I’ve been on Mounjaro since August. Down almost 60lbs, and it’s been a life changer. Have I had some gastrointestinal issues, sure, but expected. I feel great and my brain seems to be functioning as well as when I was in my 20’s. Now, when I go to the bar with friends, I end up having maybe 2 beers and although enjoyable, I don’t feel that light switch turning on which encourages me to drink more. Can I force myself to keep drinking, say if my good friends are in town and we’re going out all night? Sure, but there’s some reward center that’s no longer lighting up. I just get drunker, but it’s not more pleasurable. I was never a big drinker at home by myself. Maybe a glass of wine or two with dinner if my in-laws are coming over. Now I’ve literally had zero drinks at home by myself. Seems to have started changing about 3 month in.
Work also seems more interesting, but my untreated ADHD seems to be getting worse.
>I feel great and my brain seems to be functioning as well as when I was in my 20’s
>but my untreated ADHD seems to be getting worse.
I had very similar results after taking ketamine for treatment-resistant depression. It eliminated all my compulsive tendencies for getting cheap dopamine hits (food, doomscrolling, etc), reset my tolerance to everything (caffeine, ADHD meds, alcohol), and made my ADHD worse while improving throughput and ability to Get Shit Done.
I wonder if they affect the same parts of the brain in a roundabout way? Ketamine is also used to treat addiction (opioids, primarily).
Do you experience any anhedonia while using Mounjaro? Did your overall pleasure response get blunted?
Ketamine treatments help people, because ketamine is a dissociative drug. It makes you not feel your suffering, also makes you not feel the positive feelings. That’s why you’re not eg doomscrolling. It doesn’t feel good for you anymore.
If you’re not getting treatments regularly, you will be back to suffering in a few months likely.
In my opinion, there are better alternatives and more effective treatments than living a life of disassociation.
This isn't true. I am not dissociated when not actively undergoing the treatment.
If anything, the after-effects of ketamine treatment alleviate my lifelong dissociation and other symptoms depression and PTSD. Something about the induced dissociation "wraps around" and snaps people back into fully being present.
Have you ever had ketamine treatment? Where are you getting these conclusions?
Yes I did have two treatments. After the first treatment I really liked it and I thought I had my life back. All my debilitating symptoms were gone. Weeks after the second treatment I noticed that my depression and trauma is not gone. It just made me not constantly aware of it, if that makes sense. I was not clinically dissociated as well, just dissociated from the things that caused my suffering. I didn’t think that was a healthy way of living, so I stopped getting treatments.
Luckily I found forms of treatments to actually heal after that. I’m incredibly glad I did.
Ketamine didn’t heal me, my perspective just changed, which can be valuable though.
> Weeks after the second treatment ... I stopped getting treatments
This sounds like an unusual, very sparse schedule. Most ketamine treatment routines have many more than two doses, and nothing resembling multi-week intervals between doses at the start.
My wife has undergone ketamine treatment, and as part of it, I read up on the literature. Typical ramp-up schedules (like hers was) would be one or twice per week for one or two months, and then less frequently until you stop or go into "as-needed" maintenance dosing.
I'm glad you found other things that worked for you, but what you describe doesn't sound like a normal course of ketamine treatment.
I don’t know it might be. I went in with the mindset of wanting it to help me end my suffering, not change my perspective. I think that’s the case for most people.
Your perspective is the suffering though, unless I am missing something? The whole thing with trauma response and all the various things that come from that is that different things have different effects on different people, because their perspectives are different. The treatments that work (CBT, EMDR, etc) also rely on changing your perspective of the event or your response to it.
this is not true at all. the dissociative effects only last a few hours. the clinical benefit is because ketamine stimulates neurogenesis in the mPFC and hippocampus, restoring plasticity lost in depressed patients.
Yes the immediate effects last for a few hours. I didn’t say otherwise. The current scientific literature paints a mixed picture of ketamine. While it can stimulate neurogenesis, there is a definite potential for neurotoxicity. Not to mention that there are no long term studies out there.
There are countless people reporting being anhedonic after treatments.
Only a few people have been reported to not relapse before 24 weeks.
I’m not making unsubstantiated claims. Don’t accuse me of that, because you don’t like my answer.
unclear. on the onehand, unpublished studies in gorillas show no lesions. on the other, retroactive studies of heavy polydrug abusers show lesions. not super high-quality evidence either way. there's also rat studies showing lesions, but rats are unusually sensitive to neurotoxicity from dissociatives. they get similar lesions from nitrous oxide while humans get no such thing. honestly the potential bladder toxicity is more concerning imo.
>relapse rate
still much better success rates than SSRIs.
not saying ketamine is perfect --- would be better to have a purpose-built drug, and a lot of the clinics are kind of scummy and charge exorbitant prices. but this + non-psychedelic 5ht2a plastinogens are the most promising things to come out of depression research in the past 45 years.
We don't know of any cure for depression, but with ketamine we have an effective rapid treatment.
Ketamine has a great therapeutic range, a well-understood side effect profile, and can bring a patient back from the brink of suicide in a matter of hours. It's also incredibly inexpensive to produce, on par with aspirin. Why shouldn't we use it?
That’s the thing. We don’t know a cure, but we know of people who were cured. We just don’t really know how or why, scientifically speaking.
And as far as I know there was never someone getting cured from t1 diabetes.
That’s what I meant by apples and oranges.
Ketamine or suffering & death? Ketamine no question. I agree, but it’s not so black and white how you may perceive it. It might be ketamine or death for you, I don’t know. For me it was certainly. So sorry, if it is for you now. I’m not telling you it’s bad or that you shouldn’t do it. Do whatever you think is the best for you.
I went through all of that and found other methods of treatment actually effective of solving the root causes of my suffering and not just the symptoms.
Meditation, somatic experiencing and mdma therapy[1] are the main methods I found the most effective, in no particular order.
I’m not looking to argue about your choice of treatment. If you want to share your experience or hear mine, give me a way to contact you.
Have a good night/day.
[1]https://www.nature.com/articles/s41591-021-01336-3
your link is for PTSD, not depression. no studies have come out so far showing MDMA has any effectiveness in depression. the proposed mechanism for PTSD involves serotonin release leading to heightened extinction of fear memory in the hippocampus and amygdala. no reason to believe necessarily this will help with depression.
I started taking it in November and I’m down 30 pounds and my retina has detached 2x for no apparent reason since then. My drinking is unchanged, except I get full sooner and drink slower. Because of the discomfort.
Oh my, is retinal detachment a known potential side effect of the drug? Or is that a complication of diabetic retinopathy or some other condition that you already had? This sounds frightening. Hope they were able to reattach it, and hope you're doing alright.
I can’t find the specific study this website cites, but it mentions:
> In a 2-year trial among patients with type 2 diabetes and high cardiovascular risk, patients treated with this drug experienced a great incidence of diabetic retinopathy complications (3% vs 1.8%). The absolute risk was greater in patients with a history of diabetic retinopathy at baseline (8.2%[drug] vs 5.2%[placebo]) than those without (0.7%[drug] vs 0.4%[placebo]).
Non diabetic, didn’t/don’t have diabetic retinopathy. I had assumed that the detachments were unrelated to Semaglutide but just happened as a freak coincidence in time.
The no apparent reason was a bit of hyperbole, since my vitreous was pulling away from the retina and brought some pieces with it during the process. But as to why that was happening at my current age is unknown. Second was likely related to stress in the eye from healing from the first surgery. But the point was I didn’t take any blows to the head or eye, or any other common cause of retinal detachments.
This was covered in a recent YouTube video I saw on semaglutide treatment. The real problem is rapid changes in your blood glucose levels can radically change your eyesight, regardless of the cause. So, with Semaglutide and other drugs, you need to have a slow ramp-up period and let your body get adjusted to the drug, otherwise you risk having those rapid changes to your blood glucose levels.
Thanks, I am stable for now. There is some vision loss but only in the periphery, my most recent surgery was on Tuesday so it’s not clear how much is permanently lost and how much will continue to return as the eye heals.
Good job, nice to see it works on reducing alcohol consumption too. I do not need this drug but it's nice knowing the option exists it need be. It gives hope to others too.
Obese people can actually be pretty muscular in my experience, due to their need to heft around their size. It's their endurance that isn't there since their hearts are quite weak.
It still won't get you to the 2/3 point making sense. If someone is 250 lbs and 35% BF and they lost 50 lbs, 2/3 of which was lean, they'd end up 200 lbs and 35.5% BF. That's possible, but I don't know if anyone would be recommending it at that point.
Peter Attia made a video recently using precisely that observation as the reason he avoids prescribing it except as a last resort, and only then when he can get patients to increase their protein intake and start strength training while getting a DEXA before and after to keep track of the relative changes in body fat percentage.
The problem is apparently that studies only use change in weight instead of body composition, so doctors have to be aware of that and get the patient measured themselves to make sure they're actually getting leaner instead of losing weight but getting "more obese".
> The problem is apparently that studies only use change in weight instead of body composition
Misinformation. Many of the studies track total fat, lean body mass, visceral fat, and literally dozens of other secondary outcomes/endpoints. See an example of such results here: https://clinicaltrials.gov/ct2/show/results/NCT03548935
This has already been covered yesterday in sibling comments about the NCT03548935 study and Peter Attia being in general a source of misinformation.
this is likely incorrect because people are confusing lean body weight loss for muscle loss. lean body weight loss does not mean only muscle loss. lean weight includes non muscle like skin, organs, etc.
This is true but it's still extremely well established that you lose some muscle along with fat if you're in a prolonged caloric deficit without sufficient protein and strength training.
If you're interested - not pushing an agenda. Here's what worked for this weird dude to not drink and stay fit.
I used to lift and be real fit till about 40. Like bulky-lean looking, bench 400 10x with a 6pack. Had a lot to do with being on the road for work all over the world, and you sit at the gym at the hotel for an hour every night because of nothing else to do, and there are girls there also on business who you'll never see again. I drank A Lot, ate anything I wanted, and did lots of blo on weekends.
It was getting out of control, so I did months of google-foo, went to a pharmacy in eastern europe, got like a thousand 150mg disulfiram pills under the counter for fifty bucks, and took one pill every morning for 2 years. You don't drink, you can't drink or you die, you forget drinking exists and after a couple of months don't even think about it, yet still do all the same stuff you used to - like dancing and clubs if that's your thing. And it's even more fun. There were no side effects.
Then things changed with age, testosterone went to crap, joints hurt. I got married and settled down. Can't work out too much now - just a couple of hours per week, and no heavy weights. Within 2 years I couldn't fit into my clothes and had high blood pressure and high cholesterol.
I realized I don't eat because I'm hungry, but because it keeps away sadness. So I changed my diet so I could eat however much I want. I now have a 4-pack instead of 6, fit into my pants, and eat however much I want.
I cut out fat completely. No oil when I cook besides a light spray on the frying pan. No nuts. Tuna - not salmon. Real expensive lean filet if I want cow in my mouth. Only white meat from birds. All the pasta, rice, and potatoes I want, but zero sugar added to anything. Lots of splenda and sweet n low. Fat free fairlife milk (lactose filtered out = less sugar calories). I eat normal sized meals.
Then, I have fruit and berries, and I eat as much of that as I want. I'm stuffing my face the whole day. Today, I had a pint of blueberries, 5 medium apples, 2 mangoes, and a pound of grapes.
Speaking of gastrointestinal issues, my poo is now soft and gentle, and smells delicious.
This is such a "one weird trick your doctor doesn't want you to know!" anecdote. Mounjaro and Ozempic are generally prescribed in instances where dietary interventions are insufficient and perhaps one of the last resorts before bariatric surgery. If your dietary interventions worked for you -- great! But there is only a certain class of people for which they work for, and it is rude to assume the OP hasn't tried these methods already (it would be surprising if they hadn't, since so many people can't help themselves from offering this kind of advice unsolicited).
With regards to cutting out fat, if you are advocating for a weight management plan for the general person, it is really too prescriptive and doesn't take into account that someone following your diet should not be accidentally increasing your carbohydrate intake (fruit sugars are still sugars!), resulting in the diet being a total wash. The gold standard for diet-based weight management is food journaling, and not cutting out an entire group of macronutrients without holistic consideration of your diet.
I was slightly overweight, 22% body fat 6’2” 220, and was suggested semaglutide (generic ozempic) all other standard health metrics in the healthy range. It’s not some crazy last resort drug, it’s basically everywhere and readily available to anyone that want it.
I’m 6’1”, and my goal weight is 210. In theory I should get down to 180, but expect I’d be too skinny. Currently 246, so I have 6-8 months for my personal goal, and at $1200/month, I may self fund for the remaining 3-4 months to hit that goal. Not sure if I’m willing to drop another $6k to hit 180lbs.
and... this person now takes these last-measure pills forever? or here in the real world, do they use the pills to lose weight, and then maintain that normal weight forever with... perhaps a diet trick that works?
people who have to take last-measure medication usually don't stop eating when they are full. i know, it's weird to tell someone who doesn't stop eating when they're full, how to still maintain weight if they... don't stop eating when they're full. i'm a weird guy with ADD and get side-tracked easily. I got an appointment with the florist about that next week, hopefully he can recommend a medication.
yes, a doctor will not tell you diet tricks. if you are asking your doctor for diet tricks, we need to step back a minute. when you're done grocery shopping at jiffy lube, drive home, sit down, and carefully read this link.
Obesity is often a chronic medical condition that’s not solely controllable by willpower. There is no difference between taking pills for treating obesity as a chronic condition vs any other chronic condition, like type 1 diabetes. Decades of treating obesity as a personal failing have resulted in worse and unsustainable health outcomes.
And again, you are being far too presumptuous about OP’s interventions. And I certainly don’t know what this business about ADD appointments at the florist or grocery shopping at Jiffy Lube you’re talking about is.
I suspect a chat bot, maybe not got-4, but maybe Bard? It’s close, but there was no point and the references were off but weirdly close. Like florist could be psychiatrist.
I suspect someone who lacks social interaction in life, so does not understand subtle satire. Like a problem that could be solved by a florist. By talking to the florist, making friends with the florist, and having some bbq outings with the florist and her friends on the weekends.
but before one would do that, which may be an insurmountable long-term goal, someone should compare going to a florist for pills, to going to a doctor for making up diets.
so, would you say a solution to the problem that lets you eat as much as you want, so you don't have to use your willpower, be an appropriate solution to suggest? There is a difference between taking last-resort medication for the rest of your life, and eating apples.
