in the "excess acid production" realm of things.
  - applfanboysbgon 3mo ago
    We also know there's a replication crisis in psychology and medicine, that it's easy to publish results that show the effect you're looking for, that there are rich, developed countries with obesity rates <5%, and that the obesity rate for Western countries spiked in recent years. This idea that Americans are genetically pre-ordained to be fat seems like fanciful thinking.
    - ceejayoz 3mo ago
      > We also know there's a replication crisis in psychology and medicine… It seems unlikely to extend to bariatric surgery outcomes. > This idea that Americans are genetically pre-ordained to be fat seems like fanciful thinking. This idea that Americans are genetically pre-ordained to lack willpower seems like fanciful thinking.

anon291 3mo ago

Why? If you have too much help or whatever being produced such that your body eats too much, just take a drug. The harm of being fat is worse than anything ozempic does

vidarh 3mo ago

Given that we know that diets and changing habits doesn't have lasting effects, what doesn't sit well with me is to risk my health to avoid taking a drug that helps.

brazukadev 3mo ago
changing habits do have lasting effects, I'm not part of this "we" that doesn't know that.
- topgrain2 3mo ago
  People talk past each other on this because for an individual it technically can work, and sometimes does, but on a population level, as extensively studied by people whose job it is to study that, it definitely does not work. Even with tons of regular attention from professionals and a cohort selected to have above-average motivation, it’s surprisingly poorly-performing (and that’s a crazy expensive level of intervention) Think about how we describe contraceptives, medically speaking: a failure rate is tracked and promoted that’s the in the wild rate of failure, not the ideal-use rate of failure (which can be effectively zero!). The diet and exercise equivalent of a contraceptive couldn’t be sold, because its failure rate would be way higher than its success rate. So “we” (people who’ve paid attention to the science on it) know it doesn’t work (on a population level), like for-sure definitely does not work, but a person reads this assertion of fact and goes “but wait it worked for me, this person must be dumb or something” but that’s not it. It’s two different perspectives on what it means for it to “work”.
  - yakz 3mo ago
    I think it'd be more accurate to say that informing people that they should change their behavior doesn't work. A person changing their behavior can escape obesity. The reality is that most people won't be able to change their behavior without some other kind of assistance.
    - topgrain2 3mo ago

gedy 3mo ago

The "underlying issues" are not all moral failings as you hint. In my case, as I've aged my appetite due blood sugar/insulin resistance/etc means I'm basically hungry all the time if I restrict calories to maintain lower body weight. Yes - even if I exercise frequently. Yes - even with healthy food and snacks. My wife tells me my stomach is growling at night. I will slowly gain about 10-15lbs a year due to excess calories if I try to maintain weight at < overweight BMI. GLP-1 drugs have been great to take that edge off.

3stacks 3mo ago

It’s the food equivalent of declaring bankruptcy. If you don’t fix the behaviours you’ll just end up in debt again.

kolinko 3mo ago
This assumes underlying behaviours are core reason. Research (tein, adoption) suggests otherwise
- yakz 3mo ago
  Practically speaking, any person could starve themself (short of death) and lose weight. In almost all cases there is no magic to storing more energy than you need.
  - shadowpho 3mo ago
    Practically speaking any person cannot maintain that for significant length of time. Dieting has like a 99% fail rate by year 2. It’s hard to maintain that for many people — your body will keep you in starvation mode, keep you hungry and hang on to every calorie received.

