Kind of a useless analysis if it doesn't compare the risk after stopping GLP-1s to the risk of NEVER taking GLP-1s in the first place.
We probably don't know the numbers yet, but one can easily envision a scenario like: risk of CE without GLP-1 weight loss: 20%. Risk after taking GLP-1s for 2 years: 10%. Risk after stopping GLP-1s: 12%. "Your heart attack chance goes up 20% after stopping GLP-1s!!!"
The data on the results section shows almost parity between the control group and participants who discontinued for 2 years.
Note that while it is a well conducted study at the US VA with 300,000+ patients, it is not a randomized study so fully eliminating confounding variables and reverse causality is hard.
There is a recent one, which shows that the weight was generally stable after 1 year of discontinuation of GLP-1.
> In this cohort study of adults with overweight or obesity who initiated treatment with injectable semaglutide or tirzepatide and discontinued the index medication between 3 and 12 months after initiation, 19.6% restarted the index medication and 35.2% received an alternative treatment in the year after initial treatment discontinuation. The average weight change 1 year after index medication discontinuation was relatively small; however, there was considerable individual-level variability.
Thanks for sharing. Note that the data quality from this study is quite low because 54.8% of the cohort eventually restarted their medication or transitioned to an alternative therapy (mostly a different weight loss medication).
I don't know why a study that focuses on discontinuation didn't split the groups that restarted or transitioned against the group that actually just stopped.
The discontinued and paused groups in the actual study had lower BMI than the continuing groups - so it seems like this is at least partially independent of any weight regain.
Which makes sense since we have strong evidence for the GLP-1s providing significant protective benefit even without weight loss.
Scientifically it's valid, and good scientists and doctors would immediately pick up on the nuance.
The issue is shameless "science" reporting like this which packages up the results for non experts, without explaining the nuance because they know the sensational headlines will get more attention, and they know non-expert readers will get scared and share the article on places like HN or Facebook.
It's such an obvious play: find one doctor who'll make a loaded statement with the word "whiplash", write on this one study as if it's gospel truth, get everyone reading it as scared as possible. Throw in links to other emotional articles like "Can you die of a broken heart?" throughout the text to trigger secondary emotional reactions that will get confused with the main ones. Boom, social media sharing heaven, who cares if the science was valid or not?
And to be clear, the science underneath might be valid, probably even is, but it would need the expertise of someone who understands statistics and medicine to decide whether you should take action based on this or not.
This is a very odd phrasing that makes it seem like heart attack and stroke risk are higher for those who stop taking the drug than those who never took the drug. Moreover, the effect of restarting taking the drug seems attributable to the study design. Those who took a break had higher risk at the end of the study than those who don’t. But those who took a break took the drug for less total time than those who took it for the entire study.
You could characterize these same facts in the opposite way. GLP-1s don’t permanently change your body. They provide benefits while taking them but quickly clear out of your system when you stop taking them. Arguably, that’s a good thing in a drug.
>This is a very odd phrasing that makes it seem like heart attack and stroke risk are higher for those who stop taking the drug than those who never took the drug.
That does appear to be the case, according to the study.
It certainly does not. To make that claim, the study would need a control group of people who had never taken the drug. They didn't have that:
> Participants Veterans Affairs users with type 2 diabetes who started treatment with GLP-1RAs (n=132 551) or sulfonylureas (n=201 136), followed up for three years. Veterans Affairs users were defined as having at least two visits to Veterans Affairs and having used the Veterans Affairs outpatient pharmacy within a year before receiving treatment with GLP-1RAs or sulfonylureas.
So, why not? Seems very obvious to everyone here on HN that it's "kind of useless" unless they did have that, yet they didn't. What reason would there be for ignoring that?
They were testing what happens when you stop taking Ozempic compared to what happens when you don't stop taking it, and also what happens when you start taking it again.
Assembling a control group of people who have never taken Ozempic could be difficult. How do you control for the fact that people not on Ozempic are less likely to need Ozempic? You'd need to figure out some criteria by which to include and exclude patients before sorting by whether they take Ozempic or not, so you'd have a smaller sample size of people who are taking Ozempic.
> This study showed that discontinuing and interrupting GLP-1RA treatment could erode and might reverse the cardiovascular benefits of the drug in a duration dependent manner, increasing the risk of cardiovascular events.
I’m always kind of envious of the people who were able to lose weight on GLP-1 drugs. I lost a bunch of weight a few years ago, and still need to lose a lot more (430 lb -> 330, goal 240), but I fell out of the good habits for, well, no good reasons…
Decided to try Ozempic and was on it for about 6 months. Didn’t do a single thing for my appetite unfortunately, even on the max dose.
Sample size of one here, but if you’ve got mental health struggles that feed into your eating patterns, GLP-1s might not help with your weight problems.
Wegovy/Ozempic didn’t do anything for me for months. Then my doc put me on Tirzepatide+Phentermine combo and I forgot what being hungry even feels like.
I couldn't hit my macros on tirzepatide - couldn't get enough protein without feeling sick to my stomach. One of the reasons I swapped to reta.
(though as a general note for anyone reading, just getting enough protein isn't enough - you need muscle stimulus too. Getting enough protein will help reduce the amount lost but if you really want to stop it, you gotta do resistance training)
It lets me more or less skip a meal but holy hell I am craving sugar more than ever. On the whole I'm cutting calories and have lost a lot of weight, I just wish I didn't want sugar this much.
I’ve always been more of a savory kind of person myself. I’d take biscuits and gravy or a steak over sweets any day!
But I feel you on sugar. Took me a long time to cut sugar cravings. A decade ago I cut regular soda out of my diet, which a few years later led to me cutting out pretty much anything sweetened. Realistically it wasn’t the sweetness for me, it was the “mouthfeel” or doing something with your mouth. Just straight sparkling water satisfied the entire craving for me.
The hardest thing for me to give up / heavily cut back on was fried things. Maybe that’s the result of my parents using french fries as the reward food when I was a kid…
Try allulose-sweetened stuff. Allulose is a sugar your body doesn't metabolize like sucrose. It has zero calories and does not increase your blood sugar. It's a component of maple syrup and so does taste a bit maple-y, but better than most artificial sweeteners and even stevia leaf extract (stevia and aspartame have a "tang" to them I dislike).
That's unfortunate! It might be worth checking out Tirzepatide or Retatrutide once it is released. The GIP and Glucagon receptors might be better targets for you, even if the GLP-1 receptor seems to not help.
I really had thought (with no research) the correlation between mental health and glp1 effectiveness went the other way around. Thank you for this check-your-biases moment, you probably just saved me a ton of embarrassment down the line, if these drugs ever enter my life.
You missed out on both of the weight suppression tricks, which really does suck. Appetite suppression (or reduction of food noise) is pretty useful, but GLP1s also tend to punish you mightily if you overeat. For me, even if I were hungry, overeating will make me hurt for hours. I could not gain weight on this even if I wanted to.
There are some difference, too, between the various drugs. I never tried ozempic, I went directly to tirzepatide (zepbound). And then to retatrutide. I will say that reta is in some ways the most interesting, because it has less appetite suppressing activity than tirzepatide (this is common, not just me), but it still cuts my stomach capacity quite a lot, and ramps up my metabolism. I had stalled at about 90 pounds down with tirzepatide, and reta immediately knocked off another 15. I track calories, and I had changed nothing. Felt more hungry, still lost more weight. Wild.
From one rando to another, I recommend trying tirzepatide. Or try semaglutide again but stacked with cagrilintide -- some people get pretty great results with that, similar to tirz.
Yeah I might just have to go get it out of plan. Kaiser covers Ozempic, but none of the Tirzepatide based medications. (Edit: looks like that might have changed)
I am a big guy (6’4, 330 lbs), but I was amazed that Ozempic just seemed to do nothing. I was having the gastric side effects, but I could still eat 3000 calories a day if I cheated without feeling anything.
Similar experience here with Tirzepatide. Overeating is punished swiftly and painfully.
If it works for you, look into getting one of the 15mg pens and counting clicks in order to get more doses per vial. I've been on the one pen for 3 months now and it's still got plenty of juice left.
One of the quirks of buying brand name GLP1s in the US is that we don't get the dial-a-dose pens, every autopen is one-shot. Some people disassemble them to get multiple doses, but at that point you might as well get the cheaper brand name vials or go with compound or gray.
