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Comment by cj | Hacker News Reader

I started Tirzepatide 3-4 weeks ago. (Mostly as an experiment to understand the hype around GLP's... I don't have diabetes and only very slightly overweight at 20% body fat). Even at the lowest 2.5mg starter dose which you're only allowed to stay on for 1 month:

- Extreme appetite suppression to the point where I've started calorie counting specifically to make sure that I'm eating enough. It's incredibly easy to forget to eat.

- No more feelings of hunger. At all. This is somewhat depressing. Eating is no longer enjoyable and feels like a chore. I woke up hungry for the first time in a while a couple days ago and was excited - jumped out of bed and ran to eat something just for the pure joy of it. I've only felt that a few times in the past few weeks, compared to every day off the drug.

- I completely stopped drinking. Have you ever been to a bar after eating a big meal at a restaurant, and had trouble drinking because you were too full from your meal? That's how I feel all the time. 1 or 2 beers and it becomes uncomfortable to have anymore.

- Normally I go grocery shopping and within 3-4 days, all the "good stuff" (snacks) I bought are eaten. Now, since I stopped snacking and eating much less, groceries simply last way longer. <-- $$ saved in groceries significantly offsets the monthly price of the medication

- My morning starbucks routine has changed from 2 food items to just 1, which alone saves me $200/mo (sorry starbucks).

- Haven't noticed anything regarding impulse control outside of food. No anecdata to share on that point...

After a few weeks on the drug, I'm 100% convinced that once this drug is widely available and cheap... being overweight will be a choice (choosing not to take the drug).

The most important aspect of the drug that makes it work so well is it forces you to change your habits, no will power required. It also punishes you for bad eating habits. (That late night trip to McDonalds will have you feeling like shit the next day).

I'm the kind of person that used to be able to order just about anything on a restaurant menu and clean my plate completely. Now I simply can't do that. It's actually kind of embarrassing being at a restaurant with friends and being completely uninterested in the food.

View on HN

I’m not going to lie all this sounds like heaven to me.

I absolutely hate the way my appetite works. I have a genuine dysfunction with food. It goes back as far as I can remember. My cravings never stop, even after being satiated. It’s an endless cycle of weight gain then loss then gain as my willpower fluctuates for a variety of reasons.

My insurance only recently started to cover these weight loss drugs, and I have been looking into them over the last month because I think I’m an ideal candidate for it.

If it gives this kind of control over cravings and appetite I’m really looking forward to how this can genuinely make my life better

I'm a few months into this drug as well, and I have to say, it doesn't offer control. What it offers is a lack of cravings & appetite. That is different, remarkably so.

Control would mean I might still feel hungry. Ever. Or that I could decide to eat heavily at one meal, but I don't and as long as I take the drugs, I won't. That doesn't feel like control, it feels like I've had something removed. I guess it's a matter of perspective?

I don't know if its a common sentiment but this drug treatment is the hardest thing I've ever done for my health. I'm not sure I'll be able to continue though. It's like I've robbed myself of the one joy I had left and now I have none. Tread carefully.

The difference here may simply be in how our mental health relates to food.

It sounds to me like it brings you enjoyment you miss. I respect that.

Food for me isn’t that. The lack of cravings and appetite means I would be firmly in the drivers seat with it. It means I can eat exactly the amount I’m suppose to and not feel like I must have more

Note that if you're doing this treatment at home (aka bought a vial and a syringe off the Internet and are injecting yourself), you can simply give yourself slightly less next injection. It's not a binary "hunger (y/n)" but more of a spectrum. (anecdotally)

Stop moving up the dosage so fast.

I'm under the care of a physician, and my dose is fine, and managed by him, thanks :)

Then I'd encourage raising these concerns with your physician then and asking for a lower dose.

>> [it's] the hardest thing I've ever done for my health ... I've robbed myself of the one joy I had left and now I have none

> [but] my dose is fine [because] I'm under the care of a physician

Get a second medical opinion from a doctor experienced with prescribing these drugs.

I don’t understand what’s missing. What was the joy?

For me, hunger is misery, and so is feeling over-full. I’d do anything to take that away (well, short of sacrificing my financial security to pay the market rate for the drug.)

Try reading Gary Taubes and seriously monitoring your carb intake

Your body has 2 separate engines that work completely differently

I'm a major snacker in my 40s, have been most of my adult life. When I don't have my daughter I would fill myself up with cookies, cereal, and chocolate candy. I've been a few months off of all of that shit, accidentally didn't really plan it, I just haven't had any cravings whatsoever. I'm sure it could come back easily but it's not here and I don't miss it. I've lost a lot of fat. I'm not just eating fruit and vegetables, but I'm finding meals alone are enough.

I've been on them for over a year now. I was 320lbs at my peak. I'm down to 247 as of today. I have about another 27 pounds to lose, and then I think I'll be where my doctor wants me.

Here's my experience (n=1):

* Zepbound is better than Wegovy. Wegovy has more side effects than Zepbound. Also the Zepbound pen is better than Wegovy.

* If you're worried about needles, don't be. The injection feels more like a rubber band snapping at the skin. And you'll get used to it.

* I typically have moody days maybe 2 or 3 days after I inject. I attribute that to blood sugar changes.

* Food tastes differently to me now. Food I used to really like can sometimes now just be okay. I don't like french fries so much anymore like I used to (they're good, but not what I remember). The huge bowl of chips I got from the Mexican restaurants don't taste as good anymore. Potatoes aren't really as attractive anymore. I prefer protein.

* I had constipation, which is a side effect. There was a stool softener I took from costco that helped. Eventually that went away.

* I got a bike for exercise. It's nice in that I feel like I actually go places rather than sitting on a Peloton. I also get fresh air. I had to find something I wanted to do, and I hate walking frankly.

* As I lost weight my alcohol tolerance dropped, but it's to be expected but still surprising when one beer hits you harder than it used to.

Maybe some tips:

* Nausea might a be a side effect, more so with Wegovy than Zepbound according to my doctor. So I guess plan to take it easy if you can.

* Your relationship with food will change, so be prepared mentally for that. Food used to make you happy maybe, and now it won't. So figure out what activities and interests that make you happy which don't involve food.

* Sugar is the one thing that can still ruin your progress. So be careful with desserts/candies/sweets/sugared sodas/etc.