Substantial weight loss is possible across a range of treatment modalities, but long-term sustenance of lost weight is much more challenging, and weight regain is typical1–3. In a meta-analysis of 29 long-term weight loss studies, more than half of the lost weight was regained within two years, and by five years more than 80% of lost weight was regained (Figure 1)4. Indeed, previous failed attempts at achieving durable weight loss may have contributed to the recent decrease in the percentage of people with obesity who are trying to lose weight5 and many now believe that weight loss is a futile endeavor6.
Again, great that your regimen works for you! But a lot of these purely behavioral interventions are really not sufficient.
where in the world from what I wrote, did you get the idea that I was saying the obesity in all cases can be treated by eating as many apples as one likes. I also don't remember saying that apples are sufficient. I'm not taking your word, but you should take my words. Take my words with your eyes, have the brain process my words, and respond to my words and only my words. If you hear other words that your eyes do not see, don't respond to those.
People like you are the absolute worst to deal with when struggling to lose weight. I managed to lose 150lbs, and it had very little to do with will power, at least the way people like you mean it.
I had to reconfigure my entire life around it. I kept barely enough food in the house to meet my calorie target for the week. I once fell asleep while driving home from work and ran off the road because my blood sugar was so low. I spent 9 hours a week doing intense exercise and pretty much any time I wasn't doing that or working I was just sleeping. I basically had to have no social life, because socialization around here pretty much mandates large quantities of food.
Is something physically wrong with me? Probably, but good luck getting an American doctor to give a flying fuck. My thyroid stopped working when I was a child and it went undiagnosed for two years because doctors just keep telling my mother I was lazy. Ultimately a toll booth attendant diagnosed it because her dog had similar symptoms and my mother had to go full Karen to get the simple blood test to happen. American physicians are fucking useless.
Even treated, to this day I have to eat well under the caloric requirement that I "should" be eating and constantly feel like shit in order to lose weight, which makes me perform worse at work and apparently require 3-4 hours extra sleep every day.
I can guarantee you "willpower" people aren't doing that. Your body isn't fucked up and constantly demanding more calories than you need, so it comes easy to you and you probably just take any excuse to feel like you are better than other people.
I don't know how you can take a response that says "don't fight the willpower war, just give in and adjust your life so you don't need willpower" and interpret that as the polar opposite of what was written.
It is people like you who are the absolute worst to deal with. You take a specific example which probably does not not apply to your body, completely and completely twisted what was said so you can both be a victim and feel superior.
I specifically stated a diet that for a person who is working out a couple of hours per week, there is a way to constantly eat and minimize the caloric intake despite large amounts of food. I did not remotely suggest stuffing your face all day is a willpower-based solution to a thyroid problem.
I'm 5'11. In my early 30s, I was a 31 waist, 170lb, benched a full set of 400lb, ran cross country, and had 6% body fat. In my late 30s, I was a 34 waist with high blood pressure. I made the change in my diet, and a few years later, I'm a 31 waist, 170lb, normal blood pressure, and 10% bodyfat, and I eat as much as I feel like, just not whatever I feel like.
This is a solution for maintaining a healthy weight in an active lifestyle, that uses zero willpower, because my willpower is bad. This is not a solution for someone with a thyroid problem who needs to lose almost the weight of my whole body.
I don't know what it is with you and this other guy. You read very simple basic text, and you reply to something you've completely made up. It's like your brain paints a virtual world for yourself where you can feel constantly offended. No one's out to get you. No one's making fun of you. People are talking about something that clearly wasn't for you, so you inject yourself into the conversation so you can feel attacked. Stop that.
> In my early 30s, I was a 31 waist, 170lb, benched a full set of 400lb, ran cross country, and had 6% body fat.
> In my late 30s, I was a 34 waist with high blood pressure.
> I made the change in my diet, and a few years later, I'm a 31 waist, 170lb, normal blood pressure, and 10% bodyfat.
Your enormous transformation was gaining and losing 3 inches on your waist over the course of a decade or so? WOW! Thank you so much for taking the time to share your perspective. That's incredible. Honestly it's amazing to be inspired by someone like you who has been able to manifest such a huge change from exertion of willpower alone. Reminds me of this video: https://www.youtube.com/watch?v=lsSC2vx7zFQ Let me know what you think about it!
They talk about how if you want success, you need to treat it like the air you breathe, that once you want something as bad as you want to breathe, then you'll finally get there.
Huge respect for your personal transformation, and the insane willpower you channeled to lose 3 inches of your waistline over the course of a few years. Being able to drop one whole pant size is simply incredible.
I’m hopeful that it’s more like 3 months out of the year. Looking back over the years, I’ve gained roughly 5lbs/year since I hit 30. Now in my late 40’s, during Covid, it seems like that went to 10lbs/year.
The first 3 months on mounjaro, I lost 20lbs, so that cycle should be sufficient. I’d stay on it permanently, if it weren’t for the $1200/month.
Here's something I tried that's a 5-year max type of solution. If my suggestion for "stuff your face with fruit" isn't for you, maybe this is. If you absolutely Have to eat fatty foods, there's Alli. It clumps about 1/4 of your fat intake into large balls, so you poo it out. For small weight gain like yours, perhaps it's enough reduction to maintain current weight. You can't take it longer than a few years, because you'll have vitamin issues. Oil-soluble vitamins dissolve in the clumped fat and don't get absorbed.
I tried this a few years before going with my "apple diet." It works, but my bloodwork after a few years said I need to stop. There is a catch. The first year, you Cannot pass gas. That clumped oil that comes out, comes out very easily, and unfortunately Alli makes you gassy too. This side-effect goes away in about a year if you power through it.
Not a dietician or a doctor, but perhaps your mounjaro treatment can be cycled with Alli (cheap, OTC) every few years to save some cash. Invest in a large bottle of Dawn dishsoap. Put it in a spray bottle and spray the bowl after you do your stuff. You'll have to, just trust me.
What's your bloodwork and cardio like now and what does your doctor say? No fat + high carbs flies in the face of everything I've read that was published in the last 20 years. Maybe you've found another path to health?
I believe there's a fair bit of evidence to the effect of, any "diet" that restricts one's food options - be it calorie restriction, low fat, low carbs, low protein, intermittent fasting, no sugar, whatever - will result in weight loss as long as it's stuck to. Which makes sense logically; if normally you'd eat whatever you felt like, and then you restrict what (or when) you're "allowed" to eat, some substitution will be done, but you'll likely also just eat less.
And then when you go off the diet (either intentionally, or more likely, by just slowly drifting back to the norm), you'll return to eating what you were before, and will return to your original weight. Which is why the only diet that works is one you can stick to indefinitely. So, if the parent can stick to a no fat, high complex carbs diet for life, it will probably work for them.
I’ve been a fan of the keto diet (low carb high fat) for a while. But I suspect any diet that cuts a very large group of foods like carbs or fats out forces you to be more mindful of what you’re eating. And that’s a large part of the weight loss on those diets.
Elsewhere in this thread it was stated that food journaling was the gold standard in weight loss, which also I’d expect to increase mindfulness around eating.
What are you talking about? Wholegrain pasta has like 40g carbohydrate that includes 1g sugar. Brown rice has around 25g carbohydrates that includes 0.4g sugar.
After 2 years, my blood pressure went back down to a steady 110/75, heart rate about 55-60, bad cholesterol is on the low of normal range. I do about 2 hours of cardio with light weights per week, no longer lift. That's not a lot, but it's enough to stay at the same blood pressure for many years now.
I don't do high carbs - fruit are not high in carbs you actually process. I eat normal portions of complex carbs like bread and pasta, normal sized meals. I eat a ridiculous amount of fruit, and that has some sugar in it, but it's actually not that much. What that does is increase my fiber intake to ridiculous levels - and that has many benefits.
My issue was that I use food as an anti-depressant, and to deal with stress. The solution had to involve eating a lot, but minimizing calories. That's why the fat had to go - I can eat twice as many carbs as fat for the same weight. When you look at things like fruit - a lot of those "carb" calories you don't even metabolize since it's fiber.
I don't think I have discovered some magical solution, but it works for people like myself, who have what I consider a minor mental illness called 'self-medication with food.' Mental problems are a lot harder to fix than just not using oil and replacing nuts and chips with fruit. My solution to win the war was not to fight it and learn to live w/ the fact that I'm not perfect, and adjust the lifestyle to that.
High carb diets are a bad idea. I eat normal balanced meals, just with no fat. Long-term high fat diets are for people who want liver damage, and stop eating when they're full. A little bit of fat makes you full, unlike carbs. But keto is terrible for your health if you do it for decades.
The tiny amount of fat I do get, is from things like red tuna and other low-fat fish. It's amazing how little good fat you actually need in your diet, if you look that up. Literally one can of chunk light canned tuna is all you need for the day.
Now here's something groundbreaking that's pretty good - thin and wide no sugar no fat pancakes:
1 cup flour, 3/4 cup fat free fairlife milk, 2 packets splenda, 1/2 cup Egg Beaters. mix real well so it's runny with no flour chunks. no need for baking powder. real short spray of oil to just get some drops on a teflon pan. no need to spray when you flip.
Now my diet is not high carbs, but let's address the "no fat+high carbs = bad." the reason that's everything you've read in the last 20 years, is because that's what you chose to read. there are different diets for different causes of fatness in people.
fat makes you full faster so helps you eat less calories. carbs make you work out harder, so you burn more calories. if you have an active lifestyle - carbs and no fat. if you sit on the couch after sitting at the office, you want fat and no carbs. dietary fiber isn't something you should count as carbs.
if the reason you're overweight is because you like to constantly eat, and it has zero to do with hunger - you don't want any fat. you want the most amount of food for the least calories, and fat is double of carbs per gram. you want lots of indigestible fiber a normal amount of carbs, and eating the potatoes with that thick rough skin, with the skin.
Not at all, the two events are clearly separate in my account of history, and are actually about a decade apart. The weight gain, as with 99% of people, comes from a testosterone change once you approach 40yo.
It's really strange how you and a few other people just keep making up weird scenarios, then attacking those to make yourself feel superior. I don't get it. It was 1/4 book page of simple text. How is it possible to read something that simple, that short, and then make up something completely different in your head. This explains a lot of politics, but I don't get what people with that mental illness are on HN. Please stop. You are not superior - you have reading comprehension problems.
This is kind of weird because there’s a lot more data to suggest now that dietary fats are almost never the problem when it comes to obesity, and in fact dietary fats are really important for a lot of critical processes (brain function, neuroprotection, hormone synthesis). I get it for caloric restriction though since fat is denser than protein or carbs.
the most surprising thing to me is how you’re describing normal behavior that I can relate to all my life, but the community of strugglers is so big that this is a whole testimonial people feel comfortable and exalted to share
like thats not something I’m deriding its just news to me
makes me wonder what this drug actually does, flush gut bacteria? just the right ones?
For a long time we have known the existence of a network of hormones controlling our apetite on the gut brain axis, with names like ghrelin, leptin, glp-1, orexin, somatostatin, list goes on [1]. Issue was the network was tres complicé and hard to perturb without getting the opposite effect than what we wanted. Finally with glp-1, sglt2 and pcsk9 inhibition we are starting to be able to correct in the right way.
To answer your question, yeah turns out it was never about will power. Some people just had hormone drive to be healthier than others and finally we can pharmacologically start to level the field.
People talk about willpower but they ignore social influences like children learning habits from their parents or simply being forced by their parents to become obese (all it takes is a portion size that is slightly too big and demanding that you eat the full plate). No amount of willpower is going to end that unless you want to blame children for not running away from home.
> People talk about willpower but they ignore social influences like children learning habits from their parents or simply being forced by their parents to become obese
As a very young child, my family was probably on the upper end of poor. "Treats" were rare and food was not anything to be wasted at all. I'm almost 50 now, and it's virtually impossible for me to throw away food. I have to have an inner monologue conversation with myself about whether I really need to finish my portion and whether it's OK to discard it. Needless to say, despite being very physically active, my weight has challenged me my entire life.
As a parent, I'm irrationally proud of my child for being able to stop eating when they're full, even if it's ice cream or a treat. That's actually helped me get over throwing food away (a little bit, at least)
Find the right exercise/workout for you and it'll be its own reward.
Shouldn't take more than a bit of caffeine to get you moving at that point.
As to empath mode, you've just described MDMA. But it'd be nice if there were something a little less intense. That you could take weekly without frying your brain & was mild enough for family/work social situations. (And no, alcohol doesn't fit the bill).
The pleasure of working out only becomes obvious after you've built the habit to do so. You'll know you've built the habit when it starts to feel bad when you don't work out on a day you're normally supposed to. It's pretty similar to a drug addiction.
I've been doing calisthenics 3 times a week since 2019. When I skip a day I feel enormous amount of guilt and I can't sleep when the night comes. Still, I don't like every moment of doing the exercises and I have a feeling of time being wasted by tending to my body instead of doing something with my family, cooking for them or being creative. What's more doing the workout eats a huge amount of my will power and leaves me unwilling to do any other chore for that day.
That's not so easy, but also not as hard as you think. Won't take a lot of time on any one thing to see if it clicks for you. Pick a couple of activities, do each from absolute beginner level, twice a week for four weeks. Once if you're pushed for time. Keep the one that sucks less after a month. You don't need to hear the voice of God to download the Couch to 5K running app, grab a basic weights set and watch a few vids on simple exercises, or sign up for a local yoga or spin session.
The high can be way better than you'd believe possible before you try. Or if you don't believe personal anecdote.. /something/ must be keeping all those people coming back to it at considerable expense, hassle and time.
Do you want to live in the world of we happy few? This is what you’re suggesting with your rose colored glasses. What would really happen is companies would get the drug legalized so they can pump into their employees.
Any effects on gut bacteria will be very downstream of its primary effects, which are on:
- GLP-1 (semaglutide)
- optionally, that and also GIP (tirzepatide)
- optionally, both of those and also glucagon receptor (retatrutide)
But these hormones directly make you not hungry, among other things. They are probably some of the things that your gut bacteria manipulate to commandeer your behavior.