When I was on Ozempic in the US (Bay Area), it was a dial-a-dose Ozempic branded pen. Came with 4-6 single use needles you’d screw onto the end before use, and discard into a sharps bin after.
Which do you like? Barebells salty peanut and chocolate dough over here. Though the sugar alcohols certainly aren’t great for you either, I think they were recently linked to stroke risk
I went down from 390lbs to 240lbs gradually over 5 years. I have maintained a weight of 240lbs since then (6'1" tall).
The first year was the most dramatic loss of 100lbs. I was miserable and didn't know what I was doing other than counting calories. The rest of it was more considerate of total nutrition, and that's what made my good eating habits stick.
I say this because while I'm not a doctor I think GLP-1 is probably unnecessary for the vast majority of patients. Better food and information is more available than ever before.
I would strongly advise to watch your A1C and get out of the diabetes danger zone if you are. Most people can drop a few percent in as little as 6 months and it makes a massive difference in mental health. Blood glucose has a direct impact on the brain and overall cardiovascular health. If you drink alcohol, you might want to take a break also to let your liver/kidneys/pancreas do their jobs properly and restore insulin sensitivity and other hormones. Look into the "fruit paradox", and more generally get a good salad in for lunch to address nutrient deficiencies. Not crappy salads either. You're not a rabbit. Treat them like the amazing sandwiches without bread that they are.
Sounds like old advice, because it is, but I find people aren't listening because they want to more deeply understand why to do it and what the effects are. Convenience and unintuitive pricing are false bargains that get in the way of healthier habits. Focus on nutrition and not quantity. Change your groceries, change your life.
> I say this because while I'm not a doctor I think GLP-1 is probably unnecessary for the vast majority of patients.
We have mountains of evidence that willpower fails for something like 99% of everyone, which is far from a vast majority. I applaud anyone's efforts to become healthier, however (though 240 at 6'1" is still obese, I would still explore medicine if I could not get any lower "naturally").
Thanks for the reply. Your perspective framing this as "willpower" is precisely what I'm concerned about.
I didn't need any willpower to do this and I'm not even humblebragging nor think of myself as a tough guy. I'm saying that healthy habits are simply a matter of understanding. If someone wants to take GLP-1 on top of that, it's their call. Many seem to be under the impression it's so vital for their specific situation to lose weight or avoid a heart attack and I think that's plainly false. We shouldn't be feeding fear, and humans aren't that unique.
I did not change my diet. If anything I just added more variety with a specific intent and it worked. Even just changing the order in which one eats things (fiber before sugary foods) can make a big difference. Once I got the blood glucose under control all the strong cravings and eating mistakes basically went away on their own without my conscious effort. The body is all connected and driven by hormones.
Sorry, you're right. I meant that I did not make significant changes to my diet. My point was I didn't really change what I eat, but how I eat. I still hate certain vegetables like carrots, kale, brussel sprouts, etc. and just added more of the nutritionally equivalent and culinarily far superior vegetables I was already eating.
That's not willpower. That's looking things up in the USDA database and tweaking my existing recipes. Why force nasty carrots onto the plate when I can eat spinach, cantaloupe, pumpkin, sweet potato, etc.?
I guess I also didn't emphasize enough that I took things super slowly? Taking 5 years to do what I did is a really modest goal. I just wanted to manage risk with minimal change. This is the pareto principle in action.
If we're really going to argue over stats, the effects of GLP-1 is meaningless noise in comparison and probably way harder to commit to. I just wanted to eat good and not feel like shit all the time. Isn't that what everyone wants? What if instead of there being "one weird trick" or a "miracle drug", we consider that basic nutrition is simply misunderstood and full of hundreds of weird tricks that are proportionally much easier to implement and they're damn tasty too?
I'm not knocking anyone meeting their goals without GLP-1s. It's obviously possible in absolute terms - people have been making great body transformations for as long as we've had fat people.
But everything you did, plenty of people try to do and fail at it. You are making it sound like this is all it takes and that it's easy. It might have been for you! But it might not be for other people.
The fact of the matter is the overwhelming majority of people that are obese and go on GLP-1s have tried other interventions before and failed at them. ~70% of all obese people have tried to lose weight in general, ~50% have recurring attempts, and while I don't have stats to back it up I am confident that the sort of people who are willing to go and inject themselves every week are the sort of people that have tried to lose weight in other ways.
> probably way harder to commit to.
A subcutaneous injection once a week is nothing. Dealing with constant food noise? I could maintain that if the rest of my life was stress free, and that's how I would drop 30lb. Once stress came back? So did the weight. Because for me, rearranging food doesn't matter if I still can't stop thinking about it even if I'm not actually hungry.
I'm on reta. It does barely anything to suppress my appetite - physical hunger has never been my issue. And I can easily eat however much I want - most days I am below 2k calories, but Saturday was an annual event with friends and I'm sure between food and alcohol I was probably at 5k calories for the day. But what reta does, is absolutely murders my food noise. I don't think about food constantly. I don't go eat because I got bored. The only thing I have to commit to for it is, once a week, put a needle on my injector pen, twist the dial to the right dosage, poke it into a spot where I still have subcutaneous fat, depress the twist top. Once a month I reconstitute a new vial.
I do at least one a day, sometimes up to four if things happen to line up exactly right.
Even four subq injections amounting to around 2ml of stuff is nothing, doing all four of them after a shower takes about as long as brushing my teeth.
If you use correct technique and good quality needles, you will feel essentially nothing. If your needles are not sharp enough, there might be very slight discomfort when initially piercing the skin.
The actual study states in the summary that it's the cardiac protective improvement that reverses, not that you're worse off for having taken a GLP-1.
So yeah, when you stop taking something that protects your heart and kidneys, it stops protecting... your heart and kidneys.
There's an increasing body of work that indicates that long-term GLP use (initially higher doses for weight loss, then tapering down) retains the cardiac and kidney benefits and can actually lead to additional weight loss.
It doesn't reduce heart attack and stroke. It reduces appetite, kind of, and gives you a sore stomach while making you shit yourself inside out. All this can, with care, help contribute to weight loss.
Weight loss can reduce heart attack and stroke, but GLP-1 does not.
You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often.
We see risk reduction for heart attack and stroke for people on GLP-1s even without weight loss, which belies the idea that the protection only comes from losing weight.
Edit:
In fact, from the study -
BMI went from 35.86 (Continued) to 34.57 (Discontinued) to 35.48 (Interrupted),
Heart failure percentage was 11.57% for continued use, 12.73% for discontinued, 11.92% for interrupted
NICM went 3.10% for continued, 3.36% for discontinued, 3.31% for interrupted
BMI was higher for the continuing users and they still had lower heart failure and NICM rates than the discontinued and interrupted groups. (Also a bunch of other things including stroke and heart attack but I didn't want to write all of these out)
As best as I can tell, people are very attached to having achieved their body weight through whatever means they have determined are valid and derive self value from it, and believe that GLP-1s are cheating to achieve a result they worked harder for.
What you need to understand is there are a lot of people where all they have is being skinny and appearing to be healthy. Without that, there's nothing left for them.
For a long time, there has been a moat that they can use as a justification for why they're better. They can say "well I work hard, I eat right, I put in effort!" The idea that others can achieve that without any of that means... well, they did it all for nothing. In their heads.
The dirty little secret? Many of them don't do any of that, it's just a delusion. Always has been. I'm skinny, you think I go to the gym? Fuck no! I should, but I don't. And I eat whatever I want.
But if a lot of people have to face the reality that their most redeeming quality is nothing of their doing, that would ruin them. Ruin them. They could just, like, get achievements or something but that's hard. Continuing the delusion is easy.
Pretty much every adult fat person has attempted diet and exercise to resolve their weight issue.
Saying they should try this first at this point in the game is like having your support case escalated 5 times already and them saying "have you tried turning it off and on again"
It does reduce your appetite, and for most people have very few side effects. If you get nausea you're titrating up too fast. Most people, because it slows gastric emptying, it doesn't make them shit themselves "inside and out". GLP1s are a decent option for treating ibs-d or bile acid issues and is better tolerated than your bile acid sequesterants.
> You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often.
This victim blaming advice has been given for decades and obesity rates have been climbing for decades. Only glp-1s have reduced that.