* There's some debate about whether diet sodas spike your insulin levels or not. I would recommend going to black coffee to get your caffeine if you haven't already, and black coffee will also help to stimulate your bowels as well. That said, diet sodas are still better than sugared sodas.

Don’t waste your time with insurance. Just go to one of the consumer facing companies that compound them directly.

I’ve seen cases where these sites are 5x cheaper than insurance

FDA has determined the shortages of the non-compounded versions has been resolved (of zepbound/tizepatide in October 2024, and wegovy/semaglutide last week): https://www.fda.gov/drugs/drug-safety-and-availability/fda-c...

So compounders can no longer legally sell tirzepatide and will soon (April-May) be unable to legally sell semaglutide.

That said, the lowest doses direct from Lilly without insurance are $350-500/mo. And if you can do math, you can pay for a higher dose and spread it out over time to achieve a lower average price.

I've heard similar accounts and it sounds pretty wild. I'm not overweight and don't take anything but I do enjoy food. It would be horrible to me to lose the enjoyment of such a primal pleasure. If the choice is between being overweight and giving up the pleasure of eating altogether, I can imagine plenty of gourmands who would rather carry the extra weight for the physical and social pleasures of food. I've heard anecdotal reports of people losing their enjoyment of food permanently, even when discontinuing the drug. Canot confirm but that would be a high cost to pay, imho.

Counter-anecdote.

I have not lost my appreciation for good food, I just eat less of it. I used to be unable to leave any food on my plate regardless of how good or bad it was, now I’m perfectly happy to leave something uneaten if it isn’t to my taste.

Same, I'm on one of them and I still love and enjoy eating and am perfectly capable of eating my beloved junk food. I'm just highly likely to feel done after a few bites instead of... dozens and dozens of bites.

Losing the pleasure of food was one of my main concerns starting it, and it hasn't been an issue whatsoever.

Meanwhile, I'm back down to my healthy weight range, which I haven't seen since 2021, which was about the third time I'd been at that weight and then ballooned up. I was just about at the top of that range after two months, down about 30 pounds, and it took no effort whatsoever.

I feel amazing. Muscle mass is also doing fine, and I'm well into middle age so any protective properties of youth are largely gone, still having no problems there.

Same for me, I don't recognise those symptoms (loss of taste, loss of impulses). My understanding is that all it does it to replicate the signal the stomach sends when it is full, and so you just feel full / a bit burpy, even on an empty stomach. But you do enjoy the same taste than before the drug.

That being said side effects vary and lots of people mention it gives them nausea. I can easily imagine how that would interfere with taste.

I actually appreciate food far more now, because I am no longer worried that I have to consume “enough” food. A small amount is just as satisfying. A large amount makes me ill, and you only make that mistake once.

I resonate with your comment about appetite loss. It is surprising how much it has affected my happiness, to have this few times a day pleasure taken away.

A month ago I suffered through a norovirus infection, the first time for me. In three days I lost six pounds (my BMI is 21.2 now). At first I wasn't surprised or worried -- after all, I had emptied out my digestive tract and was dehydrated. But a month has gone by and my appetite has been AWOL. I've lost another pound (5'11" @ 152 lbs). I have an appointment next week with my doctor's PA to see if something else is going on.

The taste of food is the same, but the craving is lacking. When I eat, my guts are telling my brain it is time to stop eating, as if I had eaten a pound of mashed potatoes only an hour ago.

Maybe, Norovirus affected GIP and GLP-1 hormones. This could be a new research avenue for weight loss. GIP and GLP-1 are product of the research about the Gila monster lizard, which eats three or four times a year and survives.

I'm curious -- do you have any brain fog? Are you able to exercise? When you exercise, do you wind up eating more, i.e. the caloric amount that you exercised?

I've never had any psychological difficulty with losing weight. I don't care if I'm hungry.

But what happens when I eat less and lose weight is that I have trouble concentrating. The glucose my brain needs just isn't there. And if I do physical activity, forget about it -- my blood sugar is going to my muscles and I'm unproductive for hours afterwards as I just can't think. Also, if I go to the gym, my muscles take a week to recover instead of a couple of days, because they're just not getting the glucose they need to repair themselves.

I don't hear any of these complaints from GLP users though, which baffles me. Not eating enough affects us in lots of ways besides just being hungry. How has it been for you?

No brain fog. I walk at a very brisk pace ~6 miles a day. My calories are far less than before I started. I have to be very careful to have enough protein. When I exert myself, the recovery period is the same time as before.

Do you have any idea of how many calories you eat per day?

I get so confused because the small amounts of food that people talk about eating on GLP, don't seem like enough to sustain themselves long-term.

Are they exaggerating? Or do they talk about not eating dinner, but that's because they had 1,700 calorie lunch at the burger place? Or is that just during weight loss, and then once a target weight is hit, they're eating like a normal (healthy-weight) person again?

I just genuinely don't understand how people are surviving with the diets they describe.

Yes, I calorie track around 1900 calories average. Maybe up to 2000?

They are probably losing muscle mass!

Oh, OK. So depending on your height, that sounds fine.

So you're still eating plenty, but the point is that you no longer have any desire to over-eat?

And so at a restaurant you still order and eat, but the food just doesn't mean "enjoyment" the way it used to?

That makes a lot more sense then. If food becomes more about removing a negative feeling of discomfort, than a positive feeling of deliciousness, right then overeating would never make any sense.

Thanks!

Yeah, I am 6’2 and broad chested etc - I am consistently losing like 2 pounds a week, give or take. If I am less active like due to illness, that slows down. I think any faster than that, and I’d be worried about crashing back to my old weight or other side effects.

I went out to eat today, and enjoyed my food. I didn’t order a big burger, but a smaller sandwich. I had a bite of an appetizer, but not more than a bite. Still super enjoyable, but it might be even better now because I don’t feel like a fat pig afterwards due to reasonable portion size.

I am food motivated like a dog, for whatever that’s worth.

Good food still tastes good. You're just less hungry.

> I just genuinely don't understand how people are surviving with the diets they describe.

Because obese folks have stored energy reserves. The body is really good at adapting and using them.