I’m glad people are enjoying Ozempic. My experience from seeing a family member on it, is I would not touch it if I were a 500-pound alcoholic smoking two packs of cigarettes a day. That’s an exaggeration since it probably outweighs the health issues there, but only slightly.
The person I know taking Ozempic has only lost weight (35 lbs) due to the fact that eating now makes her sick. She has been sapped of all energy and has developed issues with her bladder, circulatory system, joints, thyroid, and digestive system since starting Ozempic. I’m not saying it’s due to Ozempic, but I am saying all these issues have cropped up in the few months since she started taking it, and she never had any chronic health issues prior. At least she lost some weight, I guess.
As a counter-counter-point I've read most (~90%) of the papers that come out of trials registered at http://clinicaltrials.gov/ for all GLP-1 agonists, including ones that haven't been approved. The vast, vast, vast majority of secondary outcomes, for things like
- blood pressure
- lipids (HDL, LDL)
- insulin sensitivity
- blood glucose
- strokes
- cardiovascular events + deaths
- myocardial infarctions
- hemoglobin A1C,
- revascularization,
- etc, etc, etc
are literally all affected positively (to the benefit of the imaginary "mean" patient) in bulk.
Note though, that doesn't mean 100% of patients are have positive results, just that each of these are, in bulk, positive across the tested subjects when averaged together. There's little in the data to suggest that cases like your family member aren't happening or couldn't happen.
There's also evidence that GLP-1 agonists increase the rate of glucose use in the brain, accelerating learning rates. (The brain accounts for 2% of body weight but up to 25% of glucose consumption, it really is fueled by glucose)
Your relative’s sad story reminds me of a short story I read a few years ago about a miracle pill that leaves about 90% of its takers perfectly slim and able to stay that way eating anything, after a few truly disgusting initial days of elimination, but kills the other 10% gruesomely.
Because it’s so wonderfully effective for the majority, there ends up being a ton of social and economic pressure for anyone even slightly overweight to take it, despite said 10% risk of death.
I have to admit, I would probably have taken the pill depending on how gruesome (or mitigatible) the death is. I've been obese and I've been thin, and life is not worth living when obese.
10 years ago, I was reading about nootropics and ran across an interesting piece on the ethics of drugs (that has probably been lost to time). The question it was asking was "why can we take drugs to bring us to normal, but we can't take drugs that make us better than normal?"
The interesting consequence is that it de facto forces people who don't need drugs to take them or be at a disadvantage. (think adderall at a competitive college or testosterone for lifting).
> The question it was asking was "why can we take drugs to bring us to normal, but we can't take drugs that make us better than normal?"
Because ultimately drugs make you pay one way or another, eg dependency, liver toxicity, numbness of some other facet and so on. When none of those will be true it’s the day they become the new norm
True, but the price vs the amount of effect varies hugely.
Some drugs are a bargain. Caffeine. E-nicotine. Some are hellishly expensive. Solvents will destroy your health without even giving much in the way of a high.
Great story. There were parts that made me think the pill was a metaphor for the covid vaccine, but this story was written several months before the vaccine was released
About 6 months ago there was a posting about Ozempic and I had said something to the effect that it wasn't worth it watching some of the side effects my wife had from it. And then I went to the doctor for a check-up and lo and behold I had diabetes. Asymptomatic, but an A1C of 11. My doctor re-ran the test because he didn't believe it and it doesn't run in my family. My cholesterol had also jumped and he said he was going to put me on a statin after the initial 3 months of adjusting to the diabetes medication.
My Dr. puts me on Ozempic and I grumble about it but with that test results I had, I knew I had to do something. Fast forward 3 months, I dropped 20 pounds, and every other measurement is back in the green, including my A1C. Now, I made some serious lifestyle changes and ate a diabetic diet (limiting carbs, the types of carbs, etc), and have been keeping up with being more active but my entire relationship with food has changed because of Ozempic. Before I had a near compulsion to eat more than I should. Now, I don't because one, I feel fuller quicker and two, I know I'll feel horrible for hours if I over-eat. It only took one of those events to never want to do that again. I can't really explain why but I also don't have as strong of a desire to eat foods that are bad for me. I really thought I'd battle the cravings more after going cold turkey from "bad" foods. I can't say why it is but it's true. Side note, going to the grocery story was really difficult at first....there is so much sugar in the American food supply.
Energy wise I will say that I did struggle with low energy initially as my body adapted to lower calorie intake but I also learned that when I found the right balance of protein/complex carbs for me that my energy levels came back up and I now feel better than ever.
My doctor was shocked. I've never seen him that animated when I came back in for the 3 month follow-up. I didn't need to add any additional medications and they're slowly adjusting me back towards a single medication.
Out of curiosity, do you drink much water each day?
I'm kind of wondering if the people having a bad result don't drink enough water each day to clear out their systems? Yeah, that's a simplistic take... but still, curiosity. :)
Yeah, most of the time I think I do. I suspect it has to do more with diet and maybe water as well. Since Ozempic slows down your digestive process my current thought is that fiber / gut bacteria might have more affect on things but I haven't done a food diary to try and track what impacts me more.
Has nothing to do with it. A1c measures the percentage of hemoglobin A1 in red blood cells bound to sugars (glycated hemoglobin). Since red blood cells normally circulate for months this gives a surrogate marker for average blood glucose levels over 3-6 months.
Dehydration is not a confounder for an A1c test since the percentage is relative to the hemoglobin present. The primary confounder to A1c are blood disorders such as hemolytic anemias that lower the normal lifetime of RBCs or proportion of HbA. And this tends to falsely lower the A1c.
A person with an 11% A1c is also likely drinking quite a bit (whether they notice it or not) because at that point the chronically elevated glucose is elevating serum osmolality to increase urination.
Dehydration and kidney damage is a common side effect of Semaglutide, and they regularly test for that if you are on it. Drinking plenty of water is the way to prevent that from happening.
Perhaps I misunderstood what the GP was asking. Nevertheless GLP-1 medications appear to be kidney protective from a long term standpoint with an increased short term risk of AKI likely primarily related to GI losses with additional risk conveyed by concomitant use of “depleting” (diuretics) and nephrotoxic meds. Once on a stable dose there’s no current recommendation to monitor kidney function beyond what would normally be indicated for diabetes (usually yearly).
As a counterpoint, I've been using it for several months and have had no side effects to speak of other than occasionally some mild reflux.
If anything, my energy levels actually went up immediately after starting it. Normally I was pretty sluggish but it felt like some extra firepower was unlocked.
Everything has risks and benefits, and might harm some people. I hope your family member gets better soon.
I’ve been on it (at 1mg, then 2mg doses) for 3-4 years now. Worst side effect for me is the tendency to have sulfur smelling burps if I have any kind of stomach upset.
Second the question about tolerance! Wondering why this doesnt happen it is interesting. Most everything else causes some tolerance over time but no one mentions it for this
I take it, and when I started I got violently nauseous and had GI issues. I wasn't informed I needed to slowly ramp up.
I still have pretty big appetite suppression, and only minimal nausea sometimes if I eat too much, but what it's done to my blood glucose is AMAZING. And I lost some weight when I started which was a great bonus. It can be hard to start but it's truly worth it, just adjust the dose. I take 0.5mg as I can't handle the larger 1.0mg dose.
In a fair world that would be considered severe malpractice :-( It's nearly common knowledge. A huge number of people are suffering under these medications because of starting at a dose to high or raising doses too quickly / too much at a time.
LY3437943 looks even more promising, with fewer side effects. Semaglutide will probably have the most side effects because it only has one action (GLP-1 agonist). Tirzepatide has slightly lower side effects because it adds a dual action (GLP-1 agonist + GIP analogue) so it can act at a lower magnitude on the GLP-1 receptors to avoid strong side effects, while still having higher efficacy due to its additional, separate, GIP action.
LY3437943 retains both the actions of Tirzepatide but adds a third action, glucagon receptor agonist. So it should be able to have higher efficacy at a lower equivalent dose than the other two (less action on GLP-1 and GIP mechanisms, fewer side effects).
The risk of pancreatitis is also increased substantially [0]. And for people who may already be predisposed to pancreatitis but haven’t had an attack, severe pancreatitis has a 10-30% mortality rate [1]. But even mild acute pancreatitis will make you want to crawl out of your own skin in pain.
out of an n of >3000 patients getting medication, 34 ended up having some form of pancreatitis. At least 12 people on placebo got pancreatitis. That's a much higher rate, but the odds are still pretty low.
I'm somewhat dubious of the severe pancreatitis mortality rates-- the issue is that most cases of severe pancreatitis are caused by very severe alcoholism, and by the time the pancreatitis shows up everything else is already failing.
That’s not entirely true. Pancreatitis, especially necrotizing pancreatitis, actually causes the broad systemic organ dysfunction. So even alcoholics with fine organs can end up with liver, lung, heart, kidney, etc complications from a severe bout of pancreatitis. Even basic things like fluid balance and endocrine function can be thrown way off by both the disease and treatment (large amounts of fluid resuscitation). I recently had severe bouts of non-alcoholic pancreatitis, the worst of which ended in a 3 month hospital stay with various periods on ventilators and various organ dysfunction. My imaging and bloodwork from 3 weeks prior were clean (I do them routinely since the pancreatitis is recurring).
Reminds me of the first FDA approved weight loss drug, Alli, that basically just gastrointestinally punishes you if you eat more than a few grams of fat.
My favorite fat loss drug along these lines is dinitrophenol. It is the true miracle fat burning drug. It interferes with cellular metabolism in such a way that the body just nonstop oxidizes fat. Fat mass loss in the order of a pound a day or more is entirely possible and some bodybuilders use it to get to a ludicrously low bodyfat percentage. Unfortunately oxidizing that much fat generates a lot of heat, so much that an overdose can be lethal because your body literally roasts itself to death and titration is extremely difficult. Oh and blindness is a common side effect. And for added fun it’s an high explosive. Needless to say it’s not FDA approved.
Honestly GLP-1 agonists will save lives just by being the go-to replacement for people who previously would have used DNP. GLP-1 agonists are effective enough that everyone in those circles basically stopped using DNP suddenly a couple years ago.
Never trust a fart on orlistat. The horror stories I’ve read of people soiling themselves after eating seemingly normal meals is nuts. On par with Olestra/Haribo sugar-free stories. Also it makes absorbing fat soluble vitamins a huge issue.
> The manual for Alli makes it clear that orlistat treatment involves aversion therapy, encouraging the user to associate eating fat with unpleasant treatment effects.
Christ. This is like Crohn's disease in pill form. One too many teaspoons of olive oil and you're in for an unpleasant evening...
I don't have a colon (but I do still have a functioning anus). The effects from orlistat are very similar to what I experience 24/7. If you're under 30 or so, eventually your sphincter gets much, much stronger and the excess oil stops affecting you nearly as much. You can hold it in indefinitely until your normal "need to go" timing. This takes about a year or so to train, and you'll have quite a few accidents in the meantime.
I still can't eat too much salmon in one sitting though :-( I don't get diarrhea but I do get stuck on the toilet for ages after.
There’s huge tradeoffs people rarely talk about in Medicine. Significant risk of soiling yourself vs a statistically significant reduction in risk of early death isn’t a big deal for the FDA.
In many cases the hell that is chemo is considered acceptable for even moderate increases in expected lifespan. That’s why people started talking healthy life expectancy vs just life expectancy.
You want to know what's even crazier, you can literally but it over the counter. I was at kroger the other day and I saw it next to the vitamins and I did a double take.
Yeah, that's definitely always been my challenge with weight loss. I have zero problem with self control -- I can easily cut calories in half or less (e.g. 1000-1200 cal/day), but it's simply that my body suffers immensely. I lose all energy, can't concentrate on anything, and my immune system weakens so I start getting colds constantly.
I'm sure I'd easily lose weight with Ozempic but I'd still be suffering health issues. Not because of Ozempic itself but just because I wouldn't be getting enough calories, despite still being above a healthy weight.
You may have better success in a smaller caloric deficit. 1000-1200 calories a day is very few and that’s a very fast pace of weight loss. Try removing 500 calories or 10% of your calories. Progress will be slower, but you may feel much better.
Also, as a sibling comment alluded to, when you have fewer calories to eat, the micronutrients in the few foods you do eat matter that much more. The nutritional quality of food you need to stay healthy increases greatly when in a caloric deficit. Fruits and veggies are great for helping that, and multivitamins are cheap insurance policies to make sure you aren’t deficient in anything important, IMO. YMMV. Best of luck with your goals!
Does the same thing happen if you slowly wean yourself down? Are you cutting out essential nutrients that your body needs to function properly rather than the unnecessary carbs/junk? The reason I'm asking these things is that people I know who have reduced their caloric intake usually report feeling better, not worse.
Calories are not created equal. They are equal in physics sense, but your body is not a "bomb calorimeter" (device to measure caloric content of whatever). So maybe instead of cutting your calories in half, you cut less and replace carb calories with fat calories or protein calories.
Or maybe you can even cut to 1000-1200 by replacing your calorie source with something else. For some weird reason carrots with butter work very well for me and I love the taste :-)
That reaction may have to do with too much cutting, as another commenter alluded to, but it may also have to do with the types of nutrients you are missing when cutting.
I started Wegovy about 5 months ago. The first couple months you feel sick but after it passes your appetite is extremely curbed (in a good way). Would highly recommend people to try it as it's made me healthier in pretty much every way.
I know this isn't your family member, but if they were a 500-pound alcoholic smoking two packs of cigarettes a day, I suspect they probably felt like crap before the ozempic.
Not helpful. Drugs are drugs. Side effect happens. Sometimes not even related to the drug.
I don't know how you folks do it in the US, but I imagine there is a leaflet attached to the medication, and somewhere in it should be a phone number, physical address and/or an e-mail address of an institution that tracks drug side effects. If you're unlucky enough to have some weird reaction to a drug, it's good to let them know.
It’s interesting to me how much of the hostility to this drug has a moral dimension. I am quite fit for my middle age. It’s a relative superpower which confers a degree of status in this world. It’s not why I originally became fit 5 or so years ago but it’s something I increasingly notice or to be clear others notice and comment on.