Isn't GLP-1 creating a "feel-good" starvation? Patching the receptors telling the brain one is not hungry and then just letting the body starve happily, leading to significant muscle loss and aged face? Contrary to e.g. water fast where the body switches to 100% ketosis that can run as long as there is any fat in the body and one supplements electrolytes (Mg/K/P/HCO3) and vitamins (predominantly B1/B2/B3), leading to a much more healthy appearance?
GLP1s do not themselves cause any worse muscle loss than you would experience if you lost the weight by watching calories the old fashioned way.
"Ozempic face" is almost certainly an artifact of people who spent their life significantly overweight having somewhat looser skin than they would if they had maintained a low weight throughout their life.
Also, not everyone gets the face effect, not by a long shot.
Not really, Ozempic face is the same face as one gets when starved of food for a longer period of time from low caloric diet that contains carbs. Ketosis on the other hand doesn't cause this unless one has almost no fat left as it doesn't switch body to the starvation mode.
There are two modes the human body operates normally - insulin-driven, active when carbs are in the food, and ketone-driven, active when there is a lot of fat storage and no food intake, or food has no carbs. Insulin-driven operation switches to starvation when food intake has caloric deficit but still enough carbs for insulin to be triggered; ketones on the other hand lead to zero insulin activity and pure fat burning; starvation is only activated when humans reach around 4% body fat while in ketosis.
"Starvation mode" as people talk about it is generally nonsense - the exceedingly low bodyfat you mention for keto is the same place you would see it in a non-keto diet when we talk about actual starvation mode and not whatever you're talking about with a non-ketogenic diet.
The only real difference when it comes to the biology here is that fat mobilization into glucose is significantly slower and less efficient, which keeps your blood sugar levels more constant, which results in fewer post-meal food cravings. Which isn't nothing, but it's not muscle sparing in and of itself.
We have plenty of studies here. Keto diets are not better for sparing lbm.
In fact, if you already have significant muscle mass, it might be worse. Glycogen is hugely important when doing resistance training, and keto significantly impacts your glycogen stores. People perform worse with their resistance training on keto than regular diets.
I suspect you have no idea that your body has two independent energetic circuits - one driven by insulin and glucose, the other driver by ketones. Just please dump this to any decent LLm to give you ELI5. Muscles obviously need glucose for their best performance which is why strength training is not recommended during ketosis; OTOH ketosis is naturally muscle-sparing.
> I suspect you have no idea that your body has two independent energetic circuits - one driven by insulin and glucose, the other driver by ketones.
I am fully aware - I have spent several years of my life following a ketogenic diet. None of that is relevant for "starvation mode" and insulin within that context. I was replying to your specific points - not providing an explanation on how ketosis works from end to end.
Unless you are claiming that your body just doesn't produce glucose/glycogen and insulin when in ketosis? Which would also be incorrect.
> Muscles obviously need glucose for their best performance which is why strength training is not recommended during ketosis;
Strength training should 100% still be done in ketosis/while following a ketogenic diet. It will be suboptimal compared to a regular training, but being in ketosis doesn't magically make resistance training optional if you want to be healthy.
> OTOH ketosis is naturally muscle-sparing.
It is not and the study links in my post show consistent data here. There might be an exception if you are an endurance athlete but that is based on far more limited data than the rest of the research. So... if you're a high level endurance athlete that is also somehow fat, keto might be a better option when it comes to sparing muscle, but for the rest of us, not the case.
Yeah exactly, what people call Ozempic Face is often just wrinkles. I look a bit older now that I lost 40 lbs, but much healthier shape. Fat does fill in your face some
Muscle loss is determined by your protein intake, muscle stimulus, and rate of weight loss. Plenty of people start lifting for the first time (or after having stopped for extended periods of time) when going on GLP-1s and actually put on muscle mass.
It might result in more loss of buccal fat than otherwise but even that is not definitive. Activating the receptors is not the same as burning fat - there are GLP-1 receptors all over your body in all sorts of organs. If you activate them in your brain you're not burning your brain for energy.
n=1, been lifting weights for 25 years and lost 40 lbs on Zepbound and counting.
I can still do my routines easily with no issues. My muscles look slightly smaller I think, but maybe that's the fat around them that's been diminished.
"Emerging research suggests GLP‑1 receptors are present on adipocytes and fibroblasts. Some animal studies indicate that GLP‑1 agonism may promote lipolysis in subcutaneous fat more aggressively than in visceral fat, leading to disproportionate loss of facial fat. It also may affect collagen synthesis or skin architecture, though human data are still evolving."
How much of this could attributed to simply having less artificial hormonal support for not overeating after discontinuing treatment, and falling back into old habits? I’d love to see more research focused on these mechanisms.
> To find out what happens when people stop taking GLP-1s, Al-Aly’s team of researchers tracked the health of more than 333,000 United States veterans with type 2 diabetes for three years.
Also News I guess - People who pick up smoking again after a period of cessation, regain all negative effects of smoking that they previously experienced during that past smoking periods, eliminating the positive effects of the smoking cessation.
I mostly feel bad for job losses due to AI, but I won't shed a tear for journalists who make a living spreading misinformation about the results of research.
> They found that the risk of heart attack and stroke jumped in those that paused GLP-1 treatments for as little as six months, compared to those who continued taking the medication.
(Emphasis mine) The 'jumped' would more correctly say 'tended to revert to baseline' if you just had a basic LLM summarize this study for you...but then that wouldn't drive clicks and shares on your article.
Honestly don’t understand it. Feels like a lack of discipline. I was 250. Plugged in a bunch of numbers into an app and it gave me a calorie count per day. I brought a scale with me everywhere, used ChatGPT to guesstimate calories, I added 50% for good measure. A year later I’m 175. You can’t do this even with drugs you’re gonna get fat anyway.
I’m most curious about someone like me vs someone who lost the same amount on glp1 with respect to these stats
A decade or so ago, when I was still in uni, I managed to get similar results naturally too - ~100kg down to ~65kg in around 18-24 months just by eating healthy and exercising more.
I put back all of that weight and then some during the COVID pandemic (I'm in Melbourne, Australia - we had the worst lockdowns on planet Earth) and this time struggled for years to lose it until trying GLP-1 drugs a few months back.
For me, what made it harder the second time around wasn't so much of a difference in discipline skills (if anything, they've improved) but the fact that there was so much more going on in my life - young family constantly getting sick, small business that started struggling, relationship/social issues, health issues (sleep apnoea) etc. etc.
I'd get on the weight loss train, lose a couple of kilos, then the whole family would get sick with the flu and I'd put it all back on again while recovering. Or maybe I'd be forced to shift my focus to the business so that we could keep the lights on. Or any number of things.
I guess my point is that it's not difficult to lose weight naturally (or any self-improvement, really) in and on itself, but it's completely different ballgame when you're fighting a war on 6 different fronts. Having one of those problems simply just disappear through GLP-1 drugs genuinely feels like a miracle.
We know that GLP1s have benefits that are disproportionate with just weight loss, so someone who is otherwise like you in terms of weight loss would probably have better cardiovascular markers.
Probably the biggest difference, though, is that an average "you" will be back at original weight, plus a little, in about a year, while the average GLP1 user will (assuming they keep taking it) be the same weight, or even a bit lighter.
Everything is discipline. If you just always do the thing you’re supposed to you will win at life. People can’t always do the thing they’re supposed to so they supplement with drugs that help them do it: caffeine, amphetamine, SSRIs, GLP-1RAs and related drugs.
In fact, everything is discipline. If you were disciplined enough to always put the basketball in the net from anywhere on the court you’d be Steph Curry. The thing is most people don’t have that kind of discipline. Someone runs up to them and puts their hand up in the air? They shoot wide or balk. Curry shoots true. Discipline.
Just always do the right thing and never do the wrong thing and you’ll be fine at literally everything.
Weight loss of course is helped by talent, because genetics are talent.
Metabolisms fluctuate, although granted not by much. But what really varies is your response to food. And it's not just genetics. It's food scarcity, early childhood, your environment.
The (maybe) sad reality is that there will be people skinnier than you will ever be who have put in zero effort. Nada. That's life. Just like there's people who can sing better than me off the rip and I took vocal lessons for 10 years. Life's not fair.
But the bright side is, I can drink and not be an alcoholic. Maybe they're just lazy or something. Or, maybe this mentality is one people feed themselves (ha) to feel better about the circumstances of their life.
Wouldn't we all like to believe we're the way we are because we're strong, brave, and hard-working?