I was attempting to be at a 1k/day calorie deficit during my peak weight loss phase. I typically met or beat this target, usually eating around 1200-1600 calories/day plus a lot of walking - 25k steps/day minimum as an absolute non-negotiable. I'd check my step counter before bed, and put pants back on and go for a "midnight" walk if I was under my count for the day.

The first few weeks were quite hard, but it was pretty smooth sailing after that. Lots of naps. After that I was tired some days, but not overly so. I peaked at about 30lbs/mo weight loss for ~3 months, then tapered off to 5-10lbs/mo for my final 30ish I had to lose.

I don't really suggest anyone else attempt to "crash" their program like I did - but it's how my brain operates. I need immediate and obvious results, and those turn into a feedback loop for me. Being a bit more tired each day was perfectly acceptable for the goals being achieved.

That said - I wish I had started resistance training when I started my dieting program. I took it up at the very end of my weight loss, and it took me about 9mo to get back to roughly the same lean muscle mass as I had before I lost weight. I'm still working on min/maxing body comp about 18mo later.

The best weight loss program is the one that works for you. Pretty much full stop. It's going to be highly individualized. Some folks will do much better with a small deficit for a few years, but I know from experience that would never work for me.

I think a lot of the stuff you see on-line about "forgetting to eat dinner" is exaggerated and folks starting off on the drugs being amazed at it. Very few people will post a "well, I'm a bit less hungry" type of result. Everyone I know on them eventually became somewhat habituated to this sort of effect, but everyone is highly different. For me, I considered Tirzepatide a performance enhancing drug for my diet. I still went to bed hungry most nights - it was just far easier to chain together days and weeks of doing so on the drug vs. off. It still took a lot of willpower and habit building for me to pull it off at that level.

> Do you have any idea of how many calories you eat per day?

My baseline was in the ballpark of 3000-4000 cal/day. I'm losing about 5 lb/month, or 1.25 lb/week; assuming it's all fat, that's a 4400 cal/week deficit or ~625/day. 600 cal a day less is kind of a lot! Some people starting fatter than I was take bigger doses and have bigger deficits.

> Are they exaggerating?

In my experience: I'm not hungry for breakfast at all. Lunch: I try to have it, definitely have it if I exercised. (But if I didn't exercise it's pretty easy to just ignore hunger signals and eat my first meal at dinner.) Dinner is like, smaller than it was when I wasn't on the drugs. And then some post-dinner snacking.

I'm on the low end of the Rx dose range (2.5-15mg/week); on a higher dose, eating even less is plausible.

> Or do they talk about not eating dinner, but that's because they had 1,700 calorie lunch at the burger place?

1700 cal meals are mostly out of the question for me on these drugs. Your gastric emptying is slowed down, so you just can't house big meals in the same way.

> Or is that just during weight loss, and then once a target weight is hit, they're eating like a normal (healthy-weight) person again?

Yes, I think this is a big piece of it. To actually lose weight, you need to eat less than the sustainable steady state.

> But what happens when I eat less and lose weight is that I have trouble concentrating. The glucose my brain needs just isn't there.

This is crazy, I have the completely opposite effect. On keto + calorie restriction I feel much more alert and sharp.

Well yeah in ketosis your brain is running on a different energy source

It's because people are different, sometimes on a genetic level. What works well for one person does not work well at all for another, like the parent commenter, I do not work well without carbs. Keto puts me in a low-energy, semi-depressed state, while eating +80% of my calories as starch led me to lose about 15lbs of fat and now I'm the lowest body fat % I've ever been in my adult and teen life and my HOMA-IR went from 3 to 1.6!!!!

And my genetics also showed this to be the case too!

Can you elaborate on the genetics part? What were the relevant SNPs?

It got a bit complicated; it was a long research project, and it led to me starting my current company, Patchwork. Currently, it's at a few hundred. https://www.patchworkfood.com

No brain fog, but in my experience it does impact exercise (similar to any other caloric deficit). Both maximal efforts (e.g., heavy barbell squats) and endurance (hours on the bike).

Your muscle repair would come primarily from protein. I used to train quite intensely and this protocol worked for me (timings matter):

- 45 mins before workout: small bowl of oatmeal with milk

- 30-0 mins before workout start: 1 liter of water pre-hydration

- During workout: 1/2 liter of water per half hour of intense cardio training, less so for resistance

- Straight after workout: double black espresso coffee (high caffeine)

- Hit sauna for extensive slow cool-down, drinking one sports drink (sugars and electrolytes)

- hour later: full meal of mainly lean protein

Never had issues with muscle pains or "fog".

If you go really deep beyond your usual sustain, feeling physically exhausted and needing rest afterwards is normal. Eating your way through it is not the way to go.

> Your muscle repair would come primarily from protein.

This is a common misconception.

Yes, muscles are made from protein, and so you need additional protein to provide new "building blocks".

But the process of muscle repair uses a far greater amount of glucose to actually do the work of assembly. Estimates are generally that you need something like 10x as many calories from carbs/fats to build muscle, compared to the actual protein required.

So no -- muscle repair actually comes primarily from glucose, if you're measuring calories. But the point is that you need both. If you eat plenty of protein but your blood sugar is low, the muscle growth/repair will be extremely slow, or just not happen at all.

Also, your protocol is entirely about the workout. I'm talking about the 48h afterwards, when the growth actually occurs in response to the stresses incurred during the workout.

Awesome stuff. Envious, here (NL) its impossible to get a prescription.

For an alternative approach for comparison: My wife and I eat low carb and fast every other day for a year now. Around the 2nd month mark we got the exactly same outcome: food became a chore. We sometimes dont eat for 2-3 days when travelling or busy. I dont remember feeling hungry in about a year. We do sports - I sure have less peak power, but can sustain moderate efforts for longer (I use a power meter and Hr strap - my vo2max dropped). I feel significantly sharper mentally and managed to learn a new language (Dutch, from zero to B2) in a year - while working a cto job. Not eating easily gives 3hr extra a day, incl. what I get from waking up early.

Saves us a ton on groceries and eating out. The only thing we do watch out is carbs - I can eat a kebab or two tacos but dont eat any sweets, eat bread or drink beer/soda. Weight stabilized at my high school level. Not sure if I can recommend it as it is a bit tricky to practice, especially while having a job that requires routine socializing, but - it does work. The only really difficult thing is to start and endure the first two weeks or so.