I think the “fit” of the world get inherently uncomfortable that our relative social currency is being “devalued” if everyone can be like us with an “unearned” pill. And it comes out as hostility and skepticism.
I admit haven’t done much research on this particular topic. History should caution us that serious medication like this often has serious side effects which are not apparent early on. I get that. But unlike many others I don’t “hope” that happens like some kind of moral balancing. I get that reaction. In my gut I have that “I did it with willpower and lifestyle and sweat and these people shouldn’t just get it at CVS.” But that’s just the primate status brain talking.
Not that it impacts the outcome but I sincerely hope these drugs can improve people’s lives without significant negative problems. I can find my relative status elsewhere or better yet try to grow up past such impulses.
Well said. I believe you are right. That and ignorance of how Leptin works, setpoint or lipostat theory of bodyweight regulation...once you've gotten fat, your setpoint goes up and the hunger signals are far greater than folks who have never gotten fat. You can have 2 athletes with identical weight height and BF%, but if one had been fat once, their hunger signals from the brain will be far greater than the athlete who was always slim.
Those of us that work out, however, have been dealing with 'cheating with drugs' for a while: steroids. When you get close with enough gym rats, it's utterly shocking how many people with a muscular build use steroids. It's to the point where I essentially don't believe anyone claiming 'natty' (natural) status if they have more than a 1 sigma increase in musculature.
It's also downright laughable how the media/Youtube influencers/etc. treat everyone like idiots. Men's Health will run an article on Mr. Moviestar who was 5'11' and 150 pounds before his role as Superhero Character got to 200 pounds and veiny biceps in 6 months by eating eggs, oatmeal, and chicken breast and doing some situps.
Not literally, but it's really, really awful for society to have no idea what physiques/transformations required AAS and which didn't. That type of misinformation should not be allowed, and it would be amazing if there were a reasonable way to ban mass media lying / misrepresentation. Unfortunately, any law like that would instantly get weaponized to obliterate any remaining first amendment protections.
It's crazy how many athletes I tried to keep up with at D2/D3 schools which I now realize were on heavy steroid cycles but at the time I just thought I wasn't eating enough / had bad genetics / whatever.
It's also interesting how the negative effects of light/moderate steroid use are really blown out of proportion, and how many men on "TRT" are getting their testosterone to twice the highest "normal" levels (e.g. reaching testosterone levels of 1500-2000) under a doctor's recommendation.
And men just blame themselves their whole life for simply not trying hard enough.
When I finally started TRT at the relatively very low dose of 120mg/week I laughed/cried for months at how insanely easy it was to build real muscle for the first time in my life. Training at 15-25% of the intensity that I used to over the past 20 years yielded 400% better results.
Yes. On a compounded semaglutide. I can finally control my hunger and a nice unexpected effect has been losing a desire to drink large quantities of alcohol. I don’t drink during the week anyway, but it seems to be the volume that turns me off to drinking. Thus a few cocktails are all I can tolerate. For context, Im 30, male, would be defined as a binge drinker on weekends. Oh, and I’ve given up nicotine entirely. I can’t tell if the drug is helping or it was just a point in my life that I finally decided I accept it makes me feel ill most of the time.
I'd hazard a guess that nicotine is one of the two or three most addictive substances known to humanity. Opiates/heroin is probably worse, world of warcraft is probably third :-)
Society makes it hard as well. It’s unacceptable to be falling asleep high on opiates. Hitting a vape on a video call with coworkers is considerably more acceptable.
As a fully remote employee for years who now lives in zoom I have never seen a coworker hit a vape on a call and it would be very off putting if they did, in the same way smoking a cig while on a call would be.
I've seen coworkers do it accidentally, forgetting their cameras are on. It's a super hard habit to quit, too, since it's innocuous (except you can't leave home without your vape!).
Nicotine was the hardest thing I have ever given up - three years later and I still get the occasional craving or dream where I have an excuse to smoke. This tracks with the experience of other smokes I have known. All else being equal and given you have reason to believe the drug reduces cravings, I'd guess that it is a strong factor
A drug that promotes weight loss, lessens the desire to smoke, drink, etc...sounds too good to be true?
From what I have heard, all of these issues come back as soon as someone comes off the drug. So either a person is committing to a lifetime of being dependent on this drug, or a person is committing to some period of time of ideal living, followed by a possible time of depression after reverting to the status quo.
I'm not sure why "it stops working when you stop taking it" is used as an argument against these new peptides. This is the way almost every medication we encounter works.
Tylenol might get rid of your headache, but that headache can come back tomorrow. Stop taking birth control and you might get pregnant. Stop taking Claritin and your allergies return. Stop taking insulin, and, as with these new peptides, you lose control over your blood sugar. Stop taking Adderall, and not only will your ADHD symptoms come back, you'll also experience withdrawal.
Almost no medications are "one and done", and I'm not sure why Ozempic or Mounjaro are being held to needing to be a cure when it's clear that they're effective, repeatable treatments for blood sugar control and (likely related) weight gain.
I am not holding Ozempic to needing to be the cure for anything. My point is that people without diabetes are looking to this drug for weight loss, at which point they create a dangerous dependency, with no hard evidence that their actual health improves. This is opposed to coming up with long term solutions that involve re-evaluating daily decisions that lead to some of these diseases in the first place. If Ozempic is a good treatment for blood sugar control, which could be a good factor to consider in weight fluctuation, maybe reduce the amount of sugar one eats?
Is it really a dangerous dependency? There's been no evidence of anything happening once individuals go off of semaglutide or tirzepatide other than the tendency of gaining weight to the original levels and/or blood sugar readings returning to the pre-medication levels. This is the most common outcome anyone has trying literally any calorie-reducing diet, medication or not. There's no evidence that people are ending up worse for having been on the medication, except for some who experience gastro effects early on and can simply quit.
Also, yes, you can absolutely advocate for a low-carb/low-sugar diet for those with poor blood sugar control. The issue there is that virtually every medical professional has advocated for similar diets for diabetics or those with blood sugar control issues for centuries, or even millennia - there is evidence of recommended diets for those with diabetes since BCE. This does not mean that those diets are easy or pleasant to follow, whereas all evidence indicates that common issues with appetite and energy on a limited calorie or low-carb diet are less prevalent with these new peptides than those trying to go it alone.
I don’t necessarily mean dangerous in the health aspect, although long term affects of these drugs are not know yet…I mean the dependency on needed the drug to keep a certain lifestyle, and then having an “oh shit” moment when you’re in a place that you can’t access it, whether that be traveling or the supply of it becomes scarce, or it gets banned, etc
That sounds like the lesser of two evils to me. Get healthier now and maybe sometime later lose access to the thing that helps you be healthier...or don't get healthier now? Yeah, there are other, orthogonal, choices but I don't think they're part of this particular decision matrix.
I lost about 15-20 kg on Ozempic over about six months to a year, and held that weight for another year – continuing on 1 mg Ozempic / wk – until last autumn (2022). Then Ozempic was more widely approved than it had been before somewhere (for over-the-counter sales in the USA? Something like that.), and became unavailable in pharmacies where I live, in Finland. (AIUI, because it's more lucrative to sell it in the USA where prices aren't regulated like here, so all the limited supply is redirected there.) No problem, I was prescribed a substitute, a daily pill (brandname Rybelsus, forgot the active substance) in stead of the weekly injection pen. Worked the same, held my weight. (More of a hassle to take though, and tastes horribly, so on the whole I vastly prefer the Ozempic.)
Then, earlier this spring, that prescription ran out. Being in the middle of changing my primary healthcare provider I couldn't immediately get it renewed. And to be honest I wasn't at first all that bothered; I thought now that I've lost so much weight, and kept it off for so long with the help of these drugs, maybe I've got into the habit of eating less, so I can stay constant without them? Nope – in just a few weeks, ballooned back up some 8-10 kg. Had to scramble a bit to get the pill prescription renewed, been on it again for a couple weeks, but still some 6-7 kg above where I was before they ran out. Sure hope I'll get back down the rest of the way.
TLDR: Anecdata (n=1) says yes, going off the drugs even for a rather short while puts the weight back on quite quickly.
An average person would have to eat 5500 kcal per day to gain this much weight in a month. It's probably not impossible, but I would say it is very unlikely.
But given that the actual health benefits of ozempic(for me weight loss is not indicative of better health) have not actually been seen yet, you are quite possibly just taking on both evils at the same time.
On the contrary: GLP1 agonists show broad health benefits across the board.
Check this 24-month clinical trial with >3000 participants[0]. It showed improvements in rates of:
- Cardiovascular death
- Non-fatal Myocardial Infarction
- Non-fatal Stroke
- Revascularisation
- HbA1c
- Fasting Plasma Glucose
- Body Weight
- Lipid Profile ( total cholesterol, LDL cholesterol and triglycerides)
- Urinary Albumin to Creatinine Ratio
- Systolic blood pressure (mmHg)
- "overall health related quality of life namely bodily pain, general health, mental component summary, mental health, physical component summary, physical functioning, role-emotional, role-physical, social functioning and vitality." (each of these categories were "quantitatively" measured using a calibrated questionnaire - - and they all showed a dose-response relationship -- 1.0mg semaglutide made a bigger improvement than 0.5 mg, vs. two different placebos)
>the dependency on needed the drug to keep a certain lifestyle, and then having an “oh shit” moment when you’re in a place that you can’t access it, whether that be traveling or the supply of it becomes scarce, or it gets banned, etc
It sounds like you're realizing what it's like to really depend on a medication.
The anxieties and risks you're describing are what people with diabetes, cancer, HIV, bipolar disorder, schizophrenia, depression, ADHD, etc. deal with on a daily basis for their entire life.
Yeah, it is frightening! Sometimes a guy like this[0] comes along and makes your life even worse!
How dangerous is it to have a new $1k/month bill you need to pay forever?
So far there is no indication insurance companies are going to pay for 100 million Americans going on Ozempic who aren't diabetic...
Anecdotally, another danger is people confusing less eating with a healthy diet. I know someone on Ozempic...eats less but what is eaten is the same old junk...
Given a significant percent of voters are overweight and obese, it would be very politically popular to legislate that health insurance must pay for GLP-1 antagonists.
No. The additional costs to the healthcare system due to people being overweight probably exceed 12000/person/year, but if not exceed it, they certainly come close. Moreover, it's not unheard of to mandate cheaper drug prices, and now that we understand how these drugs work, there will be more of them in the pipeline.
> The additional costs to the healthcare system due to people being overweight probably exceed 12000/person/year
This is a big claim to assert without evidence. If it was the case then insurers would already be adding the drugs to their formularies.
There is undoubtedly a cost associated with obesity but you are suggesting that simply being overweight doubles the average cost of care[1], a figure that already includes overweight and obese people (which are of course a huge population in the US).
A quick Google search turned up a report[2] that suggests that
> This estimated public cost equates to an average marginal cost of $175 per year per adult for a one unit change in BMI for each adult in the U.S. population.
So, even for the extreme case of a very obese person that has a very successful treatment and goes from 40 BMI to 25 BMI, you are only saving a hypothetical $2,625 per year (perhaps an underestimate due to inflation and the age of the paper).
Therefore it would appear that unless insurers strike a deal with the drug companies (lower the price, make it up in volume), such a law would dramatically increase insurance premiums. A better compromise would be a law which requires insurance companies to offer co-insurance on these drugs up to the expected savings.
> If it was the case then insurers would already be adding the drugs to their formularies.
American healthcare system has perverse incentivizes. Most unhealthy groups are generally least likely to be privately insured, so insurers are incentivized to prioritize health issues affecting working-age adults, while neglecting those which will be someone's else concern in future.
Why would a $1k/month drug increase costs more compared to the status quo of expensive bariatric surgeries and complicated heart failure/joint issues/osteoarthritis/sleep apnea etc. cases that arise from obesity? Massively reducing obesity rates seems like a good thing from the POV of an insurer.
> So far there is no indication insurance companies are going to pay for 100 million Americans going on Ozempic who aren't diabetic...
What’s the cost/benefit of weight loss and diabetes control vs $12k/year? I would expect people with high obesity are very expensive to insure and insurance can’t drop people any more. It may be cheaper to pay for ozempic (especially at whatever negotiated rate insurance pays) than to pay for the alternative negative health outcomes.
That and ozempic goes generic in 2031 and mounjaro in 2027 so soon this won’t be a question of $1000/month but maybe $1000/year at which point insurers will probably force customers to take it or pay higher rates.
> Anecdotally, another danger is people confusing less eating with a healthy diet. I know someone on Ozempic...eats less but what is eaten is the same old junk...
There is anecdotal evidence that eating less is, in itself, so much more healthy that it doesn't really matter what you eat. Nutrition professor Mark Haub ate nothing but "convenience store food" for 10 weeks at a caloric deficit and all of his health metrics improved while he lost 27lbs.
> My point is that people without diabetes are looking to this drug for weight loss, at which point they create a dangerous dependency, with no hard evidence that their actual health improves.
These drugs would have to be pretty bad to counteract the massive health benefits from losing weight (even if they don't have diabetes). I've heard a few eye-openers in the comments, but unless they're more prevalent than I've read, or there's some ticking time bomb, the drugs are probably still a net health benefit.
> This is opposed to coming up with long term solutions that involve re-evaluating daily decisions that lead to some of these diseases in the first place.
Medicine tried this. It's extremely hard to actually to do it in practice. Obviously, it's better solution, but we are living in real world, where we have to choose "good enough" solutions over those deemed "better, but infeasible for 90% of patients".
"re-evaluating daily decisions" is exactly what suppressing these hormones allow people to do; so that they can make rational instead of hormone driven decisions.
(If the answer is "because you'll learn to eat less or eat in a more healthy fashion", it may well be that the metabolic issues that are creating heightened blood sugar or appetite issues may not be able to be resolved by diet alone in those who respond well to these peptides.)
>From what I have heard, all of these issues come back as soon as someone comes off the drug. So either a person is committing to a lifetime of being dependent on this drug, or a person is committing to some period of time of ideal living, followed by a possible time of depression after reverting to the status quo.
This is true of every weight loss intervention: Weight Watchers, low-carb, keto, Whole 30, etc. Once people stop complying with them, they gain the weight back.