If you can be disciplined about taking a drug you can about food. How do you explain correlations in obesity across cultures? Genetic superiority? Again, imho just making excuses for laziness. The same logic you’re applying here also applies to even taking the drug and picking up refills from the mail…
Also look at obesity rates across time within the same country. It’s clearly not an issue of discipline, it’s an issue of what’s being eaten.
Why in the world do you think that taking a once a week injection requires even remotely similar levels of discipline to dealing with daily hunger and food noise? There's like, a dozen orders of magnitude in between. This is a silly argument.
> How do you explain correlations in obesity across cultures? Genetic superiority?
Every developed nation in the world except Japan has been seeing obesity and overweight rates rising at significant rates, including countries that have fairly similar cultures, such as Korea. You also see people move to America and stay in relatively isolated pockets of their culture and still gain weight.
So no. It's a matter of access to hyper palatable calorie dense food. The more of it around, the more likely people are to get fat. The fatter you get, the more of a feedback loop you end up in for a wide variety of known and relatively well understood mechanisms. GLP-1s help short circuit that feedback loop.
> Now there’s something we agree on. If only we could agree that no one is stuffing cheeseburgers down people’s throat other than themselves. So close.
No one is saying that it is forced. What I am saying is that your sense of moral superiority for the fact you aren't is misplaced.
Let's give you an anecdote: Up until 18 or so, I was a stick. I went from being a stick to getting into powerlifting. I spent the first chunk of my 20s with a pretty great physique. Then as I had more and more responsibilities in life, I had less and less bandwidth to apply to things like cooking, exercise, etc. I slowly lost muscle mass. I slowly gained fat. I had never had food noise when I was skinny - I had never compulsively felt the need to eat, regardless of hunger. I had never had food just constantly occupy my brain. After my slow descent into obesity, something fundamental about my relationship with food had changed. When my stress was lower and I was skinny or later fit, staying that way was easy. It didn't require great mental fortitude, massive discipline, any of that. And when I got fat, it wasn't because I was craving food - it was because I had shit to do and couldn't take the time to cook. Or because I was going outwith friends or my SO and eating out was a huge part of my social life.
When I looked at myself and decided I had to change, I though I just needed to stop doing those things. Stop going out, force myself to take the time to cook and let other things fall on the backburner, etc. Except now I thought about and craved food in a way I never had before. I went from thinking exactly the same as you to realizing 'Oh shit. This wasn't as simple as I thought it was.'
I lost weight plenty of times. Significant weight - not just a few lb, but 30+. Multiple times. And then I'd get busy at work, I'd have family members going through problems and need help, I'd have a rough patch with an SO - as soon as my mental bandwidth got divided, the weight loss stopped and regain started.
Even if an individual is just always able to resist, it's almost entirely based on their genetics. If you want to feel superior because of something you had no control over, I guess that's your perogative.
> Once the shame around disgusting fattening food has reached a critical mass the problem will solve it self.
I think shame is a useful human emotion. We evolved it for a reason. But we also know that it has limits and that once those are reached more shame on top, it becomes counter productive.
> Ironically the excuses you make for them only worsen the issue. If fat people and the food they ate were appropriate shamed they both would cease.
No. Fat people experience plenty of shame, and for a huge amount of them, it only worsens the problem. Once you shame a person too much - once you make it about them and not about the action - they start to feel that they are unable to make a change because they have less worth than those people that can, and often end up losing even more control in their relationship with food or whatever else they are being shamed about.
> FYI in Japan fat people are ruthlessly bullied. Fat people are rare. Food for thought, pun intended.
This is not universally true - it is highly regional, though the most populated portion of Japan is definitely an area where this is largely the case. But even in areas where this is not the case, they still have significantly lower obesity rates. Osaka and Hokkaido are significantly more laid back about it than the Tokyo area, for example, but they still have relatively flat obesity rates.
Basically every fat person in the developed world receives more than the maximum effective dose of shame over their body and it hasn't made them stop being fat.
You just have to be disciplined to always shoot accurately at the basket. Most people send it one way or the other but if you are disciplined enough in your aim at the basket no matter the constraints you will be the best basketballer of all time.
This makes it even more fantastic that the supply of GLP1s from my country's only legal importer is spotty and I've been suddenly cut off twice already
HN felt like one of the last places on the internet I could have good-faith conversations with intelligent people who would form thoughtful, on-topic replies.
And now it feels like the user base here has shifted enough that the voting system no longer consistently elevates the interesting comments, but the comments that reinforce people's worldviews.
Everyone feels Eternal September sooner or later. I recommend blocking users on this site. Having hit about 800 or so blocks I find that the conversation quality has skyrocketed. You still get one or two low quality users on a thread like this (I hadn’t blocked this guy) but the truth is that it’s usually a few people.
Any time a user gives me a flash of annoyance with a nonsensical comment that’s the last time I see them. This isn’t a native feature but Claude will implement it for you in a really short amount of time. If you want a feature set to copy or a list of users to seed, you can just copy mine (in profile).
Yeah, unfortunate that it's come to that, but I think you're right.
I started to write a comment about having some (additional) ideas for a Chrome extension, clicked your profile, watched the YouTube video. Fantastic. I think it already does everything I wanted.
Everyone feels this way about HN at some point, it is normal. It is probably true that the user base has grown and so you see more low-value comments in absolute numbers as time goes on, but I still think the overall quality is decent and the community moderation solid.
It is also a Friday afternoon, and HN's weekend (and to some extent overnight) 'personality' is noticeably different than during typical business hours. I enjoy coming here on weekends but it gets a bit more wacky.
Not if having a heart attack within 1 year at a higher rate is an co-morbidity factor when the primary treatment was for obesity or diabetes (not stating that obesity and heart disease are not positively correlated).
To use a dense analogy: if I stopped brushing my teeth I would not expect to die of gum disease.
You are misunderstanding the study (largely because the article heavily misrepresents it, would be my guess)
They do not see an increase against their pre-GLP1 baseline risk - they see a reversal of the cardioprotective benefits the drug provided while they were on it.
Kind of a useless analysis if it doesn't compare the risk after stopping GLP-1s to the risk of NEVER taking GLP-1s in the first place.
We probably don't know the numbers yet, but one can easily envision a scenario like: risk of CE without GLP-1 weight loss: 20%. Risk after taking GLP-1s for 2 years: 10%. Risk after stopping GLP-1s: 12%. "Your heart attack chance goes up 20% after stopping GLP-1s!!!"
They actually do compare against a control group. This is the study that is being referenced.
https://bmjmedicine.bmj.com/content/5/1/e002150
The data on the results section shows almost parity between the control group and participants who discontinued for 2 years.
Note that while it is a well conducted study at the US VA with 300,000+ patients, it is not a randomized study so fully eliminating confounding variables and reverse causality is hard.
Especially since every GLP-1 study shows almost complete regain to original weight after stopping.
It’s like stopping a blood pressure medicine and then being surprised that people have more heart attacks afterwards.
There is a recent one, which shows that the weight was generally stable after 1 year of discontinuation of GLP-1.
> In this cohort study of adults with overweight or obesity who initiated treatment with injectable semaglutide or tirzepatide and discontinued the index medication between 3 and 12 months after initiation, 19.6% restarted the index medication and 35.2% received an alternative treatment in the year after initial treatment discontinuation. The average weight change 1 year after index medication discontinuation was relatively small; however, there was considerable individual-level variability.
https://dom-pubs.pericles-prod.literatumonline.com/doi/10.11...
Thanks for sharing. Note that the data quality from this study is quite low because 54.8% of the cohort eventually restarted their medication or transitioned to an alternative therapy (mostly a different weight loss medication).
I don't know why a study that focuses on discontinuation didn't split the groups that restarted or transitioned against the group that actually just stopped.
The discontinued and paused groups in the actual study had lower BMI than the continuing groups - so it seems like this is at least partially independent of any weight regain.
Which makes sense since we have strong evidence for the GLP-1s providing significant protective benefit even without weight loss.
It's not useless. It might be expected, but now it's more certain. This allows planning with it.
Scientifically it's valid, and good scientists and doctors would immediately pick up on the nuance.
The issue is shameless "science" reporting like this which packages up the results for non experts, without explaining the nuance because they know the sensational headlines will get more attention, and they know non-expert readers will get scared and share the article on places like HN or Facebook.