That sounds very intriguing, are you a bit concerned about the dropping vo2max ? Do you eat a lot more meat than before?

No, I eat a lot less in general and a whole lot of veggies.

I followed the same routine 4 years ago, then I stopped and when I started eating carbs my vo2max recovered overnight. I think one cant have it all - either you run on stored energy which caps the power to weight ratio - or on readily available glucose and glycogen. Its fine, I am not an athlete, I do sports to feel good. I dont see an impact on raw strength - just on anaerobic performance.

Do you mean aerobic performance in the last sentence?

Anaerobic - i feel more or less normal while under aerobic load, and i can sustain significantly less anaerobic load - i used to be able to maintain 1600W for about 30 seconds (equivalent to a sprint to a finish line at pro-cyclist level). I can barely touch 1000W while on fast/low carb diet. I did a few experiments, and after carb loading I get an immediate increase in anaerobic perf.

> being overweight will be a choice

Not everyone can take these drugs. Some people will have severe side effects. It's very common to have nausea, vomiting, etc., and some people will experience these frequently enough that the prescribing doctor will rescind the prescription.

gastroparesis is a real side effect two, it’s where the food in your digestive tract stops moving. As in 30% of food is present after 4 hours

The rate is over 1% which isn’t a lot nor is it nothing https://jamanetwork.com/journals/jama/fullarticle/2810542

It looks like it's mostly caused by having too high doses of GLP-1 too soon.

I’m not about the root cause. I’m on a GLP-1 and while doing a premortem on my medication I saw that this, vomiting, and burps were common.

I've been using GLP-1 agonists since before Ozempic, and by now I have no side effects from them.

My doctor said that she now titrates the dose up slower than the recommended monthly increments and the side effects are less frequent.

Another problem is that GLP-1 drugs seem to synergize with other drugs that can cause GI issues.

I tried, I got some results but it meant that my entire body’s digestive system felt like it stopped working. Constipation, nausea at the drop of a hat, finding I’d have to take a fast acting prescription anti nausea multiple times a day. I’m not that overweight, and I felt like my body was getting far less healthy and like I was starving myself. This is on the lowest starter dose, too! It just… yeah, it works as I’d expect an extreme appetite suppressant would.

Are these the same effects that folks would get if they stopped eating cold turkey?

Would Zofran throughout the day help with the side effects until the body adjusted?

That was my hope, and I gave it a shot for a few months. I seem to be an outlier though!

Thanks for sharing your experience :)

Those side effects are from injecting weekly doses, right?

I'm curious if daily oral doses which are smaller will solve a bunch of these problems at once, while also mitigating the supply-chain problems.

The oral semaglutide (sublingual dissolving) is like 10% as effective as the injected version. But it presumably could be given in higher doses to counteract that. I'd be shocked if the manufacturers aren't working on a more effective non-injectable version.

My wife was on daily doses and it made no difference. She's now having long-term problems, over a year after getting off of it.

What side effects/problems are you referring to?

Non-stop nausea and uncontrollable vomiting every day since. She's been to numerous doctors and even got her stomach scoped.

https://time.com/7130456/ozempic-side-effects-wegovy-mounjar...

That sounds awful :( sorry yall are going through that.

FWIW, you can inject half as much twice a week, or whatever schedule works for you. I do it every 3-4 days.

This was me. I’ve been on them for four years and actually gained fifty pounds

The drug keeps me from binge eating, which is huge, but if I take enough to actually lose weight then I have weekly bouts of food poisoning because the sugars in my gut start to ferment. An entire day sitting on the toilet while holding a bucket because it’s coming out both ends.

> My morning starbucks routine has changed from 2 food items to just 1, which alone saves me $200/mo (sorry starbucks).

Starbucks food is especially calorie dense. I realized this when I lost a bunch of weight in 2018 and I noticed the calorie counts on the printed cards that some stores have. Even for junk food, Starbucks junk food is more calorific than average for the same items.

I started to consider that for a typical customer's consumption, McDonald's might actually be healthier than Starbucks. Which totally goes against the image people have of both places.

People think if they are "going for coffee", it's better for you than having a milkshake and following it with candy. But it's essentially what they're doing.

"Starbucks's greatest trick was convincing grown-ups it was OK to have a milkshake for breakfast."

(I heard this somewhere on the internet, about the Frappucino.)

I am 8 months in, you do develop a tolerance over time to the drug (and why you need to increase the dosage progressively). I have gone up slower than the prescibed steps but still, this drug is to help doing diets, I don't think it would work as a long term medication. And as far as I can tell, when you get off the drug or have become tolerant to the current dosage, it is easy to gain back some weight if you are not careful. So the point being I don't think it will suppress completely obesity, but it will certainly help people make a time limited effort to go down to a lower weight.

Some doctor advised a protocol: stay on GLP-1 for 3 months, then take metformin for a month or two; then repeat the cycle. I have to dig out the source for this.

I’ve been on it for over 2 years now. Yes you plateau, and if you go off of it (as I had periodically), you will regain weight. Hoping my weight loss resumes now that I’m back to the maximum dosage for a few weeks. As it’s 5pm and I just ate for the first time today, I can confidently confirm that my appetite is well suppressed.

"I don't think it would work as a long term medication"

It seems like there is a lot of disagreement on this very basic point. Surely there must be data from the decade or so it was prescribed for diabetes.

Interesting, what is the end game then if you need to be on the drug to keep the weight off but you also develop resistance to it over time?

I wonder how the body reacts after being on the drug for years at a time and then you cut it off, are the cravings stronger than before you started the drug?

Doesn't mean you go back all the way up. And I don't know if the resistance wears off if you stop taking it. What I am hoping is to end up in an end state where I can keep the weight within a 5-7kg range and go on the drug for 2-3 months once a year to go back to the bottom of the range.

I think the craving is primarily a function of how much your stomach expects food, ie the more food the more craving, but also you can get it used to a lower regime. And to external factors like stress, tiredness, cold, etc.

Yes well your PCP / pharmacist should not have prescribed you an appetite suppressant when you have below average body fat %. The effects are very worth it for people weighing them against heart disease and mobility issues. It's not a Faustian bargain, it's all right on the tin. When you stop taking it the effects go away. If you want to be indulgent and it fits your lifestyle you can reversibly make that decision. The power to make that decision is difficult to overstate.