Most people don't realize how dismal the stats on long-term weight loss are. Almost no one maintains a substantial amount of weight loss for many years by following "just eat healthy and exercise" advice. The only intervention that does reliably work is bariatric surgery. The jury is still out on the new GLP drugs.
> The only intervention that does reliably work is bariatric surgery.
My understanding is surgery only works reliably because failure to comply with life style changes post-op is easily fatal and ethical doctors only perform the operation after patients have demonstrated that ability. In all but the most extreme patients, about a fifth to a third of the target weight loss has to happen pre-op for doctors to even consider the procedure. The surgery is essentially a sword of Damocles hanging over patients, reminding them that they'll die much faster than normal if they over eat.
Failure to comply with the post op diet might be fatal within the first few months of recovery (although I haven't heard of that happening, I'm sure someone has died from eating too much), but after that, you are going to be mostly healed up. And its the long term that will determine if the weight loss sticks. It certainly isn't just because the surgery selects for people with willpower. Because almost everyone who has it has gone through years of losing and gaining back their weight over and over.
Bariatric surgery usually works for 3 reasons. First and most obvious is that it reduces your stomach size so you simply can't eat as much. Second, in most cases, reducing the surface area of the stomach reduces the amount of hunger hormones that get released thus making you less hungry all the time. And the third is malabsorption. Meaning that of the food you do eat, you absorb less of the calories than you did before. So if it were possible, you could potentially eat the same amount as before but still lose weight.
In the addiction literature, the development of gambling dependence after bariatric surgery is limited. Mitchel et al. reported that 2 cases presented with post-operative gambling addiction in their 3-year screening study in 201 post-op case (5). In our case, the presence of genetic background may be a risk factor for the develop-ment of gambling
2 out of 200 cases is not that common and close to baseline level
Clinically, what causes the urge to have an addiction? Like in your statement, replacing food with gambling. I would assume that these are fundamentally two different reward systems for the brain, or maybe not?
The first days, weeks and months are often the hardest time when quitting a substance. If this drug helps a smoker not smoke for 3 months, by that time the nicotine addiction has weakened considerably. They've gotten past the hardest part. I see no downside to that.
Similarly, if a person loses 30 pounds on this drug, then stops using the drug and reverts to normal habits, it will take a while to regain those 30 pounds. And the long term shift of maintaining the new body weight doesn't require any radical changes (unlike losing 30 pounds, which does require sustained radical changes).
That is not what happened to me. I took it for 2 months and then I wanted to get off. I did not go back to normal. Mentally I felt like I needed more food and more junk food than I ever did before using the drug.
My hypothesis is that it supressed my body's natural production of whatever chemical in my brain helps me not go overboard with food. With that supressed by the drug I had an uncontrollable desire for food and currently I am fatter than I was before taking the drug in the first place.
Did you quit cold turkey? Or did you slowly taper it off?
I'm taking Rybelsus (pill form of semaglutide) and there are 3, 7 and 14 mg versions. My plan is to take 14 mg for a couple more months, then switch to 7 mg for 1-2 months and then 3 mg for a month before stopping taking it completely.
> Mentally I felt like I needed more food and more junk food than I ever did before using the drug
This is consistent with hungry brain hypothesis. Your hypothalamus detects that you have less body fat than amount set on "lipostat" and it tries to get fat content back to this set amount.
An interaction with leptin? Or are you just feeling hungry after the side effects wore off?
You also said it stopped working while you were taking it in another post; are you just talking about satiety or one of the other effects like insulin production or glucagon release? Are you diabetic or just overweight?
This is what I thought as well, that the habits that drive some of these activities would be dramatically weakened, but it looks like the body is not actually re-aligning to a new homeostatis level, so when a person gets off the drug, the body is trying to get back to the old level. I don't think it all comes back to habits, often your body is working really hard against you to get back a level it feels is right(whether that level is 'healthy' or not).
> The first days, weeks and months are often the hardest time when quitting a substance. If this drug helps a smoker not smoke for 3 months, by that time the nicotine addiction has weakened considerably.
I love(d) nicotine and it was the only substance that I ever was addicted to.
I tried dozens of times to quit and the only thing that helped was getting treatment for my ADHD.
Quitting nicotine was easy for me on methylphenidate.
I only tried combining them and nearly went to the ER, so I quickly learnt that I can't take them both.
But when I'm on methylphenidate I just don't crave nicotine that much.
It took 2-3 years to completely not get any nicotine cravings at all.
I describe my adhd as being addicted to nicotine and stopping cold turkey. Except you're not addicted to nicotine, what you're addicted to is a stimulus that is inconsistent and changes constantly. Your cigarette is a constantly changing thing.
Methylphenidate really messed me up, I found Lisdexamfetamine much much more effective.
I still use nicotine, though in vape form these days.
Not the person you're replying to, but what helped me quit was the book "How to stop smoking" by Alan Carr. Highly recommend working through it and taking his point about cold turkey in good faith. Good luck!
I have a fun experience with the Alan Carr book. The first time I read it, I was laughing the whole way through thinking about how much it was written like straight-up brainwashing propaganda, but I had committed to a friend to reading it all the way through. I got to the end where the final bit is something like "now just say out loud 'I am a non-smoker and when I wake up tomorrow I will never have a cigarette again'". I chuckled, thought it was ridiculous, and the next morning I woke up and didn't have a smoke. That lasted about 2 years until I got extremely drunk one night after a rough breakup, had smoked the whole night, and was pretty much instantly hooked again.
Ten years later I went through the exercise again, but sadly it didn't work nearly as well as it had the first time around.
One thing that kind of opened my eyes is his asking the reader "what do you prefer about your cigarette brand?" It made me realize that they all taste like sh*t.
In my experience, different drugs have different effects on different people, sometimes radically so, and overly-generalizing is less than useless when trying to learn and understand how drugs work, both on an individual level and a societal level.
Imagine being 250 lbs and feeling like you are starving constantly, despite eating a lot every day. You decide to lose weight. You do something you hate, like calorie restriction and working out like a dog. You lose 80 lbs in 1 year. Bravo. Everyone tells you how great you look. You feel great. All that hard work was worth it. The fatness and a million other things really motivated you to do the hard work. I've done this a couple of times.
Next day after hitting your goal, the starvation is still there. The desire to eat is still there. Hating working out is still there. But now you have to do this herculean effort every day not to get better. Not to lose weight. Just to maintain. Your brain wants you to gain 80 lbs and will never stop nagging you. Not on a good day. Not on a bad day.
Then something really shitty happens in your life. Like it does for everyone. You slip. Eventually you start to gain back the weight. You just want to die. You feel like a failure. You hate yourself.
That's the trick. Hitting goal weight the first time or two is relatively "easy". But you've achieved nothing if you aren't able to maintain weight loss. That's the failure of all approaches prior to these GLP1 and similar drugs.
Having set the scene, now compare it to semaglutide. You have a drug that regulates your brain. Gets rid of the constant nagging to eat. You get normal brain. You lose weight.
Now you have to pick, take a once a week drug for life to maintain, or do a herculean effort to fight the brain urges and work out to maintain.
This perfectly encapsulates my experience. I'm hesitant to ask for this medication because of side effects and because it's got a 2 year limit in my country, so I don't want to go through it all then have to stop and ultimately put it all back on. Shit sucks, bro.
Do some research into compound pharmacies as a worst picture backup. I know several people on them successfully. Peptides can't be patented. Semaglutide is a peptide. They are patenting the delivery mechanism AFAICT. As to sides, ramp up slowly. Maybe you won't have any. Also, there are new drugs coming that are even better. I'm sure the shortages and whatnot will be sorted out. The solution is out there. They can't stop this train.
This is...mostly wrong. Like both normal wrong, and "x-y problem" wrong. There is definitely some truth in there, but the full explanation would require an actual lawyer, because there's a LOT of layers of complication.
Just so people don't have to simply take my word against yours, here's Jacob Sherkow, JD, a professor of law and medicine at the Illinois College of Medicine on the topic:
> semaglutide that's "made, used, sold, offered to be sold, or imported into the United States is possibly an act of infringement, if Novo were to sue them"
But this isn't just about patents -- that's the "x-y problem" that I was talking about. It may not be legal to import active ingredients of FDA-approved drugs. Most peptides (AOC-9604, BPC-157, Ibutamoren, Ipamorelin, etc) are "legal" because they're not considered drugs. Once they're FDA approved, they become not legal to import/re-sell unless you're a compounding pharmacy. It wouldn't generally be legal to import fexofenadine (OTC allergy medication), for example, even though it's not a controlled substance. Because importing non-FDA drugs is generally not legal unless you're a licensed part of the medical supply chain.
So yes, compounding pharmacies can provide it to you and you offload the legal gray areas onto them. But just saying "they can't be patented" kind of hides most of the legal quandaries. From a practical perspective, many organizations and individuals do import these things without worrying about legal consequences, because enforcement is very low. But I wouldn't formally pretend the legal issues don't exist at all levels.
Look, I read a bunch of contradictory stuff on the internet about this and am close to a good number of people in healthcare who told me compound pharmacies are legit and that there's a lot of FUD on the internet.
But I'm not pretending to be an expert in law or medicine.
People need to research this and do what they feel comfortable with.
That said, I'd personally prefer if the prices came down, the supply remained highly available and it was covered by insurance and the companies like Novo who spent money to create these solutions got paid for it. It's a miracle and they deserve what money they make off it.
To your point, there is a ton of gray area. One site I can responsibly link here is https://www.peptidesciences.com/ -- they're very careful about working to stay on the right side of the law, and they sell semaglutide and tirzepatide for ostensibly "not-for-human-consumption" (and at very, very high prices). So the raw ingredient, in non-medical settings, is not inherently impossible to import and sell legally. But I'm not fully convinced they're immune to lawsuits or legal action.
I'm gonna end the conversation here and let you have the last word, because I don't even feel comfortable talking about compounding pharmas.
From what I've read, sites like the above are really dangerous, because people are ordering from them and like you said, are NOT for human consumption.
Compound pharmacies, from what I understand, are meant for human consumption. From the healthcare people I know personally, including my own doctor, they have been used for ages and are totally legit. But folks should just talk to their doctor before taking anything.
This is exactly what happened to me. The clinic I went to recommended starting out with 1/10 the normal dose for the first month to make sure I would tolerate it. Then we would move up each month.
It worked so well I didn't want to move up so for month 2 I stuck with 1/10th the amount. During that month the effects wore off so I had to take more to get the same impact. I chose to just quit.
2 months after quiting I am 7 pounds fatter than I was when I started with the drug. I suspect that most people will need to keep taking more and more of it to get the same benefits they got from the recommended dose. I am really concerned this is going to lead to a bigger health crises than the one it purported to solve.
> I am really concerned this is going to lead to a bigger health crises than the one it purported to solve.
A lot of diabetics taking it to regulate blood sugar (particular the feedback loop with insulin and hunger) have said it's changed their life... but for people who are merely overweight I think the benefits may not always be worth the side effects. IMO the correlation between weight and health is not as strong as people often assume.
Anecdotal, but if you looked at me and my partner, you'd probably assume I was the "healthier" one based on our respective body types. But they're strong, fit, and rarely get sick (knock on wood); meanwhile I'm a lifelong wimp with a host of autoimmune issues. I outsource all of the heavy lifting to them, literally—if the trash is too heavy for me to take to the dumpster, they get to do it instead :P
So to your point about health crises, yeah. It seems foolish to put my partner on a weight loss drug just so they could "look" healthier while nursing a bunch of unpleasant side effects that would make them far sicker than they were before.
Sure, but that doesn't mean everyone who's overweight has high blood pressure and therefore should go on "shit your brains out" medication.
EDIT: Also, to my previous anecdote, despite being the skinny one compared to my partner, I actually do have several heart problems! (Thank you inflammatory diseases.) But you wouldn't guess that by looking at me, because weight is not a 1:1 indicator of health.
I think weight is the wrong thing to target for gauging health, but it is the thing that is in everyone's face and easy to see. Undernourishment is just a big of a problem as over-nourishment. Targeting the four horsemen(t2 diabetes, Alzheimer's, heart disease, cancer) is a better use of time and money, but they are relatively much harder to identify early.
> Undernourishment is just a big of a problem as over-nourishment.
Having been recently diagnosed with Crohn's I 100% agree. Getting skinnier during a bad flare makes people think I'm in better health, because I look a certain way that aligns with their expectations, but it really just means my gut isn't absorbing any nutrients. Turns out being at my lowest weight in years was a Very Bad Thing and not a sign I was doing anything right.
Which, again, is an interesting juxtaposition with my partner who weighs more than me but whose body functions correctly and whose biomarkers come back normal, unlike mine.
> Targeting the four horsemen(t2 diabetes, Alzheimer's, heart disease, cancer) is a better use of time and money, but they are relatively much harder to identify early.
All of these diseases have significant input from bad diet and metabolic disorder. Alzheimer's is considered a variation of t2d in some circles.
> A drug that promotes weight loss, lessens the desire to smoke, drink, etc...sounds too good to be true?
It does sound too good to be true. However, it's possible that the drug is working on all of these through the same mechanism: by altering the brain's reward system.
If that's true, the drug doesn't make you not want to eat, it makes you not want stuff, in general. That could potentially suppress a wide array of addictive behaviors. I also wonder if that suppression might look a lot like clinical depression, though.
Reports from people using this don't indicate that they feel depressed at all. They either get a ton of nausea if their dose is too high, or they just don't get cravings to eat tons of "bad" food. Most people I've talked with on low doses report they can still eat large meals, but it has to be a pretty conscious, determined decision.
No one's been reporting depression that I've seen. And these groups ('fitness enthusiasts') experiment with enough other things that do cause depression that they're quite sensitive to changes in "well-being", "outlook on life", "mood", and "energy levels". It would be more widely reported in these circles if it did resemble depression.
For a lot of people, it's kind of a choice of which substance you are going to be dependent on. It's all expensive and sad, but between Ozempic and cigarettes, alcohol, or overeating, Ozempic has got to be healthier, and quite possibly cheaper in the long run.
I took it and started out with a small dose. The impact of that dose wore off eventually and the plan at my clinic was to raise it over time.