LaurensBER 3mo ago

I've gained and lost 10kg twice in my life. Maintaining the weight loss isn't that hard once you've a rhythm dialed in. In my case I just weight myself daily, track the weight and scale my food consumption with the current trend. If I'm gaining weight I'll skip a meal. It takes a while to figure out what works for you but I can tell you that making small lifestyle changes to maintain your weight is fairly easy compared to figuring out how to lose 10 kg.

kolinko 3mo ago
Just because it wasn’t hard for you doesn’t mean it isn’t hard for the others. Grom what you said it seems you just had some bad habits you had to fix and that’s it.
coffeemug 3mo ago
When I was lifting weights I went from 170lbs to 210, and back to 170. Doing that isn’t technically hard, and maintaining is even easier. But I had to think about it _all_ the time. Maybe it’s because I’m older now, but I just don’t want to spend that much effort thinking about food.
- faangguyindia 3mo ago
  lifting weight isn't efficient for weight loss. Without calorie deficit, you'll not lose much weight by lifting alone.
  - SoftTalker 3mo ago
    You'll probably gain weight in fact. Muscle is heavier than fat.

flextheruler 3mo ago

Unfortunately for a lot of people with weight issues it stems from becoming overweight during puberty which is uniquely bad. Your body's appetite signals are permanently impaired if you become overweight during puberty because during this window your fat cells don't just increase in size, but also in number and this increased quantity does not go away once created. Fat cell shrink as weight is loss, but they are not destroyed and they are responsible for appetite signaling. It's one of the reasons that childhood obesity is actually leagues worse than it first appears and I think should be considered child abuse in extreme circumstances.

apt-apt-apt-apt 3mo ago
What you said isn't unique to puberty, it's the same with being overweight in adulthood (AIUI).

SubiculumCode 3mo ago

And this morning, I cut another hole in my belt. Turns out, losing weight and being thin was never about willpower or laziness in the face of absolute food abundance. It was mostly about whether a person was born lucky enough to have a moderate appetite, or was born burdened by exaggerated appetite. The underlying issue is physiological food cravings, not some personal failing or lack of willpower, and GLP-1 absolutely addresses those "underlying issues". That it isn't some one and done pill is hardly a realistic expectation as that would require probably genetic and epigenetic reprogramming.

nihonde 3mo ago
The idea that appetites are assigned at birth is a bold claim. Is there evidence to support it?
- 9x39 3mo ago
  Well, not assigned by the hospital or your parents, but being a DNA-based lifeform a genetic baseline is a safe assumption. Experiences vary after that: https://pmc.ncbi.nlm.nih.gov/articles/PMC3052625/ https://pmc.ncbi.nlm.nih.gov/articles/PMC3052625/
  - s1artibartfast 3mo ago
    I think there is much stronger evidence that it is metabolic damage from overconsumption in an earlier stage in life. Not unlike if you shatter your legs, your recovery may be long and incomplete.
- SubiculumCode 3mo ago
  Genetics and epigenetic factors.
tedmiston 3mo ago
[dead]

aaron695 3mo ago

[dead]

fragmede 3mo ago

The drug stops working if you stop taking it? Shocking! Heart medication for hypertension also stops working if you don't take it. Sure there's a vast conspiracy by the pharmaceutical industry to hook us all on drugs because we can't learn to exercise, but that's hardly Ozempic's fault. Now if you were looking at brain surgery that zaps the reward center of the brain causing permanent changes so the patient was less addicted to food, but the patient kept needing to have brain surgery, then you'd have a point, but "drug stops working if you don't take it" is hardly the gotcha some make it out to be. Insulin also stops working for diabetics if they don't take it. That's kind of medication's whole deal. Now that we know obesity can be controlled via medication, and it'll cost $foo over the lifetime of the patient, the next step is to optimize. If there is a treatment involving ultrasonic brain surgery that costs less than $foo, the expectation is for the market to find that. Ultrasonic brain surgery is in its infancy, but it's already showing utility for Alzheimer's and addiction. The real question is if the pharma companies are going to be able to keep it from going mainstream because it's less profitable for them.

JumpCrisscross 3mo ago

> almost all subjects regained the weight and reversed gains within 2 years Source? I thought it was 2/3rds of the weight regained, which is still a substantial long-term loss.

shlant 3mo ago
supposedly that comes mostly from observational studies whereas RCT's seem to show that at some point full regain will probably happen (although can take 1-2 years). The Observational studies don't seem to control for people stopping GLP-1's but still trying other drugs/weight loss methods which is where the discrepancy from RCT's seems to be.
- JumpCrisscross 3mo ago
  > supposedly that comes mostly from observational studies whereas RCT's seem to show that at some point full regain will probably happen Do you have one you’d recommend reading?