Why is it only appropriate for people with heart disease / mobility issues but not for someone who is merely overweight? This feels like finger-wagging for the sake of finger-wagging.

It isn't. 20% body fat is 6% below average. That isn't "merely overweight", it's likely underweight. No, I don't think underweight people should take appetite suppressants and I don't think that qualifies as a hot take. I think anyone who is medically overweight (which is a very modest BMI qualifier for anyone with any amount of muscle) should have the choice. Many US medical systems and insurers agree, which is a good place to be.

>it's likely underweight.

The only way this can possibly be correct is if you think that the "correct" weight is whatever the population average happens to be which is just...wild to me.

If we assume commenter is male (a statistical likelihood), then 20% is the high end of normal, and could very safely be halved. In the less likely case that they are female, then it is right in the middle of the normal range, and could safely be reduced by 5-10% at least.

> The only way this can possibly be correct is if you think that the "correct" weight is whatever the population average happens to be which is just...wild to me.

The medical definition of overweight is basically if you're some number of standard deviations above the average from whenever they ran the stats, so population average = correct weight seems like as reasonable a standard.

I tried to find corroborating sources and couldn't, so take this for what it's worth, but Claude seems to think the cutoffs are based on epedmiological evidence for health impacts at various BMIs, which, even if that _wasn't_ how it was arrived at, seems like a better option.

What are you smoking? 20% is a perfectly healthy bodyfat number and (for a man) anything down to 15% or so is fine. Sub 10% is when you pretty much need a crazy bodybuilder lifestyle to maintain it. And on the other side, 25% is around the lien where you start facing some minor health risks from excess body fat.

Average is overweight, though.

You're confusing average with good. 15% body fat (for a man) is completely healthy, so as the OP said, he is slightly overweight.

> Yes well your PCP / pharmacist should not have prescribed you an appetite suppressant when you have below average body fat %.

Why do you think this? I agree that people who have associated risk factors should be prioritized, but if there's enough for everyone why wouldn't we give it to anyone who wants it?

Because anorexia exists it would do harm to completely unregulate access to appetite suppressants. Someone should be looking out for people who would willingly wither away.

I don't think anyone is suggesting it should be over the counter? Of course a doctor should monitor you while you are on it. We shouldn't give it to people who would use it to deepen a mental health diagnosis.

Those concerns have nothing to do with the fact that it's ok for people to choose to start or stop medications if they would prefer (supplies allowing).

Putting Ozempic over the counter at a local pharmacy would be more than enough to keep people from wasting away, the same thing they do with asthma medication. In 2025, if you really want something, a dark web tutorial is 30 seconds away. And from what I've heard from a client, Ozempic on the dark web is roughly 5x cheaper.

sure thing, but can you trust it ? There are so many horror stories abroad (like LATAM), that despite the 4x price point, people still buy US-manufactured GLPs instead of going to a foreign market to get the same prescription.

This is being injected directly into your flesh, there cannot be any mistake, or shortcut.

What horror stories?

People who don't need to be chronically medicated should not be. There are always side effects, and we don't even know for sure what the long term risks of these medications are yet.

And crowing about saving $200/mo not buying food at Starbucks, well now Novo Nordisk is getting that.

Toast a bagel at home for $0.50/day instead.

I am not an expert but my impression is semaglutide has been in development since the 90s and in use as a drug for about a decade for people with diabetes. The drug and mechanism are old, the use is new.

I do not agree that people who don't "need" to be chronically medicated should not be. I think you can decide to take whatever you want for your own reasons. I am not going to tell you what you can and and can't take - unless you're like...taking something that makes you destructive or generate externalities or whatever. But this seems like the opposite?

Lots of questions here around profit and the awful medical system in the US, but on a basic level I think people should be able to do what they prefer and is safe.

I was giving advice, not proposing a prohibition against doing what you want to do. It's your body, and your health.

> People who don't need to be chronically medicated should not be.

If they're like typical westerners, they already self-medicate with coffee every day, with alcohol occasionally, and a big fraction of them (though much less than couple decades ago) also treat themselves with tobacco smoke - and ironically, weight loss is one of the few benefits some people actually use to defend their smoking.

Do they need all that medication? Well, it's socially unfavorable to say so wrt. alcohol, but ask any of the daily coffee drinkers whether they need their morning coffee...

Caffeine withdrawal takes two weeks.

That "medication" has been used for millenia and its side effects are well understood by now. Not so much with these relatively new drugs.

The consequences of tobacco are so well known and so negative that they are legally mandated to be graphically depicted on every cigarette packet around here, and the main reason they are not banned is the observed impossibility that undid Prohibition in the USA.

So, sure, we don't know the long term risks of semaglutide ("just" 30 years or so) — but I say let people try it if they want, we let them use things we explicitly know to be dangerous, so why should we stand in the way of something that only might be eventually?

what kind of crap bagels are you buying for 50 cents?

What do you think Starbucks pays for theirs?

I buy Thomas Everything bagels at the supermarket, FWIW.

This really just seems like a shit take to me. Everything has side effects, that doesnt mean everything is a net negative. People should be able to weigh the pros and cons of chronic medication and decide if it improves their life.

After using them, I think GLP-1’s will eventually be rebranded as a weight management / weight maintenance drug rather than a weight loss drug in order to appeal to the masses.

It’s a very interesting feeling to feel like you’re in full control of what you eat, not influenced by random cravings or hunger.

In my case I’m planning to only stay on it another month or 2 to drop 10lbs. I can easily see people cycling on/off this drug throughout the year to keep weight in check while removing will power from the equation completely. It’s quite remarkable.

A rebranding to a non-prescription drug will depend on how the prevalence × severity of side effects [0] turns out longer-term. I hope that you are right, but it seems too early to tell.

[0] https://www.sciencedirect.com/science/article/pii/S266736812...

https://www.gov.uk/drug-safety-update/glp-1-receptor-agonist...

"Gastrointestinal side effects" I assume that is code for excessive and frequent evacuation of watery feces.

“common gastrointestinal side-effects of GLP-1RAs treatment (including nausea, vomiting, diarrhoea and constipation) can persist for several days and may affect more than 1 in 10 patients”

For me, nausea only appears when I eat poorly - poor quality, or more than I should. Also increasing a dose can cause a bit of nausea for a few hours.