I am concerned that maybe there isn't a dose where you can stop taking more and keep the results. I am worried that everybody will need to keep taking more as they build up more tolerance to it. The study that showed how effective the drug is was 60 weeks long.
That is a long time, but it doesn't show what happens if somebody plans on staying on the drug for years.
Most research indicates "yes", conditioned on the consensus of what comprises the modern lifestyle.
I've been trying to understand what changed to create the obesity epidemic. Many things contribute, but it's hard to identify the smoking gun. My understanding is that one major lever seems to be the advent of snacks, refrigeration, and microwaves. Drastically reduced food prep overhead has radically alerted eating patterns.
It seems pretty obvious that the massive injection of sugar in the 60s and 70s into diets paved the way for pretty much everything else that followed(snacks, fast food, convenient food, etc). I guess we can all ignore that diabetes is driven by insulin resistance and the body's inability to process glucose, which is conveniently also the predominant thing in our food today, because we would rather look the other way and continue living in a fairy tale...that is until we are disease ridden in our 40s, at which point we can live out the rest of our lives on meds and in the hospital.
To pile on other popular theories on smoking guns, there is a widespread decrease in physical activity levels. Physical activity can delay or prevent type 2 diabetes, as well as having widespread benefits on almost every system of the body. Physical activity also improves mental health, which impacts some behaviors around emotional/addiction driven over eating.
I doubt we do more physical activity now than people did in the 70s and 80s.
Sure, people may go to the gym more... But they also take the lift or the escalator in stead of the stairs much more, and the car in stead of a bicycle or walking. Any source for your claim?
Versus, like, "just suck it up"? No, but empirically that strategy has had poor results across the wider population. It seems like it would work, but usually doesn't. At some point people look for more effective strategies.
Healthier in what sense? There is little knowledge of long term side effects and it isn't even approved for weight loss, it is specifically for people with diabetes.
Semaglutide, the active ingredient in Ozempic, is absolutely approved in the US for weight loss. Ozempic is the trade name for the diabetes medication, Wegovy is the trade name for the weight loss medication. They are the exact same medication, in the same formulation.
What if the greatest harm is that the easy path of modifying our biology prevents us ever needing to gain the self-knowledge and build the fulfilling lives that lets us thrive in a world surrounded by potential addictions?
I consider myself a much wiser and stronger person in recovery than I was before addiction. Who would I be if I took a magic pill and was still the person that sought oblivion? What will humanity be if it doesn't need such self-knowledge and resilience? What impact will that make in say, our future politics?
This feels like the same logic as "I had to pay off my student loans, so other people should have to suffer like that too." Suffering does not make you better later despite what millennia of Christian theology has told people about its supposed purgative effects. It seems pretty rad to me to be able to just not suffer through the bad part of getting over a major life problem, and I for one am happy that people will be able to skip that part and get on to the part where they live well.
This is not an argument that suffering is valuable, it's that drug-seeking behaviours are a symptom of poor psychology / life-fulfilment.
The fear is that by removing symptoms, we no longer find it important to address the root cause. The symptoms should be treated as a warning signal. It sounds dystopian to make poor psychology and poor life-fulfilment a consequence free norm.
> A drug that promotes weight loss, lessens the desire to smoke, drink, etc...sounds too good to be true?
What other desires does it lessen? Does it suppress every hedonistic impulse? What does it do to creativity? Impulsivity? Does it make you more susceptible to or resistant to persuasion? Feels like reporting ‘oh it has these other unintended psychological/behavioral responses. Neat!’ is ignoring a whole can of worms that that opens.
I think the body of work around what this drug does outside of its impact on patients with diabetes is pretty limited, which is what is scary about everyone jumping on this one.
A lot of addiction is caused by social issues or mental health issues, but it's really hard to deal with those issues when someone is also dealing with the effects of addiction. A drug like this could provide an opportunity to fix the underlying issues causing addiction in the first place.
And for some people they will have to take this for life, which isn't so different from many other medications.
Yeah, I honestly don’t see a problem with taking a drug for life, as long as the side effects are minimal and the logistics are simple. I’m in my early 30’s and have a family history of bad cholesterol. So once a day I will take a statin for the rest of my life. Not a problem, little to no side effects and pretty easy to manage, and not the end of the world if I miss one day every so often. Twice a day is not so easy to manage and plan but once a day is definitely manageable for a lot of people
Could be worse. Omeprazole not only stops working after you get off it, your issues actually become much more severe. Once you're on it, you are unlikely to ever be able to get off of it.
do you have stats to confirm your assertion about this drug because it seems as speculation as saying "well maybe if I was 100lbs less I would have more energy, be happier with myself and therefore have more willpower to have a more healthy relationship with food".
The same could be said even for interventions like "don't eat surplus calories" and "life weights". Once you stop, you don't get the benefits and you'll regress.
"But you have to do it forever" shouldn't be a convincing dismissal after 10 seconds of thought.
What happens when you reach your target weight with drugs like this?
After having learned potentionally nothing about nutrition, exercise, and self-control, are you stuck on these meds for life out of fear of binge-eating back to your original weight?
FWIW I'm on a hundred-pound roller coaster ride from 300lbs to 200lbs; currently ~215. I've learned a lot about discipline and sustainable habits along the way.
I’ve never been obese but after losing 30+ lbs of weight I found it a lot easier to live an active lifestyle and keep the weight off. Partly it was just that moving around was physically easier and less strenuous, but also that I was less self conscious and had higher self esteem.
I imagine Ozempic will help with this even if people don’t learn about nutrition per se. Though I think basically everybody knows nutrition, it’s more about self control IME.
What happens when someone who was previously deeply depressed but feels better goes off an antidepressant? They learn to handle life, or they return to the drug if further treatment is needed. It’s not a moral failing.
As an anecdote: at my worst (when I was clearly suicidal, insomniac and emotionally unstable) I was on antidepressants (Prozac) and it helped me a lot. It made me very emotionally stable. I got off Prozac after a couple years to try it out and I felt much better. Over that year, I started feeling similarly terrible due to COVID world. Went back to Prozac. Once again made me very stable. Stopped using Prozac in mid 2022, again to see if I feel good without it. Since then have been feeling much, much better. Of course, mental health is a constant battle, you fight one day at a time, but I consider my depression as close to "cured" as possible because over the last year I felt pretty normal without any drugs.
Things to note are, along the way I stopped drinking alcohol which helped me tons. Before 2020 I was a huge drinker (not alcoholic, but every day heavy drinker). Initially, I started smoking weed. This helped a ton because I stopped drinking completely, but I wasn't getting very high every day and I thought THC helped quite a bit too. Eventually, in late 2022 I stopped using THC too. I'm completely drug free now. I believe that both Prozac and THC helped me significantly to get out of depression. In addition to drugs, CBT (cognitive behavioral therapy), therapy in general and getting a cat has been extremely helpful as well.
This is just an anecdote, every brain is different. Never self medicate, see a doctor and a therapist!
I don't think you need to bring morality into it. OP is just asking, do you develop your own tools to address the problem, or rely on another's forever? There are lots of practical non-moral answers to that question.
Presumably the dose can be altered such that for a given individual their appetite creates a caloric equilibrium at close to the target weight. I don't think this is something that is done currently.
The side effects of chronic use don't appear to be that significant and would need to be weighed against the side effects of chronic obesity.
Semaglutide gets all the press because it's a lot cheaper and actually available (barely available, but available). Tirzepatide is much more difficult to get access to, though IMO it should be the one that people default to if they're going to take this class of drug.
Semaglutide will probably have the most side effects because it only has one action (GLP-1 agonist). Tirzepatide has slightly lower side effects because it adds a dual action (GLP-1 agonist + GIP analogue) so it can act at a lower magnitude on the GLP-1 receptors to avoid strong side effects, while still having higher efficacy due to its additional, separate, GIP action.
LY3437943 looks even more promising, with fewer side effects. LY3437943 retains both the actions of Tirzepatide but adds a third action, glucagon receptor agonist. So it should be able to have higher efficacy at a lower equivalent dose than the other two (less action on GLP-1 and GIP mechanisms, fewer side effects).
Ozempic has been around longer and there were a bunch of celebrities taking it and talking about it on twitter so I think it has more cultural cachet. Most people probably don't know about mounjaro, I don't even think it's approved for weight loss yet.
Mounjaro is not yet approved for weight loss in the US even though there is strong evidence that it will be, and there's little question that there has generally been weight loss in those taking it for diabetes.
Recent studies have very clearly shown it's effective for weight loss even in those without diabetes, but there's a lag as the FDA reviews those studies. Until then, Lilly simply can't advertise it as a treatment for obesity.
It’s not weird at all if you’re aware of the regulations.
Drug companies can’t promote a drug for something it’s not FDA approved for (off-label promotion). Companies face multi-billion dollar penalties for doing so.
Mounjaro is approved for type 2 diabetes. And weight loss is a great way to help get your type 2 diabetes under control.
So highlighting that it helps type 2 patients lose weight, while having an FDA mandated disclosure that it’s not approved for weight loss alone, makes perfect sense.
How long is the research info ozempic and other hormonal weight loss drugs? Remember the last miracle drug that went to the market for weight loss had to be retracted for killing people or damaging their hearts to the tune of over 10 billion dollars in damages paid out.
Drugs acting on GLP-1 (ozempic), GIP, and glucagon receptors are largely shown to help hearts and cardiovascular health specifically (and independently of weight loss). They also improve lipid profiles (HDL/LDL), and have a multitude of other benefits.
Whether they, for example, increase the rate of glial brain cancer ... they really haven't been out long enough to know.
While I am not saying that this drug is definitely safe, I think the fact that Fen-phen turned out to be more dangerous doesn't really implicate these new drugs because while the desired outcome is the same, the class and type of drugs seem to be entirely different. My understanding is that fen-phen is a stimulant and increased blood pressure and heart rate. It also includes some other drugs that affect serotonin levels.
These new drugs are peptide analogs that affect your body's digestion and how it deals with sugar and fat production and insulin.
I tried Ozempic for two months but wasn't able to continue - the gastrointestinal side effects are unbearable. I can confirm lack of desire to eat and drink alcohol. The hunger didn't go away but after a few bites of anything it quickly evaporated. After dropping the drug the hunger steeply increased, even higher than before, that was hard to contain.
the genetics of obesity are amazing.
we all have a unique combination of genes, and epigenic features that influece the endocrine and neuronal pathways that drive the desire to eat, these different genotypes affect our behaviour. Ozempic is putting a thumb on the scales of this pathway, but this pathway is balanced differently in all of us.
Think of the most hungry you have ever been, in some people this never stops, in others it's dialed up or down.
there are some great papers on fat labradors that hint at how these different genotypes are linked to our desire to eat and how that shifts our behaiour.
Guide dogs are highly selected for trainability, and positive reinforcement with food reward plays an important role in their training.
I think it was Yeo, found 22% of pet Labradors and 80% of Labrador guide dogs sampled carried a 14 BP deletion in the POMC gene, which forms part of this pathway.
Moralizing about weight loss is upsetting, as someone whose thankfully considers themselves "naturally thin".
It's 100% true the vast majority (including me) needs to put some discipline into eating and exercise: normal people can't just eat whatever they want whenever they feel hungry. But normal people don't get fat eating whole foods, working out, eating below their demographic's daily intake; and normal people don't suffer immense fatigue on tiny calorie deficits or even maintenance. People with thyroid and other metabolic issues do. Which IMO completely destroys the "moral" argument for weight.
(And it's also probably true that most overweight people don't eat whole foods and work out daily. That doesn't mean its right to call out some random fat person eating a mildly-unhealthy meal. You have no idea what else they've eaten that day, what else is going on around them, and you wouldn't call out a skinny person who eats the same.)
I'm a person who has vacillated between being close to normal weight and obese. I think people who don't have problems controlling their diet tend to underestimate just how hard it can be to eat at a calorie deficit or even just maintenance when you've lost a large amount of weight. When I'm at my lowest weight I literally am thinking about food constantly and my maintenance calorie intake drops to about 1500-1800 calories.
"processed" food is fine - all food is processed. The issue is with huge amounts of fast carbs coupled with high fat. It can occur even with "unprocessed" foods such ice cream.
It's also interesting to note that while thyroid and other similar issues are not usually the cause of a person's initial weight gain, those types of issues are much more common in obese people. So it makes it much more likely that an obese person has some underlying medical issues making their battle to lose weight even more difficult.
I was always of the opinion that being fat was a moral failing. Trying the drug really changed that.
Normies have it so easy. They take one bite and feel full. My brain would scream at me continuously to try and make me eat and would never be satisfied.
"they take one bite and feel full"- I strongly disagree with this as the reason some people are just lean.
As someone who's bounced around weight a lot and also had long periods where I had to basically control it (wrestling in college), the main difference I've seen with people who are in shape and people are overeat is that the former group understands that it's 'ok' to not feel full all the time. As in like learning the TRUE difference between appetite and hunger.
I've had periods where I gained 50lb in like 4 months (start of pandemic) and all I had to do to basically get back to baseline is remind myself that I'm not going to die just bc I'm not constantly full.
But i definitely don't get 'full' after a few bites. I can keep eating and eating for sure. It's more that being what we call traditionally "full" is actually just wayyyyy overeating.
When I'm on vacation my stress is reduced to the point where my 'appetite' drops, and this is despite the fact that I'm increasing my exercise load enormously (surfing, hiking, etc...)
I've noticed that stress causes me mild stomach pain, which can register as hunger. It also causes dry mouth which registers as thirst. If you're satisfying that thirst with sugary drinks long term, then you're going to be in trouble.
There is also so much novelty and more interesting stuff going on while on vacation that I don't find myself poking through the fridge out of boredom.
I also lose so much weight on vacation it's weird. I once lost weight when visiting Japan for two weeks but I swore I was going crazy with the food, so I was confused. But I still managed to eat less than at home (I must have). Definitely a busyness thing.
Im the opposite when it comes to stress. I lose my appetite when I'm stressed but get super super hungry when bored. The lockdowns really messed up my eating habits but thankfully I've shed all the weight now that I can actually do stuff again.
Oh buddy... you're not normal. If you're yoyoing 50 pounds then you also have the eating disorder.