It's such an obvious play: find one doctor who'll make a loaded statement with the word "whiplash", write on this one study as if it's gospel truth, get everyone reading it as scared as possible. Throw in links to other emotional articles like "Can you die of a broken heart?" throughout the text to trigger secondary emotional reactions that will get confused with the main ones. Boom, social media sharing heaven, who cares if the science was valid or not?
And to be clear, the science underneath might be valid, probably even is, but it would need the expertise of someone who understands statistics and medicine to decide whether you should take action based on this or not.
This is a very odd phrasing that makes it seem like heart attack and stroke risk are higher for those who stop taking the drug than those who never took the drug. Moreover, the effect of restarting taking the drug seems attributable to the study design. Those who took a break had higher risk at the end of the study than those who don’t. But those who took a break took the drug for less total time than those who took it for the entire study.
You could characterize these same facts in the opposite way. GLP-1s don’t permanently change your body. They provide benefits while taking them but quickly clear out of your system when you stop taking them. Arguably, that’s a good thing in a drug.
>This is a very odd phrasing that makes it seem like heart attack and stroke risk are higher for those who stop taking the drug than those who never took the drug.
That does appear to be the case, according to the study.
It certainly does not. To make that claim, the study would need a control group of people who had never taken the drug. They didn't have that:
> Participants Veterans Affairs users with type 2 diabetes who started treatment with GLP-1RAs (n=132 551) or sulfonylureas (n=201 136), followed up for three years. Veterans Affairs users were defined as having at least two visits to Veterans Affairs and having used the Veterans Affairs outpatient pharmacy within a year before receiving treatment with GLP-1RAs or sulfonylureas.
> They didn't have that
So, why not? Seems very obvious to everyone here on HN that it's "kind of useless" unless they did have that, yet they didn't. What reason would there be for ignoring that?
They were testing what happens when you stop taking Ozempic compared to what happens when you don't stop taking it, and also what happens when you start taking it again.
Assembling a control group of people who have never taken Ozempic could be difficult. How do you control for the fact that people not on Ozempic are less likely to need Ozempic? You'd need to figure out some criteria by which to include and exclude patients before sorting by whether they take Ozempic or not, so you'd have a smaller sample size of people who are taking Ozempic.
Best not to allow scope creep.
The conclusion of the study says:
> This study showed that discontinuing and interrupting GLP-1RA treatment could erode and might reverse the cardiovascular benefits of the drug in a duration dependent manner, increasing the risk of cardiovascular events.
emphasis mine
Reverse the benefits != increase the net risk
It took a while going through the data in the results section to see this.
Could.
I’m always kind of envious of the people who were able to lose weight on GLP-1 drugs. I lost a bunch of weight a few years ago, and still need to lose a lot more (430 lb -> 330, goal 240), but I fell out of the good habits for, well, no good reasons…
Decided to try Ozempic and was on it for about 6 months. Didn’t do a single thing for my appetite unfortunately, even on the max dose.
Sample size of one here, but if you’ve got mental health struggles that feed into your eating patterns, GLP-1s might not help with your weight problems.
Wegovy/Ozempic didn’t do anything for me for months. Then my doc put me on Tirzepatide+Phentermine combo and I forgot what being hungry even feels like.
Do you have to remind yourself to consume things like proteins, etc to prevent muscle loss?
I couldn't hit my macros on tirzepatide - couldn't get enough protein without feeling sick to my stomach. One of the reasons I swapped to reta.
(though as a general note for anyone reading, just getting enough protein isn't enough - you need muscle stimulus too. Getting enough protein will help reduce the amount lost but if you really want to stop it, you gotta do resistance training)
How long have you been on Phentermine? For me it stopped working after only a couple weeks.
It lets me more or less skip a meal but holy hell I am craving sugar more than ever. On the whole I'm cutting calories and have lost a lot of weight, I just wish I didn't want sugar this much.
I’ve always been more of a savory kind of person myself. I’d take biscuits and gravy or a steak over sweets any day!
But I feel you on sugar. Took me a long time to cut sugar cravings. A decade ago I cut regular soda out of my diet, which a few years later led to me cutting out pretty much anything sweetened. Realistically it wasn’t the sweetness for me, it was the “mouthfeel” or doing something with your mouth. Just straight sparkling water satisfied the entire craving for me.
The hardest thing for me to give up / heavily cut back on was fried things. Maybe that’s the result of my parents using french fries as the reward food when I was a kid…
Try allulose-sweetened stuff. Allulose is a sugar your body doesn't metabolize like sucrose. It has zero calories and does not increase your blood sugar. It's a component of maple syrup and so does taste a bit maple-y, but better than most artificial sweeteners and even stevia leaf extract (stevia and aspartame have a "tang" to them I dislike).
That's unfortunate! It might be worth checking out Tirzepatide or Retatrutide once it is released. The GIP and Glucagon receptors might be better targets for you, even if the GLP-1 receptor seems to not help.
Hey, I can identify. Sending good thoughts your way.
Try Fluoxetine 20mg, first 1 per day, later 2. Glp-1 doesn't work in stress related obesity.
I really had thought (with no research) the correlation between mental health and glp1 effectiveness went the other way around. Thank you for this check-your-biases moment, you probably just saved me a ton of embarrassment down the line, if these drugs ever enter my life.
So try Mounjaro. It works better.
You missed out on both of the weight suppression tricks, which really does suck. Appetite suppression (or reduction of food noise) is pretty useful, but GLP1s also tend to punish you mightily if you overeat. For me, even if I were hungry, overeating will make me hurt for hours. I could not gain weight on this even if I wanted to.
There are some difference, too, between the various drugs. I never tried ozempic, I went directly to tirzepatide (zepbound). And then to retatrutide. I will say that reta is in some ways the most interesting, because it has less appetite suppressing activity than tirzepatide (this is common, not just me), but it still cuts my stomach capacity quite a lot, and ramps up my metabolism. I had stalled at about 90 pounds down with tirzepatide, and reta immediately knocked off another 15. I track calories, and I had changed nothing. Felt more hungry, still lost more weight. Wild.
From one rando to another, I recommend trying tirzepatide. Or try semaglutide again but stacked with cagrilintide -- some people get pretty great results with that, similar to tirz.
Yeah I might just have to go get it out of plan. Kaiser covers Ozempic, but none of the Tirzepatide based medications. (Edit: looks like that might have changed)
I am a big guy (6’4, 330 lbs), but I was amazed that Ozempic just seemed to do nothing. I was having the gastric side effects, but I could still eat 3000 calories a day if I cheated without feeling anything.
I highly recommend Zepbound, you might try it.
Similar experience here with Tirzepatide. Overeating is punished swiftly and painfully.
If it works for you, look into getting one of the 15mg pens and counting clicks in order to get more doses per vial. I've been on the one pen for 3 months now and it's still got plenty of juice left.
One of the quirks of buying brand name GLP1s in the US is that we don't get the dial-a-dose pens, every autopen is one-shot. Some people disassemble them to get multiple doses, but at that point you might as well get the cheaper brand name vials or go with compound or gray.
When I was on Ozempic in the US (Bay Area), it was a dial-a-dose Ozempic branded pen. Came with 4-6 single use needles you’d screw onto the end before use, and discard into a sharps bin after.
Did you try those zero-sugar candy bars (often labeled as protein bars)? They work quite well for me, no messing with GLP-1 necessary.
Which do you like? Barebells salty peanut and chocolate dough over here. Though the sugar alcohols certainly aren’t great for you either, I think they were recently linked to stroke risk
Munk Pack is a good brand. They're like Kind bars but sweetened with allulose.
I went down from 390lbs to 240lbs gradually over 5 years. I have maintained a weight of 240lbs since then (6'1" tall).
The first year was the most dramatic loss of 100lbs. I was miserable and didn't know what I was doing other than counting calories. The rest of it was more considerate of total nutrition, and that's what made my good eating habits stick.
I say this because while I'm not a doctor I think GLP-1 is probably unnecessary for the vast majority of patients. Better food and information is more available than ever before.
I would strongly advise to watch your A1C and get out of the diabetes danger zone if you are. Most people can drop a few percent in as little as 6 months and it makes a massive difference in mental health. Blood glucose has a direct impact on the brain and overall cardiovascular health. If you drink alcohol, you might want to take a break also to let your liver/kidneys/pancreas do their jobs properly and restore insulin sensitivity and other hormones. Look into the "fruit paradox", and more generally get a good salad in for lunch to address nutrient deficiencies. Not crappy salads either. You're not a rabbit. Treat them like the amazing sandwiches without bread that they are.