SOLAR_FIELDS 3mo ago

Statins are a well understood mechanism of action for controlling cholesterol. We generally understand that people with cholesterol problems leverage statin therapy to address those, and there is a well audited corpus of placebo controlled double blind trials that demonstrate the efficacy of the solution for statin therapy. If you discontinue the statins, you lose the benefit to some extent. How is this situation fundamentally different?

tqi 3mo ago
Agree, same can be said of exercise. I think people consciously or unconsciously consider being overweight a moral failing and so are quick to point out the flaws.

mukbangpervert 3mo ago

What facts do you have that make you certain that the underlying issue is "food addiction" rather than, say, a difference in body chemistry that changes perceived hunger levels?

PaulHoule 3mo ago

It's not like anything else in terms of drugs, surgery, or lifestyle changes has been proven safe and effective. A person who is dependent on opiates or caffeine or cannabis can possibly live without those substances, you can't go "cold turkey" from food. Funny I just shot myself with a Zepbound autoinjector for the first time! My primary care doc told me he thought I was a good candidate a year ago but that he had trouble getting insurance to pay for it, it took me a year to get in with a specialist, insurance approved it right away, and now I am supposed to keep a food an exercise log. I am well in the obese BMI range but I've been active my whole life (e.g. I can't see how people can get through the day without going to the gym or something) so I have a high lean mass and don't look that fat with my clothes on. I've struggled for years with various conditions associated with "metabolic syndrome" and I'm on numerous maintenance medications already and may be able to delete some of them. I am currently around 250 lbs which has been my usual for the past 20 years or so. Had some luck with Zone, ketogentic and bean plan diets but couldn't stay on any of them indefinitely. Got my weight down to about 208 lb in six months when I quit taking antidepressants at my doctor's suggestion (never went back), had something like a manic episode where I manifested an "evil twin" who was vain highly motivated [1] and worked out like... a maniac and I also discovered I had TMJ dysfunction and took load off my jaw by throwing comically random food (cashews, seaweed, celery, potatoes, carrots, pork, ...) into a pot and grinding it with an immersion blended. Not sustainable, not least because my evil twin's antics got me kicked out of the gym. [1] as-a-fox one axiom is that "I never push on a string" and have a hierarchy of goals, non-goal goals and non-goals; my non-goal goals are his OKRs

dmayle 3mo ago

The issue isn't food addiction, it's a broken hunger response (broken by Howard Moskowitz intentionally in the name of profits)... You have to change your food regimen completely (higher fiber, more protein, less sugar, less carbs, less fat), and that's tough to do when you're surrounded by options that aren't... I think the real problem is that the symptom we're trying to treat is "overweight", and it's actually a two-stage problem... Fix the hunger response... and only then work on fixing the weight... Fixinig the latter without fixing the former means you'll always gain the weight back, fixing the former doesn't guarantee you lose weight (and is only temporary, if you're using drugs for it)... You have to go after both problems.

basch 3mo ago
We shouldn’t ignore grocery stores and marketing. Aisles and aisles of sugar drinks and colorful sugar packaging. The way society leaves it up to people to make their own decisions creates the problem at scale. Society essentially has to take weekly injections to avoid the temptation of coca cola.
mynameisash 3mo ago
What breaks the hunger response, and how does one fix it? Maybe it's well-known, but I read the starvation response Wikipedia page[0] and didn't grok it. [0] https://en.wikipedia.org/wiki/Starvation_response https://en.wikipedia.org/wiki/Starvation_response
- SoftTalker 3mo ago
  Buy unprocessed food and prepare it yourself. Don't add sugar. Eating processed food and even most restaurant food is eating food that's designed to make you want more, not satiate you.
  - mynameisash 3mo ago
    I guess I should have asked about the technical mechanism of what causes and what actually 'breaks', and then what the technical remedy is.