People seem to handle it very differently, according to my doc. I never had issues while taking Mounjaro or Synjardy (a prescription pill for diabetes management with similar side effects) alone, but the two together meant I could count on a couple of bad days a week.

Sidebar: Mounjaro changed my life. I'd been very diabetic (300 units of insulin a day) for years on end. Taking that much insulin, my normally large frame got very large indeed. A couple of months into the Mounjaro and I was off insulin; a year into it and I was down 75 lbs and healthier than I'd been in 20 years.

It’s actually the opposite. GLP-1s slow down the digestive tract, so my shits are far more well formed than before. This isn’t like olestra, where excess fat caused diarrhea.

Ok I'd been considering it already, but now I'm sold. I have the transit time of a canid.

It’s wild. I’ve never experienced burping food and tasting what I ate earlier, food just kinda rolls right through. Now, I get to really enjoy it a second time.

Who needs an appetite suppressant when they have comments like these?

Let me know when you need a little appetite adjustment. Free of charge!

fwiw tirzepatide (likely the GIP component) cleared up my lifelong IBS within days of my first dose.

I consider it a likely lifelong medication now simply due to that night and day difference to my life. It’s extremely rare I have a day where I need to be within 5 minutes of a restroom now.

My primary care doctor mentioned this might be a side effect when I first started, and she ended up being more correct than even she expected to be.

In this sense, I see adoption among some people as akin to nootropics or attention management drugs like modafinil. A way to have more control over your own mind. Interesting times, I guess, but caveat emptor.

They might be branded that way, but that's not what they are. They have dramatic effects on the metabolic pathway and insulin response that need to be carefully considered if you're not actually diabetic.

I recommend that you listen to the most recent Peter Attia podcast, which is a 2+ hour interview with Ralph DeFronzo (diabetes expert) where he goes deep into the effects of GLP-1 agonists on insulin response and other metabolic pathways. I came away with the impression that we're being too casual with how these drugs are being used -- if you're overweight these impacts are probably all for the good, but if you're not, it's more questionable.

https://peterattiamd.com/ralphdefronzo/

I’ll have to rewatch that video. Saw it a couple days ago and walked away with the opposite take. DeFronzo spent a whole lot of time heavily praising the generation of drugs (including the next generation in phase 2 trials)

If there’s a specific part you remember talking about the negatives I’d be interested to hear.

I legitimately have a difficult time finding anything negative when researching the drug, other than tolerable side effects like GI upset.

He's praising them for people with clear metabolic syndrome, and I'm reading between the lines as someone with prior knowledge. As a simple example, while it's probably good to inhibit gluconeogenesis in people with elevated A1c, doing so in a healthy person could lead to hypoglycemia.

I don't have a list of exact timestamps, but there are multiple places where he discusses the impacts of the GLP-1 agonists (of various generations) on insulin signaling, glucose transport etc., and the conversation is generally complex, nuanced, and wide-ranging. We don't understand everything these drugs are doing, but they're clearly banging around a complicated metabolic/hormonal system with a big, blunt hammer.

Specific part of the interview that talks about GLP-1 safety with DeFronzo and Attia: https://www.youtube.com/watch?v=QGIFdakceHM

Yeeeeah, he says that "they're quite safe", but it's in the context of a wider conversation focused on people with metabolic syndrome. I wouldn't be eager to extrapolate from that comment to "let's put this in the water supply" (exaggerating for the sake of argument).

I assume GP isn't a woman, why do you think 20% is normal for men. The point is that there are no side effects and there is no reason to stop taking it, especially if it saves him money.

Are you just using average as weasel words here? I get my best pump and generally have the best workout sessions at ~10-12%, which is easily maintainable for me, but definitely not for most people, having a drug that makes it effortless for most people is a GOOD thing. People shouldn't have to suffer to get to <15% if they aren't born with good genetics?

And what about strength athletes who want to build up a large runway? Now literally all of them can get down to ~7% no problem, and have no problems on the way up either.

You shouldn't have to ask permission from a PCP / pharmacist in the first place. Who are you to decide whether side effects are worth it for anybody but yourself?

> when you have below average body fat %

I can't speak to their choice of taking the drug, but it's wild how warped people's perceptions are now of what constitutes "healthy" and "fat" thanks to the obesity epidemic. People remark on how George Costanza on Seinfeld was once considered fat (because he was), or how Homer's scale-tipping 300 lbs. in the King-Size Homer episode of The Simpsons was considered comically obese (because it was). Never mind the fact that people almost always underestimate how fat they actually are and are almost always disappointed by their DEXA scans. Even if the OP's estimate is correct that they're just a little north of 20% BF (as a man), they're still overweight, and specifically overfat, and probably look soft and doughy.

It's weird that I've never been overweight and you describe basically how I normally feel.

I've never felt hungry in the morning. I've never eaten a lot. When I was younger, I often forced myself to eat more, because I felt bad about how I wasn't "big enough" (which feels silly now as a proper adult).

Impulse buying food and snacking is something I only do if I haven't eaten for a long time, i.e. if I'm actually very hungry.

If I go out drinking, I also make a point not to eat very much before or during the drinking, because otherwise I just feel sick after like one beer.

I used to feel that way in my 20s. Things changed a lot when I hit 40.

I've been on tirzepatide for 8 weeks (2.5mg then 5mg) and have a very similar conclusion as you. I started off at 160kg 8 weeks ago and now I'm down to 145kg. No other change in my lifestyle except eating radically less. Two 500-calorie-ish meals a day and some fruit as a snack, that's about it.

For decades I've struggled with diets but tirzepatide is the only thing that's made me stick with it. Will power alone wasn't enough, but with tirzepatide I'm very confident I'll get down to a under 100kg for the first time since I was a teenager, within a few months.

You lost 35kg in 2 months? That's insane. Any issues with loose skin so far?

160 - 145 = 15kg

> The most important aspect of the drug that makes it work so well is it forces you to change your habits, no will power required. It also punishes you for bad eating habits. (That late night trip to McDonalds will have you feeling like shit the next day).

But the late night trip to McD's always makes you feel like shit the next day, it's just that we then forget and do it again. (Same with drinking).