Sounds like old advice, because it is, but I find people aren't listening because they want to more deeply understand why to do it and what the effects are. Convenience and unintuitive pricing are false bargains that get in the way of healthier habits. Focus on nutrition and not quantity. Change your groceries, change your life.
> I say this because while I'm not a doctor I think GLP-1 is probably unnecessary for the vast majority of patients.
We have mountains of evidence that willpower fails for something like 99% of everyone, which is far from a vast majority. I applaud anyone's efforts to become healthier, however (though 240 at 6'1" is still obese, I would still explore medicine if I could not get any lower "naturally").
Thanks for the reply. Your perspective framing this as "willpower" is precisely what I'm concerned about.
I didn't need any willpower to do this and I'm not even humblebragging nor think of myself as a tough guy. I'm saying that healthy habits are simply a matter of understanding. If someone wants to take GLP-1 on top of that, it's their call. Many seem to be under the impression it's so vital for their specific situation to lose weight or avoid a heart attack and I think that's plainly false. We shouldn't be feeding fear, and humans aren't that unique.
I did not change my diet. If anything I just added more variety with a specific intent and it worked. Even just changing the order in which one eats things (fiber before sugary foods) can make a big difference. Once I got the blood glucose under control all the strong cravings and eating mistakes basically went away on their own without my conscious effort. The body is all connected and driven by hormones.
> I'm saying that healthy habits are simply a matter of understanding.
Plenty of people have heard everything there is to hear on this, understand it, and still fail to implement it.
> I did not change my diet.
You plainly did. You do not lose weight without your diet changing.
> If anything I just added more variety with a specific intent and it worked.
This is changing your diet.
> Even just changing the order in which one eats things (fiber before sugary foods) can make a big difference
Changing your diet to eat more filling foods is a very frequently recommended thing, yes.
> Once I got the blood glucose under control all the strong cravings and eating mistakes basically went away on their own without my conscious effort.
My blood glucose has always been excellent. It did not stop me from having food noise and cravings.
Sorry, you're right. I meant that I did not make significant changes to my diet. My point was I didn't really change what I eat, but how I eat. I still hate certain vegetables like carrots, kale, brussel sprouts, etc. and just added more of the nutritionally equivalent and culinarily far superior vegetables I was already eating.
That's not willpower. That's looking things up in the USDA database and tweaking my existing recipes. Why force nasty carrots onto the plate when I can eat spinach, cantaloupe, pumpkin, sweet potato, etc.?
I guess I also didn't emphasize enough that I took things super slowly? Taking 5 years to do what I did is a really modest goal. I just wanted to manage risk with minimal change. This is the pareto principle in action.
If we're really going to argue over stats, the effects of GLP-1 is meaningless noise in comparison and probably way harder to commit to. I just wanted to eat good and not feel like shit all the time. Isn't that what everyone wants? What if instead of there being "one weird trick" or a "miracle drug", we consider that basic nutrition is simply misunderstood and full of hundreds of weird tricks that are proportionally much easier to implement and they're damn tasty too?
I'm not knocking anyone meeting their goals without GLP-1s. It's obviously possible in absolute terms - people have been making great body transformations for as long as we've had fat people.
But everything you did, plenty of people try to do and fail at it. You are making it sound like this is all it takes and that it's easy. It might have been for you! But it might not be for other people.
The fact of the matter is the overwhelming majority of people that are obese and go on GLP-1s have tried other interventions before and failed at them. ~70% of all obese people have tried to lose weight in general, ~50% have recurring attempts, and while I don't have stats to back it up I am confident that the sort of people who are willing to go and inject themselves every week are the sort of people that have tried to lose weight in other ways.
> probably way harder to commit to.
A subcutaneous injection once a week is nothing. Dealing with constant food noise? I could maintain that if the rest of my life was stress free, and that's how I would drop 30lb. Once stress came back? So did the weight. Because for me, rearranging food doesn't matter if I still can't stop thinking about it even if I'm not actually hungry.
I'm on reta. It does barely anything to suppress my appetite - physical hunger has never been my issue. And I can easily eat however much I want - most days I am below 2k calories, but Saturday was an annual event with friends and I'm sure between food and alcohol I was probably at 5k calories for the day. But what reta does, is absolutely murders my food noise. I don't think about food constantly. I don't go eat because I got bored. The only thing I have to commit to for it is, once a week, put a needle on my injector pen, twist the dial to the right dosage, poke it into a spot where I still have subcutaneous fat, depress the twist top. Once a month I reconstitute a new vial.
> A subcutaneous injection once a week is nothing
I do at least one a day, sometimes up to four if things happen to line up exactly right.
Even four subq injections amounting to around 2ml of stuff is nothing, doing all four of them after a shower takes about as long as brushing my teeth.
If you use correct technique and good quality needles, you will feel essentially nothing. If your needles are not sharp enough, there might be very slight discomfort when initially piercing the skin.
This is the study that the article references. (The linked one on the post is an older study)
https://bmjmedicine.bmj.com/content/5/1/e002150
The actual study states in the summary that it's the cardiac protective improvement that reverses, not that you're worse off for having taken a GLP-1.
So yeah, when you stop taking something that protects your heart and kidneys, it stops protecting... your heart and kidneys.
There's an increasing body of work that indicates that long-term GLP use (initially higher doses for weight loss, then tapering down) retains the cardiac and kidney benefits and can actually lead to additional weight loss.
Kind of makes sense that stopping taking a drug that reduces heart attack and stroke risk leads to a return to the higher risk of before.
It doesn't reduce heart attack and stroke. It reduces appetite, kind of, and gives you a sore stomach while making you shit yourself inside out. All this can, with care, help contribute to weight loss.
Weight loss can reduce heart attack and stroke, but GLP-1 does not.
You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often.
We see risk reduction for heart attack and stroke for people on GLP-1s even without weight loss, which belies the idea that the protection only comes from losing weight.
Edit: In fact, from the study -
BMI went from 35.86 (Continued) to 34.57 (Discontinued) to 35.48 (Interrupted),
Heart failure percentage was 11.57% for continued use, 12.73% for discontinued, 11.92% for interrupted
NICM went 3.10% for continued, 3.36% for discontinued, 3.31% for interrupted
BMI was higher for the continuing users and they still had lower heart failure and NICM rates than the discontinued and interrupted groups. (Also a bunch of other things including stroke and heart attack but I didn't want to write all of these out)
What is it about GLP1s that bring out the kooks who suddenly think diet and exercise are the only valid medical treatment? Is it a moral issue?
As best as I can tell, people are very attached to having achieved their body weight through whatever means they have determined are valid and derive self value from it, and believe that GLP-1s are cheating to achieve a result they worked harder for.
Yes, it's a moral issue.
What you need to understand is there are a lot of people where all they have is being skinny and appearing to be healthy. Without that, there's nothing left for them.
For a long time, there has been a moat that they can use as a justification for why they're better. They can say "well I work hard, I eat right, I put in effort!" The idea that others can achieve that without any of that means... well, they did it all for nothing. In their heads.
The dirty little secret? Many of them don't do any of that, it's just a delusion. Always has been. I'm skinny, you think I go to the gym? Fuck no! I should, but I don't. And I eat whatever I want.
But if a lot of people have to face the reality that their most redeeming quality is nothing of their doing, that would ruin them. Ruin them. They could just, like, get achievements or something but that's hard. Continuing the delusion is easy.
Unless we're talking about emergency care, most pharmaceuticals are completely unnecessary and carry serious risks.
There's not a single qualified doctor out there that would promote drugs before preventative measures.
Pretty much every adult fat person has attempted diet and exercise to resolve their weight issue.
Saying they should try this first at this point in the game is like having your support case escalated 5 times already and them saying "have you tried turning it off and on again"
Your comment is all kinds of wrong.
A) it does have cardio protective effects.
It does reduce your appetite, and for most people have very few side effects. If you get nausea you're titrating up too fast. Most people, because it slows gastric emptying, it doesn't make them shit themselves "inside and out". GLP1s are a decent option for treating ibs-d or bile acid issues and is better tolerated than your bile acid sequesterants.
> You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often.
This victim blaming advice has been given for decades and obesity rates have been climbing for decades. Only glp-1s have reduced that.
> You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often.
Oh wow it's so simple! why has nobody thought of this before??
You've been being told this your whole life.
You still think mass-marketed "low fat" foods are good for you.