rfv6723 3mo ago

The only underlying issue is an evolutionary mismatch: human evolution is too slow to keep pace with the modern abundance of food. What we now call food addiction is exactly what kept our ancestors alive during famines.

epihelix 3mo ago

If your biology is working against you, why not fix your biology? I'm not someone who needs to take GLP-1 receptor agonists, but if I had any issues with weight then I'd have no issue taking them life-long. The long-term health benefits are already strong enough to make it a no-brainer. If you are overweight and a GLP-1 drug helps you lose that weight, you will very likely live a longer, healthier and happier life by taking the drug. All that said -- this article was discussing a new paper in Cell Host & Microbe (high-impact Cell Press stable journal), https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(26)00179-4 https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(2... . And the point of that paper is that, at least in mice, the anti-depressive effect of GLP-1 receptor agonists was related to a change in gut microbiota, and not to activation of the GPL-1 receptor. It's work in mice only, so whether or not this holds in humans is unclear, but the researchers showed this worked in mice lacking the GLP-1 receptor and via fecal microbiota transplantation of bacteria from the guts of mice taking GLP-1s. So, if all you cared about were the mental health benefits of taking GLP-1s, then potentially you could gain these by simply changing your gut flora, without taking a GLP-1 drug at all. That might sit much better with you, by the sounds of it.

port11 3mo ago
If the food abundantly available is full of unhealthy ingredients and nutrient combinations meant to make you addicted, why not fix that? We blame biology and people’s willpower a lot, instead of considering how plenty of other or previous societies don’t/didn’t have this issue.
- tqi 3mo ago
  The former isnt something an individual can change on their own

mullingitover 3mo ago

Diet programs as a weight loss strategy are utter failures, and it’s malpractice to push them as a treatment. Yet there are still people pushing them as something that’s perfect, if only you didn’t screw them up. When a treatment can’t fail and can only be failed, it’s big red flag for me.

thaw13579 3mo ago

The issue is that our modern world has engineered our food to be highly energy-dense and incredibly appealing, so the root cause is an evolutionary mismatch with our environment, which has diverged incredibly from early humans. Personally, I look at GLP-1 agonists as akin to wearing glasses. Some people are just born without the ability to regulate their appetite in accordance with our society, but there is a tool / prosthetic to change that, often that's a lifelong solution.

sakopov 3mo ago

Does loss of muscle mass, commonly associated with Ozempic weight loss, become an issue after regaining the weight? Can it result in proportionally more fat at the same body weight as before if exercise wasn't part of the regiment?

theshrike79 3mo ago
_All_ weight loss results in loss of muscle mass unless you do something about it. If you ingest less calories, you lose both muscle and fat mass.
amanaplanacanal 3mo ago
I believe loss of muscle mass is commonly associated with other weight loss methods too. It's not just ozempic. You need protein and exercise no matter how you are losing weight.

teliosix 3mo ago

Totally agree. My father is 75 and started taking GLP1. He stopped drinking immediately, lost 25lbs already and I can't imagine hasn't already added some time to his life. The calculus at 75 is much different than at 35 in terms of what "for life" means. It seems like there could be an issue too that it just stops working that well 10 years down the road. Not an issue for my father at 85 the way it would be for someone at 45.

whazor 3mo ago

What were the numbers again? Because I remember a significant amount of people actually did not regain weight. Although the majority did.

amunozo 3mo ago

But it does sit well with pharma companies.

theshrike79 3mo ago

Blood pressure and high cholesterol can both be genetic. So people just are on meds for both all their life. It doesn't cure anything - it's not supposed to.

QuantumGood 3mo ago

The "here's where you're getting it wrong" discussions on glucagon‑like peptide‑1 receptor agonists are paralleling AI discussons. Interesting to watch these two domains of knowledge sparking (mis)framing arguments happening at roughly the same time.