Trust me on this. I also thought it was a self-control thing. It's not at all. When you're normal you actually get full. I don't mean telling yourself you are full, actually full. You do not want to eat anymore. You don't want chocolate straight after eating dinner. You don't go to the fridge randomly to get snacks. You actually have no desire for food. You voluntarily stop eating during meals because you don't want to eat anymore.
It's something you can't really comprehend without experiencing it because you've experienced a lifetime of the hunger constantly telling you to eat. The idea that you could just... not want to eat is just absurd. But that's how it feels. When a normal person eats a small meal and says they are full, they are actually full. There's no self-control for them, no screaming voice or impulses.
Miswrote: I don't yo-yo 50lb normally. Only once during the pandemic gained that much and I was purposely eating like shit bc I was angry with the lockdown situation and had nothing else to do. Just used that as an example that if I actually just eat as much as I want (like eat till I'm full-full 3x a day) with no control, I'd be 50lb heavier. But 95% of my adult life post college (9+ years), I hover around the same weight.
I guess I understand what you mean that you'd think that every skinny person must actually be full after eating and that's why they're like that, but everyone I know who is in shape (like really in shape, either ex college athlete or lives the gym life now and would be considered top 5% of the population), they absolutely do not feel full every meal/day. I mean talking about planning cheat meals and fantasizing about certain foods is super common in the fitness lifestyle.
I've met maybe 3 people in my entire life who have what you're describing: they truly don't care about food and can forget to eat meals if distracted. All the others have some form of habit/routine and wish they could eat more and stay lean.
I'm not discounting that some people really struggle with eating habits and literally cannot stop thinking to eat more (I have family members like that) but I do heavily disagree that 'normal' people are always full quickly and that's why they are 'normal' weight.
If it was a simple normal/not normal appetite wiring then why do most major cities contain way more skinny people and places like Mississippi are almost 50% obese? Or the fact that obesity was pretty rare 100 years ago. I think there's a lot more going on than just 'normal people get full quicker'.
I was about to get on semaglutide and after extensive research I thought "wait, the results won't be much better than the periods of IF I've had in the past, and the reported benefits are similar", and without side effects. Dropping 30 pounds in 3 months? easy to achieve with the Warrior Diet or OMAD versions of IF.
The results are exactly the same... you fill full eating less quantity, cravings disappear after 1-2 weeks, increased focus and enhanced mental state. But yeah, you need some self-discipline, tons of coffee/matcha and water.
I've concluded that semaglutide is not for me. Just like self-discipline in pills, with potential side effects. So better to give IF another go... I'm in the 4th week and dropped 10lbs already.
I am taking Contrave to lose weight. Lost 30 lbs in 4 months. It is a drug that's composed of an anti-depressant and an opioid antagonist. Together they have a synergistic effect that represses binging envy and cuts appetite.
It also has a repressive effect on drinking and smoke, to my great surprise. And it also has had an effect on my addiction to video games.
Drugs companies get a lot of slack (most of the time deserving) but sometimes they create miracles pills.
You can get these wholesale from China from "reputable" gray-market wholesalers who get the chemicals made at contract manufacturing facilities. BYO QA/QC though, as with all non-FDA drugs. That's the huge catch, and it sucks for consumers. Testing just for active ingredient is >$100 and takes about a month. Testing for proper buffering agents, harmful contaminants, microbial contamination, etc is essentially unavailable at all.
Semaglutide is very, very cheap in the gray market. It's somewhat less effective than Tirzepatide and has slightly more side effects if you ramp up the dosage too quickly.
If an annual amount is purchased on the gray market, this brings the monthly cost down to:
- Semaglutide: $10/month
- Tirzepatide: $60/month
- Liraglutide: $87/month
- LY3437943: I have not yet seen this available, but it looks like distributors are notifying manufacturers of latent demand and are working to build up a supply chain.
Note that in the USA, it is legal to import certain amounts of FDA-approved drugs if you have a prescription for them. However, just because something is the exact same chemical as an FDA-approved drug does not make it an FDA-approved drug. It must be manufactured in an FDA certified facility and be the same brand/manufacturer/packaging/labeling/etc as the approved drug.
e.g. importing generic Sildenafil/Viagra is legal if you can find the Teva(tm) brand generic sildenafil in, say, Mexico or Canada for a better price. But it must be the pills manufactured by Teva in the appropriate facility with NDC #0093-5342-56[0].
If you import generic sildenafil "Cenforce" from the (very legitimate but not FDA-approved) Indian pharmaceutical manufacturer "Centurion Laboratories"...
...that would still be potentially criminal smuggling. Even if the pills you import show via laboratory test that they precisely match your medical prescription, they are not "FDA approved" and therefore not legal to import.
Going to be huge when it goes off patent off exclusivity. I'd also expect you'll be able to get it when it's made in jurisdictions that will ignore the patent. Up to you to get it from those places, either via mail or travel runs.
not entirely true. semaglutide is a great example. the FDA allows compounding pharmacies to make semaglutide because wegovy/ozempic are sold out and therefore have limited availability. compounding pharmacies are allowed to sell their own royalty-free in this situation! wellsrx does just this (probably with chinese sourced semaglutide)
Also, I expect CRISPR or gene therapy to be the long game wrt this and updating the body's GLP-1 regulation, versus maintenance doses of a pharma product. This is a shim.
It is not possible to stop people from getting mail order pills from China. Especially with the abortion restrictions the market already is pretty large and it will be easy for them to throw these drugs in too.
The solution to that was a $10 per month subscription via Netflix and clips for free on YouTube. Meanwhile Ozempic is around $1,000 for a month's supply. That is a margin on par with illegal hard drugs, which already have a smuggling supply chain from China to North America (eg. Fentanyl and variants).
GLP-1 agonists are a bit more tricky since they are temperature sensitive and need to be injected. You'll really need to be careful to keep it sterile and handle it properly. Whether the "research chemical" will receive the proper care until it gets into your hands is something that you're literally gambling your health on.
You ship it as a dry/lypohilized powder, both semaglutide and tirzepatide survives long China->Europe shipping in the summer just fine, with customs delays. The testing I've seen showed 99.965% purity of semaglutide after 22 days in shipping from China to Poland during April. Tirzepatide shows 99.064% purity after 58 days of shipping in October-November. These didn't start out at 100.00% purity either, so they likely experienced absolutely minimal degradation in shipment.
You reconstitute it with Bacteriostatic Water which is available without a prescription in the USA and contains 0.9% benzyl alcohol to inhibit bacterial growth.
If you're particularly concerned you buy a 0.22 micrometer PVDF "syringe filter" and pump it through that to another, fresh/sealed sterile vial which you can get for like $2.00 from a medical supply company (the syringe, filter, and vials are gamma-irradiated to destroy any remnants of RNA/DNA). That size filtration will filter out any lifeforms (fungal, bacterial, viral) while allowing the peptide/drug itself to pass through. So you get a guaranteed sterile solution out of the filter.
> That size filtration will filter out any lifeforms (fungal, bacterial, viral) while allowing the peptide/drug itself to pass through
0.22 won't filter out viruses, but time will inactivate enveloped viruses (which are usually the ones you want to avoid injecting), and source control/proper handling should take care of the rest.
Anything specific would be inappropriate for this forum. But the broad answer is a chemicals distributor in China. I actually only utilize them for legal "nutritional" compounds, but others use them for pharmaceutical options, and those are independently tested frequently by a variety of stakeholders. Personally I really wish US citizens didn't feel forced to go outside of the quality protections of the FDA for their medical care.
Nutritional compounds? My understanding is that without a lot of special processing, GLP-1 agonists (semiglutide, liraglutide, tirzepatide, etc) will be degraded by stomach acids into useless fragments. There's an oral semiglutide formulation but it looks like it's quite inefficient and has some pretty strigent requirements in order to be effective.
What? No one is taking these orally. Hence the bacteriostatic water for injection.
The same distributor sells legal things to import like L-Carnitine, Epitalon, Berberine, NAD+, NACET, and vitamins at great prices so I was saying I use them for things like that.
But others use them for GLP-1 agonists and many do their own independent testing.
FWIW, SubQ injections are pretty much completely unnoticeable in terms of pain / feeling at all. It’s more the mental barrier of doing it to yourself but once you’ve done it for the first time you soon realise it’s fine.
The actual doing it seems wild/absurd, but I don't think that would hold me back.
This is ignorant/uniformed, but, taking research chemical by ingestion feels like I have some natural barriers still. Where-as I feel like there's a much more raw exposure to risk with injection. Also there's dumb risks like infection, if I don't attend well enough to injections.
In spite of these protests, I think you are probably much closer to the truth here. Thanks for writing. These reactions I have are, I suspect, not really significant.
It's not the only GLP-1 agonist out there. Victoza is another GLP-1 agonist and should be going generic in the US in a little over a year. It might already be available as a generic outside the US. There might be other GLP-1 agonists that are going generic soon as well.
it's funny in that a few years ago we were (and still are) excited by the potential cellular protective properties of GLP1 agonists, not just in the pancreas but in brain glial cells or whatnot. So much so that it seems to be the most neuroprotective of recent candidates for Parkinson's disease disease-modifying-therapies (DMTs).
to whit, (like botox), all the initial promises of the stuff have been waaaay overshadowed by...cosmetic value.
(I'm oversimplifying a bit...for those who are morbidly obese, yes, the weight loss really helps, but then they also have diabetes most likely which is the primary indication of the drug)
edit: many point out calorie intake is the real problem, it's true: buy a kitchen scale, weigh your food, count your calories, and you will lose weight. Exercise is optional compared to that. Still, both are free and have more benefits.
Exercise does nothing for weight loss if you're eating too much. Exercise has health benefits, but weight loss is not one of them for the vast majority of people. People wildly overestimate how many calories they're burning.
> People wildly overestimate how many calories they're burning.
And people wildly underestimate how many calories they need. Just by limiting the one portion to 50g of pasta, instead of my preferred 150+g, I can go under 100kg in less than a week. My 'how much should I cook' habits formed when I was young and spent at least a couple of hours commuting, but nowadays I'm quite literally just sit on my ass all day. It's bothersome and isn't fulfilling to use scales cut down on the food (especially if it's tasty) but...
Exercise can help control hunger and insulin levels so it's a good idea to pair moderate exercise with diet. I find it harder to resist snacking when I'm not regularly exercising.
Calories can still be a useful metric as a proxy but low calorie (“diet”) foods tend to compensate with more carbs. At least the ones I see regularly at my grocery store.
As a side note: It’s actually difficult to find pre-packaged low carb food at regular grocery stores sadly. It requires effort to make yourself, just like going to the gym. Like most good things in life.
They're not mutually exclusive. You can exercise regularly and still have a substance abuse problem. In fact, substance abuse is a major problem amongst high-performing athletes [1]
Exercise is not an effective weight loss intervention. It's something you should do for your cardiovascular health, strength, and cardiovascular health.
> And that works for what, 3% of the people that try it?
Exercise is medicine!
Far too few people understand that unfortunately. Something is wrong with our culture when the majority have the attitude that exercise isn't worth doing.
Exercise has many side effects too, including a risk of injury.
Meanwhile GLP-1 protects and even improves the function of brain, lungs, heart, muscles, bones, and kidneys, it improves sleep quality and reduces sleep duration, it definitely decreases addictive behavior, and even seems to help with some immune issues (anecdotally, but the effect is so strong it’s remarkable).
> Exercise has many side effects too, including a risk of injury.
This feels like saying chocking is a side effect of eating vegetables.
Most negative side effects from exercise come in a few camps.
* The exercise of choice comes with a risk of accidents. Accidents happen everywhere, but they happen to skiers more frequently than mall power walkers.
* The exercise of choice is well known to put strain on certain body parts. Usually this is a joint or tendon. Pitchers and arms. Power lifting and knees.
* The exerciser did not prepare well for exercise. Do they have proper equipment? Did they stretch? Did they warm up? Did they drink enough fluid? Are they attempting a goal they aren't ready for? Are they over training? Did they get training to establish proper technique? Are they distracted when they should have been focused?
> This feels like saying chocking is a side effect of eating vegetables.
That’s actually my point. HN not getting anything that isn’t straightforward though is expected.
The side effect profile of these modern drugs is actually shockingly minimal so I felt the GP post was doing much the same as people who would claim exercise has side effects - missing the forest for the trees. Everything has side effects but if something has an overwhelmingly positive effect profile with seemingly minor side effects the discussion shouldn’t be misdirected like they were trying to do.
From my experience of addiction, suppressing the sensation of pleasure derived, is only the start.
People who are addicted will repeat the behaviour even without the neurochemical response. Consider the ritual of the addiction as a form of self-soothing.
You have to treat the patterns we've trod in our own minds, as well as removing that biological reinforcement.
So, instead is suppressing the desire to eat, how about inventing a drug that blocks the absorption or breakdown of carbohydrates in the gut? Or maybe control the gut biome so that growth of bacteria that breaks down high calorie food is minimized.
Is this faster-than-light-like impossible daydream or is there any plausible path to it?
Your first proposal is what acarbose does. It is widely used in Asia, but is much less popular in Western countries. It inhibits alpha glucosidase and alpha amylase, which has the effect of decreasing the rate that complex carbohydates are broken down and absorbed.
Consider Alli, the drug that blocks fat absorption in the body. It already exists and works reasonably well for weight loss. The side effects can be gross and unpleasant though.
Imagine the side effects of food passing through the gut without being broken down.
Reminds me of Olestra, the zero calorie oil substitute that failed because of similar sounding side effects. Olestra wasn't consumed/absorbed in the gut so you'd just shit out oil and your half digested food would glide out with it since it didn't block stomach emptying like real food.
Some people will tell you though that they can eat anything and not put on weight - this is simply allowing others to do the same, right.
A vomitorium is simply the large exit pathway in stadia for rapid egress of many people. The idea that ancient Romans had facilities dedicated to vomiting has been debunked.
That's why I said (real), I know they didn't exist - though I'm guessing somewhere, sometime in history it has.
Those people that tell you they can eat anything and not put on weight have a very different idea of what "anything" is than fat people, with probably an actual exception here and there (along with teenagers).
I mean the opposite where we're fattening up ourselves like lambs for the slaughter isn't working out great either. We've had recent downward trend in longevity.