You still think you can pop a pill to make your problems go away.
Isn't GLP-1 creating a "feel-good" starvation? Patching the receptors telling the brain one is not hungry and then just letting the body starve happily, leading to significant muscle loss and aged face? Contrary to e.g. water fast where the body switches to 100% ketosis that can run as long as there is any fat in the body and one supplements electrolytes (Mg/K/P/HCO3) and vitamins (predominantly B1/B2/B3), leading to a much more healthy appearance?
GLP1s do not themselves cause any worse muscle loss than you would experience if you lost the weight by watching calories the old fashioned way.
"Ozempic face" is almost certainly an artifact of people who spent their life significantly overweight having somewhat looser skin than they would if they had maintained a low weight throughout their life.
Also, not everyone gets the face effect, not by a long shot.
Not really, Ozempic face is the same face as one gets when starved of food for a longer period of time from low caloric diet that contains carbs. Ketosis on the other hand doesn't cause this unless one has almost no fat left as it doesn't switch body to the starvation mode.
There are two modes the human body operates normally - insulin-driven, active when carbs are in the food, and ketone-driven, active when there is a lot of fat storage and no food intake, or food has no carbs. Insulin-driven operation switches to starvation when food intake has caloric deficit but still enough carbs for insulin to be triggered; ketones on the other hand lead to zero insulin activity and pure fat burning; starvation is only activated when humans reach around 4% body fat while in ketosis.
This is a bunch of pseudoscience.
"Starvation mode" as people talk about it is generally nonsense - the exceedingly low bodyfat you mention for keto is the same place you would see it in a non-keto diet when we talk about actual starvation mode and not whatever you're talking about with a non-ketogenic diet.
The only real difference when it comes to the biology here is that fat mobilization into glucose is significantly slower and less efficient, which keeps your blood sugar levels more constant, which results in fewer post-meal food cravings. Which isn't nothing, but it's not muscle sparing in and of itself.
We have plenty of studies here. Keto diets are not better for sparing lbm.
https://pubmed.ncbi.nlm.nih.gov/38934469/
In fact, if you already have significant muscle mass, it might be worse. Glycogen is hugely important when doing resistance training, and keto significantly impacts your glycogen stores. People perform worse with their resistance training on keto than regular diets.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9244428/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8469041/
I suspect you have no idea that your body has two independent energetic circuits - one driven by insulin and glucose, the other driver by ketones. Just please dump this to any decent LLm to give you ELI5. Muscles obviously need glucose for their best performance which is why strength training is not recommended during ketosis; OTOH ketosis is naturally muscle-sparing.
> I suspect you have no idea that your body has two independent energetic circuits - one driven by insulin and glucose, the other driver by ketones.
I am fully aware - I have spent several years of my life following a ketogenic diet. None of that is relevant for "starvation mode" and insulin within that context. I was replying to your specific points - not providing an explanation on how ketosis works from end to end.
Unless you are claiming that your body just doesn't produce glucose/glycogen and insulin when in ketosis? Which would also be incorrect.
> Muscles obviously need glucose for their best performance which is why strength training is not recommended during ketosis;
Strength training should 100% still be done in ketosis/while following a ketogenic diet. It will be suboptimal compared to a regular training, but being in ketosis doesn't magically make resistance training optional if you want to be healthy.
> OTOH ketosis is naturally muscle-sparing.
It is not and the study links in my post show consistent data here. There might be an exception if you are an endurance athlete but that is based on far more limited data than the rest of the research. So... if you're a high level endurance athlete that is also somehow fat, keto might be a better option when it comes to sparing muscle, but for the rest of us, not the case.
Yeah exactly, what people call Ozempic Face is often just wrinkles. I look a bit older now that I lost 40 lbs, but much healthier shape. Fat does fill in your face some
Muscle loss is determined by your protein intake, muscle stimulus, and rate of weight loss. Plenty of people start lifting for the first time (or after having stopped for extended periods of time) when going on GLP-1s and actually put on muscle mass.
It might result in more loss of buccal fat than otherwise but even that is not definitive. Activating the receptors is not the same as burning fat - there are GLP-1 receptors all over your body in all sorts of organs. If you activate them in your brain you're not burning your brain for energy.
n=1, been lifting weights for 25 years and lost 40 lbs on Zepbound and counting.
I can still do my routines easily with no issues. My muscles look slightly smaller I think, but maybe that's the fat around them that's been diminished.
There is nothing inherent in your description that would support your implied claim about facial aging.
"Emerging research suggests GLP‑1 receptors are present on adipocytes and fibroblasts. Some animal studies indicate that GLP‑1 agonism may promote lipolysis in subcutaneous fat more aggressively than in visceral fat, leading to disproportionate loss of facial fat. It also may affect collagen synthesis or skin architecture, though human data are still evolving."
How much of this could attributed to simply having less artificial hormonal support for not overeating after discontinuing treatment, and falling back into old habits? I’d love to see more research focused on these mechanisms.
In veterans with T2 diabetes:
> To find out what happens when people stop taking GLP-1s, Al-Aly’s team of researchers tracked the health of more than 333,000 United States veterans with type 2 diabetes for three years.
Also News I guess - People who pick up smoking again after a period of cessation, regain all negative effects of smoking that they previously experienced during that past smoking periods, eliminating the positive effects of the smoking cessation.
Others have addressed the clickbait nature of the title
I'm just surprised the food industry or whoever is willing to fund FUD content that ostensibly has such an indirect effect on their bottom line.
Although I guess they spend a ton on ads which are also of dubious value, so maybe it's to be expected.
I mostly feel bad for job losses due to AI, but I won't shed a tear for journalists who make a living spreading misinformation about the results of research.
> They found that the risk of heart attack and stroke jumped in those that paused GLP-1 treatments for as little as six months, compared to those who continued taking the medication.
(Emphasis mine) The 'jumped' would more correctly say 'tended to revert to baseline' if you just had a basic LLM summarize this study for you...but then that wouldn't drive clicks and shares on your article.
Honestly don’t understand it. Feels like a lack of discipline. I was 250. Plugged in a bunch of numbers into an app and it gave me a calorie count per day. I brought a scale with me everywhere, used ChatGPT to guesstimate calories, I added 50% for good measure. A year later I’m 175. You can’t do this even with drugs you’re gonna get fat anyway.
I’m most curious about someone like me vs someone who lost the same amount on glp1 with respect to these stats
I'll bite!
A decade or so ago, when I was still in uni, I managed to get similar results naturally too - ~100kg down to ~65kg in around 18-24 months just by eating healthy and exercising more.
I put back all of that weight and then some during the COVID pandemic (I'm in Melbourne, Australia - we had the worst lockdowns on planet Earth) and this time struggled for years to lose it until trying GLP-1 drugs a few months back.
For me, what made it harder the second time around wasn't so much of a difference in discipline skills (if anything, they've improved) but the fact that there was so much more going on in my life - young family constantly getting sick, small business that started struggling, relationship/social issues, health issues (sleep apnoea) etc. etc.
I'd get on the weight loss train, lose a couple of kilos, then the whole family would get sick with the flu and I'd put it all back on again while recovering. Or maybe I'd be forced to shift my focus to the business so that we could keep the lights on. Or any number of things.
I guess my point is that it's not difficult to lose weight naturally (or any self-improvement, really) in and on itself, but it's completely different ballgame when you're fighting a war on 6 different fronts. Having one of those problems simply just disappear through GLP-1 drugs genuinely feels like a miracle.
We know that GLP1s have benefits that are disproportionate with just weight loss, so someone who is otherwise like you in terms of weight loss would probably have better cardiovascular markers.
Probably the biggest difference, though, is that an average "you" will be back at original weight, plus a little, in about a year, while the average GLP1 user will (assuming they keep taking it) be the same weight, or even a bit lighter.
Everything is discipline. If you just always do the thing you’re supposed to you will win at life. People can’t always do the thing they’re supposed to so they supplement with drugs that help them do it: caffeine, amphetamine, SSRIs, GLP-1RAs and related drugs.
In fact, everything is discipline. If you were disciplined enough to always put the basketball in the net from anywhere on the court you’d be Steph Curry. The thing is most people don’t have that kind of discipline. Someone runs up to them and puts their hand up in the air? They shoot wide or balk. Curry shoots true. Discipline.
Just always do the right thing and never do the wrong thing and you’ll be fine at literally everything.
Some things require talent like your examples, weight loss does not imho. The disparities in obesity and culture within country says it all.