The best description of drinking I've heard is, "you're stealing joy from tomorrow for today."

> Extreme appetite suppression to the point where I've started calorie counting specifically to make sure that I'm eating enough. It's incredibly easy to forget to eat.

This is the largest of several reasons I hesitate to try it for myself. I am a very big guy (I would be about 184lbs if I had 0% bodyfat at my current musculature level). From the experiences I hear, I would not only struggle to have enough energy to do any kind of rigorous exercise, but struggle to consume the amount of protein I require to even maintain my current muscle mass.

I do have issues with overeating and the prospect of a drug that prevents me from consuming too many calories is attractive, but the side effects sound counterintuitive to any kind of natural fitness.

I’m somewhat the same. I need to be active for other health reasons (physical therapy, etc) and not eating enough saps my ability to push forward physically.

I’ve been hyper aware of the muscle loss caveats and I think it’s the most important thing to know when starting the drug.

You really need to prioritize protein intake and make sure your calorie deficit isn’t extreme.

Losing too much weight too quickly, with or without the help of a drug, can be very unhealthy.

I drink 4 protein shakes a day (160g total) in addition to regular food. If it weren’t for the protein shakes I definitely would be protein deficient.

You’re 100% spot on with decreased energy at the gym. I’ve had to pull back 4x weekly cardio to 1-2x weekly. Then again, anyone who’s in a calorie deficit has lower energy. It’s not a unique phenomenon of the drug, just a side effect of weight loss.

> Then again, anyone who’s in a calorie deficit has lower energy.

Presumably if you're trying to lose weight, you have energy to burn you carry around with you. A calorie deficit doesn't imply lack of calories to burn. Presumably you're trying to trigger ketogenesis.

Granted, this is a lot less easy to access than simply eating simple carbs right before a workout and likely a lot less comfortable.

> Presumably you're trying to trigger ketogenesis.

Only if you're actually on a keto diet; most weight loss routines run a calorie deficit without triggering ketogenesis.

Also there's this whole thing about set points - you probably got to your weight somehow, and if it wasn't through consistently making stupid choices over many years, chances are this is what the body learned to consider an equilibrium state. Which means that, if you start running a calorie deficit, it's going to fight you every step of the way. It will happily scale down performance to conserve energy instead of burning the accumulated fat, so you'll just be slow and groggy but not lose weight. There's been reported cases where people got mental illness-level obsessive thoughts about food, which appeared when they were hungry, and stopped when they ate enough.

The degree of this problem varies between people, but it's generally not that easy to effectively lose weight, and some people simply lost the genetic/environmental lottery on this.

> The degree of this problem varies between people, but it's generally not that easy to effectively lose weight, and some people simply lost the genetic/environmental lottery on this.

Yea, I think your eating and food habits you learn as a child and teenager tend to shape you for life. I was malnourished as a child (I was considered a picky eater) but as an adult I've found it quite easy to keep within the caloric bounds a doctor told me to keep to. One thing I've noticed is that hunger just doesn't bother me the way it does with people who struggle to lose weight or with binge eating—mostly a pain in the ass (I need to remind and force myself to eat), but occasionally something I'm grateful for as I watch the people around me struggle on an existential level with their cravings and bodies.

I also don't have a sweet tooth, and I put that on not being allowed sweets as a child except under very exceptional circumstances. I'm also a (thankfully recovering) alcoholic, so don't mistake this for being generally good at avoiding cravings.

> Also there's this whole thing about set points - you probably got to your weight somehow, and if it wasn't through consistently making stupid choices over many years, chances are this is what the body learned to consider an equilibrium state.

The idea of set points is controversial and not necessarily the accepted scientific consensus.

> Losing too much weight too quickly, with or without the help of a drug, can be very unhealthy.

Is there evidence to back this up? It sounds reasonable, especially without a limit on "too quickly" but (anecdata incoming) I'm curious because:

   - When I first tried a low-carb diet (for non-weight reasons) I lost about thirty pounds in under three months without really trying, and hit something like 12% bodyfat
   - When I started intermittent fasting (mostly unrelated to weight) I again lost about thirty pounds, this time in a little over three months, and probably ended up around 15% bodyfat
   - Since then I found that neither low-carb nor intermittent fasting had a significant effect on my weight, so:
   - When my doctor suggested I lose some weight I pretty forcibly calorie restricted, and lost about thirty pounds over four months (only down to about 20-something % that time)
   - And just recently, for cholesterol, I've done it again and lost 25 pounds so far in something under three months.

...and as far as I know I haven't suffered any ill effects. I have a concept 2 rowing machine, and I just rowed my slowest 10K ever :-/ but I did row a 10K, and I am in significant calorie deficit, and I probably have lost a fair bit of muscle along with fat, and I have been away from the rower for several months, so all up ¯\_(ツ)_/¯

All of which to ask, what evidence do you have, and what's "too quickly"?

The issues with "too quickly" are:

1. the loss of muscle mass

2. low energy

3. unnecessary suffering

4. high fatigue

4.1. inability to maintain the low calorie diet for long enough

4.2. relapse; jojo-dieting.

1, 4.1 and 4.2 are the biggest problems.

1. I can't speak to that, no analysis here and the time frame (the low carb thing was back around 2008) is too long for meaningful comparison. 2. Maybe? For normal things, not really, but when I try to row for an hour I feel it. I definitely get cold more easily. 3. I'm not built that way. The low carb thing was completely annoyance-free. As I said, the goal there wasn't weight loss, but raising my HDL; the weight literally came off by accident. Intermittent fasting doesn't bother me at all. Calorie restriction, which I generally do by A. going longer without food -- up to 2+ days; and B. eating less/less carb-rich/processed foods; can be somewhat unpleasant if I push it too hard, but I generally don't. Some days I'm feeling it (in a good way) so I go longer without food, some days I'm not, and I don't sweat which is which much. 4. Generally not a factor for me. 4.1. Definitely not a factor. Two times like I said, weight loss wasn't really the goal, so not relevant; and two times I hit the goal I set (last time), or went further (this time). 4.2 Doesn't really apply, since I've never been visibly overweight? Like, my waist has never been close to half my height. I'm tall, so the large numbers aren't as much of a factor. Regaining weight has never happened to me faster than about 10 pounds/year (just a guesstimate).