Is this mostly a US drug? I never heard about it in France.
I can't believe people love it so much without thinking about the actual source of their problem.
The source of the problem is that animals are wired to eat as much food as possible as quickly as possible.
You can't blame half of the population for something that is deeply wired into our brain and bodies.
I think you can ultimately blame them, but you can also accept that for many it's a very difficult problem to overcome and that finding other ways to tackle it has value to the individual and community.
Just a heads up “weight loss” is a poor metric if it comes at the cost of lean muscle mass. It seems that 39% of weight loss associated with Ozempic comes from lean muscle mass which isn’t great.
When you diet to lose weight you lose lean muscle too unless you exercise to minimize it. What's the lean muscle mass loss from just dieting? I would guess that it's a relatively large number too.
I’m generally skeptical of pharmaceutical weight loss solutions as a bandaid over the underlying problem, but for this statement to mean anything you’d have to compare it to traditional methods of weight loss.
If you simply eat at a calorie deficit and aren’t taking specific steps to preserve muscle (resistance training and high protein), a lot of the weight you lose will be muscle mass.
Though a certain amount of lean loss is inevitable with significant weight reduction (usually about 25% of total weight loss), the goal is to increase the body’s overall proportion of lean mass – in other words, to improve body composition.
In 2020, Diabetologia published a body composition analysis of 88 volunteers with type 2 diabetes who used semaglutide for one year. These participants lost an average of 12.5 pounds. Of that weight loss, there was a 7.5-pound reduction in fat mass and a 5-pound reduction in lean mass.
In 2021, a major trial of semaglutide’s weight loss potency examined the body composition of a minority of participants. These patients did not have diabetes, and they took a much larger dose of the drug. The 95 participants to undergo a body scan lost an average of 18 pounds of fat — and 12 pounds of lean mass.
Wegovy- semaglutide- is approved for weight loss "in adults with obesity or overweight with at least one weight-related condition (such as high blood pressure, type 2 diabetes, or high cholesterol)":
Ivermectin did feasibly improve covid outcomes, but only in places where worms were common, which is not the US.
So it's true that people like the one you are responding to are ignorant and can't really understand nuance and that they are also wrong for their lack of trust in institutions, but institutions also failed to communicate to those ignorant people and that is a problem all of it's own.
Very fun science read that I hope humbles you a little:
Unfortunately, suggesting that people eat less and exercise more doesn’t seem to actually work that well. We’ve been trying that for decades and the obesity epidemic just keeps getting worse.
Have we though? I seriously doubt doctors are aggressively pushing eating well and exercising. Has anyone ever received a workout plan from their doctor besides some generic PT exercises? Do they develop nutrition plans tailored to you? Do they track your progress? Do they have any incentive for you to actually get better? Do they require regular blood tests and include all the tests that might actually tell them something?
The answer is a resounding no. None of that. Even if you request a blood test, they will include the absolute bare minimum and fight you when you request something like vitamin D or testosterone. General healthcare in the US is farce. You must be your own doctor, do your own research and fight for the care you need and also tolerate doctors telling you that you don't know what you're talking about. Besides being prescribed antibiotics, no doctor has ever fixed any problem I've ever had. I had to do it myself.
I seriously doubt doctors are aggressively pushing eating well and exercising.
Have you ever... been to a doctor when you've been obese? I assure you that they will indeed push eating well and exercising to obese people. Even when you've already been eating well and exercising. This will not be an intervention by the PCP themselves - your primary can really just refer people to substantial interventions - but they will try to refer you to one of three things.
First, they will recommend a book on healthy eating and exercising.
Second, there is behavioral weight loss, which generally is a combination of an appetite-suppression medication like phentermine and a Very Low Calorie Diet through a pre-made controlled calorie diet (such as Medifast or Optifast). A program like this will absolutely require weigh-ins and blood tests.
Third, they will recommend surgical weight loss, most likely gastric bypass, such as Roux-en-Y. There are guaranteed to be medical follow-ups after the surgery.
If you are not clinically obese, and that's great, no, your PCP will not provide that type of advice. They're not there to help you with subclinical concerns with weight. There are plenty of dietitians out there who can.
Anyway, that's not a resounding no - it is extremely common to be referred to these programs if you have any substantial level of obesity. If you're obese, and you haven't been referred to these programs by your PCP, that might be an issue with your primary.
What's exciting about these new peptides is that a simple once-a-week injection might be able to be prescribed by a primary with limited intervention or without outside specialists or surgery and still have good results in terms of weight-loss, as opposed to the truly exhausting requirements of a medically-assisted VLCD or weight loss surgery.
Finally, I have no idea what you're talking about Vitamin D. I've both been diagnosed with a Vitamin D deficiency by my primary (through blood tests!), and Vitamin D supplements are easily available over the counter without a prescription.
If you are not clinically obese, and that's great, no, your PCP will not provide that type of advice. They're not there to help you with subclinical concerns with weight. There are plenty of dietitians out there who can.
yeah. If you are losing weight unintentionally, docs will care a lot and will run tests. Otherwise, being overweight, not so much. Weight loss is a bigger concern than weight gain from the perspective of doctors.
Legally in some states some doctors are mandated to bring up weight loss to sufficiently fat patients. But also, fat loss isn’t covered by insurance generally unless it’s paired with an existing health condition. So fat people who don’t have health problems don’t get help to lose weight but get all the shame. :)
Vacuously false. Do you think "eat well and exercise regularly" is some kind of magic switch? One day you are 120lbs overweight but then you eat well and exercise for a week and star in a film?
Probably because people aren't acting on it, or sticking with it long enough to actually see results.
Especially in today's world when they can just take a pill and loose 10-15 pounds, nobody wants to do something they probably don't like doing (consistent exercise or healthy eating) as part of a short-term or long-term process.
A lot of people, especially those in food deserts or without access to adequate nutrition on a consistent basis (or those who cannot afford quality food, or those unable to prepare it properly) are not going to undergo something where change is gradual versus taking a magic pill, side effects be damned. Sad, but that's the world we live in.
Weight has been increasing for nearly 40 years now in the US among all groups. Trying to point this out as any kind of individual failure just has not, and is not going to work. It's tantamount to telling someone to stop smoking in 1950. Yes, some people did manage to, but the vast majority stopped smoking when their lungs no longer supported them living.
When pretty much everywhere you go is plastered in signs saying "EAT THIS YUMMY UNHEALTHY BULLSHIT" and said bullshit is cheap and highly available don't be surprised when we have society wide problems. Add to that our work practices commonly have us hold down a computer for 8 hours a day, it should be no surprise we are where we are.
A small group that's used a different selection mechanism than the primary population is really a poor metric to judge the majority. It seems likely that we'd find that migrant populations that have to a lot of work to get where they are have a higher motivation level than the general population.
One should look at Asian obesity level growth, then compare the populations you're talking about in particular
Probably because people aren't acting on it, or sticking with it long enough to actually see results.
Like telling penguins they need to flap harder to fly. The literature on diets on abysmal. People lose some weight and regain it, probably as willpower runs out. Look at all these celebrity weight loss shows over the past 2 decades--almost every contestant regains the weight, and these are people who have a lot of money and access to top chefs, trainers, etc.
> Sad that the obvious route (diet and exercise) is skipped by so many people
Many people also try it repeatedly for several years or even decades, failing all the while. There's also psychological issues that make this hard (possibly among other issues), and no pithy remedy like "try diet and exercise" for that (well, ok, sometimes people say "try therapy" this way, but we can include people who've included that for several years too.)
I also think the problem is that if you’re losing weight, you’re by definition not eating healthy. If you could skip to the fat gone step, and work on a diet that maintains a healthy weight, it seems like you would have a easier time adjusting.
>Sad that the obvious route (diet and exercise) is skipped by so many people, who just want to continue their unhealthy lifestyles but not suffer the physical consequences of it.
Food has a different effects on different bodies with different mental state and neurochemistry. Pleasurable foods can be as addictive as recreational drugs. Is it really fair to blame it on people? When somebody can't stop using cocaine, we don't call them undisciplined, we call them addicts.
It is far better for somebody to use a crutch to lose weight than remain fat and significantly damage their health in turn reducing their lifespan. Increasing tax on unhealthy foods and reducing sugar is still a work in progress. The long term goal is to nudge people into healthier foods such that the cycle of addiction is harder to start.
With the collapse of traditional gender roles, both the man and a woman in a typical family are now working full time. It's harder particularly for the lower class to eat healthily when there's nobody to prepare meals. If that problem were solved, we'd be a big step closer to solving obesity.
> Sad that the obvious route (diet and exercise) is skipped by so many people
It is definitely true that many people find it difficult to be abjectly miserable all the time. The difference with Ozempic/Wegovy is (and I know this is hard to believe!) you can eat a small portion of something and actually feel satisfied and literally just not want more. This is mind-blowing when you've never experienced it before. I've only been on the lowest dose for a few weeks, and I'm still in shock about how effortless it is to just... stop. I actually can get satisfied with food, rather than feeling too full to eat more! I have been wondering if this is just what naturally thin people feel like all the time?
Yeah, it's weird, right? But people keep putting use-after-free bugs everywhere. Like, do the OpenBSD guys not know that this is a bug (and worse, a security bug)? They keep putting them everywhere. A few years ago they stuck one in OpenSMTPD.
Theo de Raadt would benefit from reading some Hacker News.
I'm a former alcoholic. I quit cold turkey years ago.
Had a drug problem before that. Cold turkey as well.
While I agree with you somewhat, I too don't like the narrative, I also realize that some people actually can't do that. Some people are faster, some smarter, some stronger, and some of us are better at sticking to a resolution. Everyone has things they're good at and things they struggle at despite the effort. Gotta find what works for you personally.
I'm happy you've quit your former habits and I celebrate you.
Just so you know, the point of my post isn't to rip on people with low willpower or to brag about mine (which would be false valor anyway--there are reasons I had issues with alcohol and drugs to begin with). The thesis of my post is that the narrative is that you need a drug to get better.
Ozempic is supposed to be a treatment applied to people who are not yet overweight enough for bariatric surgery, yet it is being used ubiquitously. What does that tell you about the mind share differences between "you need a drug to get better" versus "you can just stop"?
The idea that another drug is your only way out is but a shadow on the wall of a cave, puppeteered by Big Pharma, people need to free themselves, escape outside and see the sun.
Additionally, my post was "flagged" which is a bit hilarious. I wonder what part of my post was hateful or otherwise below the standards of this forum. Unless you define hate as being critical of big pharma.
> Just so you know, the point of my post isn't to rip on people with low willpower or to brag about mine
Sure came off that way though.
> Ozempic is supposed to be a treatment applied to people who are not yet overweight enough for bariatric surgery, yet it is being used ubiquitously.
Because being overweight, albeit not quite enough for bariatric surgery, is quite ubiquitous? Dunno for sure, but certainly feels rather plausible. Wouldn't you say?
> I wonder what part of my post was hateful or otherwise below the standards of this forum.
Probably the bit where you came off as an insufferably smug prick, saying “Why don't they just eat cak—” Oops, I mean “Why don't they just stop eating?”. Comes to about the same thing, votre Majesté.
I'm very happy for you that you beat alcoholism. it's a nasty beast. The rest of us are facing the ladder on the right for certain issues. It's time we take a deeper look at problems people face, and actually help them fix it rather than sit back and judge them for moral failings when in reality it turns out to be a brain chemistry thing that can't be helped.
I think a healthy dose of compassion is in order here.
It is well known that compulsive tendencies are, in some people, literal demons that want nothing more than to destroy your life, and do. There are degrees to things and 'willpower' is not so simple.
Congratulations. You were blessed with some very convenient brain chemistry. Many others are not so lucky, and literally cannot even begin to commit to decisions you find trivial.
It's probably impossible for you understand what it's like (which is good!) but for many people it's completely ineffective to use their free will to try and overcome the pull of their brain's reward system. That's when exogenous chemical assistance is needed.
Addicts know what needs to be done, can see the harmful effects of not doing it, but no amount of internal force can make it happen. Addiction is horrible.
Pharma is big money. This drug can cost 800-1400/month. Average American can't even run a mile. Patients dont want to hear how they need to eat less or exercise. Doctors have long queues of people to get through. Easier to prescribe the pill and move on vs address lifestyle choice.
Couldn’t agree more. Although I never suffered from obesity, I’ve lived a generally unhealthy lifestyle for most of my life. Slowly I’ve gotten my diet in order - not perfect, but a lot better.
I haven’t had a smoke for three days, and frankly, it was easier to quit than I thought. I still get the impulse to go buy a pack, but I hold out and 20 minutes later that intrusive thought is gone.
I don’t believe a pill would do much, in the end I needed to change
Even if a pill were the right solution, it wouldn't give you the personal growth that you are experiencing. Exercising your willpower in this way may allow you to increase your ability to make changes. These things can become easier with practice.
"Semaglutide does not dull all pleasure, people taking the drug for weight loss told me. They could still enjoy a few bites of food or revel in finding the perfect dress; they just no longer went overboard. Anhedonia, or a general diminished ability to experience pleasure, also hasn’t shown up in cohorts of people who take the drug for diabetes, says Elisabet Jerlhag Holm, an addiction researcher at the University of Gothenburg."
So it doesn't dull all pleasure just almost all so it's not technically anhedonia...
Our experience exists on a series of spectrums, some people experience pleasure way too intensely and it actually causes problems which is why this might be a good thing
Obviously there are people who like the pleasure given to them by food a bit too much and they consistently overindulge, it can be that way for many things as well. I'm not saying that the cause is always related but for many it may be
I'm not sure it is pleasure driving people to go overboard. I'm pretty sure it is dissatisfaction that is driving excess. In which case a drug that means you're more easily satisfied is far from bleak.
If anything the opposite is far more bleak. Imagine if there was a drug that meant you're less easily satisfied, who on earth would want that?
> If anything the opposite is far more bleak. Imagine if there was a drug that meant you're less easily satisfied, who on earth would want that?
That sounds like stimulants. You wouldn't be motivated to do things if you were satisfied, so any drugs that motivate people would seem to need to have to have such an effect.
Work also seems more interesting, but my untreated ADHD seems to be getting worse.