Weight loss of course is helped by talent, because genetics are talent.
Metabolisms fluctuate, although granted not by much. But what really varies is your response to food. And it's not just genetics. It's food scarcity, early childhood, your environment.
The (maybe) sad reality is that there will be people skinnier than you will ever be who have put in zero effort. Nada. That's life. Just like there's people who can sing better than me off the rip and I took vocal lessons for 10 years. Life's not fair.
But the bright side is, I can drink and not be an alcoholic. Maybe they're just lazy or something. Or, maybe this mentality is one people feed themselves (ha) to feel better about the circumstances of their life.
Wouldn't we all like to believe we're the way we are because we're strong, brave, and hard-working?
The ability to be disciplined about eating is also a talent.
Or do you think that somehow genetics don't play one of the largest roles in your ability to be disciplined when it comes to food?
If you can be disciplined about taking a drug you can about food. How do you explain correlations in obesity across cultures? Genetic superiority? Again, imho just making excuses for laziness. The same logic you’re applying here also applies to even taking the drug and picking up refills from the mail…
Also look at obesity rates across time within the same country. It’s clearly not an issue of discipline, it’s an issue of what’s being eaten.
Why in the world do you think that taking a once a week injection requires even remotely similar levels of discipline to dealing with daily hunger and food noise? There's like, a dozen orders of magnitude in between. This is a silly argument.
> How do you explain correlations in obesity across cultures? Genetic superiority?
Every developed nation in the world except Japan has been seeing obesity and overweight rates rising at significant rates, including countries that have fairly similar cultures, such as Korea. You also see people move to America and stay in relatively isolated pockets of their culture and still gain weight.
So no. It's a matter of access to hyper palatable calorie dense food. The more of it around, the more likely people are to get fat. The fatter you get, the more of a feedback loop you end up in for a wide variety of known and relatively well understood mechanisms. GLP-1s help short circuit that feedback loop.
> It's a matter of access to hyper palatable calorie dense food. The more of it around, the more likely people are to get fat.
Now there’s something we agree on. If only we could agree that no one is stuffing cheeseburgers down people’s throat other than themselves. So close.
Once the shame around disgusting fattening food has reached a critical mass the problem will solve it self.
Ironically the excuses you make for them only worsen the issue. If fat people and the food they ate were appropriate shamed they both would cease.
FYI in Japan fat people are ruthlessly bullied. Fat people are rare. Food for thought, pun intended.
Stop tolerated junk.
> Now there’s something we agree on. If only we could agree that no one is stuffing cheeseburgers down people’s throat other than themselves. So close.
No one is saying that it is forced. What I am saying is that your sense of moral superiority for the fact you aren't is misplaced.
Let's give you an anecdote: Up until 18 or so, I was a stick. I went from being a stick to getting into powerlifting. I spent the first chunk of my 20s with a pretty great physique. Then as I had more and more responsibilities in life, I had less and less bandwidth to apply to things like cooking, exercise, etc. I slowly lost muscle mass. I slowly gained fat. I had never had food noise when I was skinny - I had never compulsively felt the need to eat, regardless of hunger. I had never had food just constantly occupy my brain. After my slow descent into obesity, something fundamental about my relationship with food had changed. When my stress was lower and I was skinny or later fit, staying that way was easy. It didn't require great mental fortitude, massive discipline, any of that. And when I got fat, it wasn't because I was craving food - it was because I had shit to do and couldn't take the time to cook. Or because I was going outwith friends or my SO and eating out was a huge part of my social life.
When I looked at myself and decided I had to change, I though I just needed to stop doing those things. Stop going out, force myself to take the time to cook and let other things fall on the backburner, etc. Except now I thought about and craved food in a way I never had before. I went from thinking exactly the same as you to realizing 'Oh shit. This wasn't as simple as I thought it was.'
I lost weight plenty of times. Significant weight - not just a few lb, but 30+. Multiple times. And then I'd get busy at work, I'd have family members going through problems and need help, I'd have a rough patch with an SO - as soon as my mental bandwidth got divided, the weight loss stopped and regain started.
Even if an individual is just always able to resist, it's almost entirely based on their genetics. If you want to feel superior because of something you had no control over, I guess that's your perogative.
> Once the shame around disgusting fattening food has reached a critical mass the problem will solve it self.
I think shame is a useful human emotion. We evolved it for a reason. But we also know that it has limits and that once those are reached more shame on top, it becomes counter productive.
> Ironically the excuses you make for them only worsen the issue. If fat people and the food they ate were appropriate shamed they both would cease.
No. Fat people experience plenty of shame, and for a huge amount of them, it only worsens the problem. Once you shame a person too much - once you make it about them and not about the action - they start to feel that they are unable to make a change because they have less worth than those people that can, and often end up losing even more control in their relationship with food or whatever else they are being shamed about.
> FYI in Japan fat people are ruthlessly bullied. Fat people are rare. Food for thought, pun intended.
This is not universally true - it is highly regional, though the most populated portion of Japan is definitely an area where this is largely the case. But even in areas where this is not the case, they still have significantly lower obesity rates. Osaka and Hokkaido are significantly more laid back about it than the Tokyo area, for example, but they still have relatively flat obesity rates.
Basically every fat person in the developed world receives more than the maximum effective dose of shame over their body and it hasn't made them stop being fat.
You just have to be disciplined to always shoot accurately at the basket. Most people send it one way or the other but if you are disciplined enough in your aim at the basket no matter the constraints you will be the best basketballer of all time.
This makes it even more fantastic that the supply of GLP1s from my country's only legal importer is spotty and I've been suddenly cut off twice already
One benefit of going gray is that you can stock up. If I could not get any more, it would be a number of years before I ran out.
Studies get worse every year.
Or articles that try to convey the content of studies have always been poor and continue to be poor.
The most capitalistic drug ever! Take the drug forever and lose weight but stop taking it and you’ll die.
That isn’t what this says at all.
(off-topic, but since the thread already is..)
HN felt like one of the last places on the internet I could have good-faith conversations with intelligent people who would form thoughtful, on-topic replies.
And now it feels like the user base here has shifted enough that the voting system no longer consistently elevates the interesting comments, but the comments that reinforce people's worldviews.
Everyone feels Eternal September sooner or later. I recommend blocking users on this site. Having hit about 800 or so blocks I find that the conversation quality has skyrocketed. You still get one or two low quality users on a thread like this (I hadn’t blocked this guy) but the truth is that it’s usually a few people.
Any time a user gives me a flash of annoyance with a nonsensical comment that’s the last time I see them. This isn’t a native feature but Claude will implement it for you in a really short amount of time. If you want a feature set to copy or a list of users to seed, you can just copy mine (in profile).
Yeah, unfortunate that it's come to that, but I think you're right.
I started to write a comment about having some (additional) ideas for a Chrome extension, clicked your profile, watched the YouTube video. Fantastic. I think it already does everything I wanted.
Thank you for making and open sourcing this!
Everyone feels this way about HN at some point, it is normal. It is probably true that the user base has grown and so you see more low-value comments in absolute numbers as time goes on, but I still think the overall quality is decent and the community moderation solid.
It is also a Friday afternoon, and HN's weekend (and to some extent overnight) 'personality' is noticeably different than during typical business hours. I enjoy coming here on weekends but it gets a bit more wacky.
What do you mean? All of the comments that misunderstand the study are downvoted from what I see.
We finally found the first morbidity signal of GLP-1s (or lack thereof).
These are life changing drugs, but like plastic we'll see their effects in force within this generation:
> The longer time spent off GLP-1s, the greater the risk of major cardiovascular events—up to 22 percent for those who abstained for two years.
Doesn't it make sense that, if you were taking a drug that reduces morbidity, you'll get increased morbidity if you stop it?
Not if having a heart attack within 1 year at a higher rate is an co-morbidity factor when the primary treatment was for obesity or diabetes (not stating that obesity and heart disease are not positively correlated).
To use a dense analogy: if I stopped brushing my teeth I would not expect to die of gum disease.
I don't think you read the study. The people returned to their pre treatment risk profile after ceasing treatment
You are misunderstanding the study (largely because the article heavily misrepresents it, would be my guess)
They do not see an increase against their pre-GLP1 baseline risk - they see a reversal of the cardioprotective benefits the drug provided while they were on it.
You failed to understand the results of the study and quoted a passage that does not in any way support your assertion.