The interesting thing will be once I stop losing weight and start rowing again seriously, can I get back to a reasonable performance level. Fingers crossed...

I was answering a general question, not talking about you/diet specifically.

It's generally recommended to:

- do heavy resistance training

- losing fat at the rate of 0.5-1% of a body weight a week

- do it for 8-12 weeks

- (critical) after which to have a maintenance phase with a duration of 2/3-1 length of the dieting phase

- after that can do another dieting phase again.

- repeat as many times as needed.

- if wishes to build muscle/bulk, should do it 4 times slower than dieting. So 250g-1kg weight gain a month.

> I was answering a general question, not talking about you/diet specifically.

Sure, I get that, and I responded in the context of my original "I'm going to throw out anecdata" note. In that spirit:

I've generally gone longer than 8-12 weeks, but not by much -- longest is probably 16 weeks?

I've definitely lost more than 1% per week. I don't graph it, but I think I'm hovering in the 1% - 1.5% range.

I'm curious about the maintenance phase and strength aspects -- I'm not interested in bulk, just strength.

Anecdotally (but in line with what I read about this), I got gallstones after getting rid of 30 kgs in about 6 months, which is too fast for losing a third of your body weight. Since I had a scan before starting the diet for unrelated reasons, I'm sure they weren't there before.

Yikes, good luck with that. Fortunately nothing like that here.

If it makes you feel better, this class of drugs has been part of bodybuilding cutting stacks for a while now. It makes the process much easier and as long as you're diligent about your shakes, no big deal.

Wild that a drug with no other side effects that we know of besides pre existing pancreas issues can mute a bodybuilder’s hunger on a cut.

I would be interested in reading about that, but it doesn't de facto make me feel any better given my anecdotal experience with bodybuilders watching them take drastic health risks for aesthetics - it just shifts my concern to other points.

You can just take a lower dose, or cease taking the drug. Appetite comes back. It's pretty low risk.

I don't have a published study to back this up, but in my 10 < n < 100 experience, the alcohol suppression effect is limited to occasional-to-moderate drinkers.

Giving a GLP-1 to a heavy drinker/alcoholic results in a skinny alcoholic.

Given that the overwhelming majority of alcohol is consumed by heavy+ drinkers this isn't the gamechanger people think it is.

N = 14 053 for https://jamanetwork.com/journals/jamanetworkopen/fullarticle... , which looked at if GLP-1 RA use was associated with lower incidence and recurrence of alcohol use disorder.

I'm a heavy drinker (1.5 bottles of wine a day -or the equivalent- everyday, for at least 5 years). I started a GLP-1 at 2.5mg two weeks ago after the most recent study was released[1].

In just the two weeks at that low dose it's been quite effective.

In fact the only reason I'm replying to your comment is because instead of being a bottle deep in front of the TV at this point in the evening I got bored after one glass and decided to noddle around on the internets.

Ask any heavy drinker/alcoholic and they will tell you that one doesn't just have 'one' drink and then move on with something else. One is always too much, and never enough. Now it feels like enough.

Happy the share more if you like :)

1. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/...

Does it have any impact on focus or motivation to get work done, do hobbies or recreational activities, engage in human relationships, sex, intellectual curiosity, etc.?

It would be fascinating and almost too good to be true if we found a way to suppress only largely harmful (in our current environment) urges but leave the good ones intact.

Something like that becoming widely available could change the world, and mostly for the better. It would refocus our entire economy on much more constructive pursuits instead of gambling, addiction, and pandering to transient urges.

I've never had any lack of focus or motivation to get anything done since I started Tz.

I did have some energy loss, especially at first, but I assume that was because my body was struggling to cope with a lack of carbs. However, after a couple of weeks that for the most part disappeared.

This sounds like my whole life, I've always been trim and have never understood the joy people get from food. Facinating to see there's a drug that recreates that physiology.

+1 this has been my life experience.

Two years ago I was some 7-8kg beyond my target weight range. I started calorie cutting, and filling myself with salads etc before each meal. Also added some more changes like taking longer times to eat. I used to, and sadly back to it, eat in a flash. Initially it was hard so increased a bit and then a bit and then in a few days it was stabilised at a calorie intake point which was still significantly below my normal need. And in next few days it dropped further. So next 3-4 months when I was watching calories and trying to keep in check - I didn't have to worry about eating less calories, but I had to worry about taking sufficient calories. Because surprisingly I stopped feeling hungary even eating lesser calories.

I am talking about being okay in 900-1000 while my normal need was ~2500 and nutritionist had suggested to target around 2000 for first few weeks then bring it down to 15-1600 and then slowly bring it up near normal as weight settled. But by the end of 2nd week or 3rd I was struggling to finish 900-1000. I used to kinda force eat.

There was no medication involved in any way (not for this purpose; not for anything else).

> Even at the lowest 2.5mg starter dose which you're only allowed to stay on for 1 month...

So they are going to force you onto a higher dose?!

Yes, up to 15 mg. Maintenance levels at 5, 10, and 15. If you cannot tolerate a maintenance level you can still get it, but insurance will not cover it ($1000/mo rather than $15/mo.) This is not an unreasonable situation.

https://www.goodrx.com/zepbound/dosage

Luckily during the “shortage” you can currently get GLP-1’s in vials rather than injection pens.

The brand name GLP’s you can’t control the dose. But when you get it in a vial from a compounding pharmacy you can inject however much or little you want.

Not looking forward to ever using the brand name version specifically for this reason

The injection pen I have see has two marked dosages, but there is nothing stopping you from injecting more or less.

Basically it is a ratcheting mechanism where after ~10 clicks you get .25 mg dosage and 20 clicks gets you .50. Basically, no doctor is going to endorse it, but you can dial a dose to whatever amount you want.

Aren’t any states like California trying to ban compounding pharmacies? It’s an unfortunate attack on individual freedom, but I am not sure if we will still have them 20 years from now.

> Aren’t any states like California trying to ban compounding pharmacies?

No. California has not banned compounding pharmacies, nor is there a significant movement to do so in the legislature, among the people (who could do so by ballot measure), or a proposal by the governor to do so. California does require additional licensure for sterile compounding, but that is very much not a ban on sterile compounding or compounding more generally.

Relevant to GLP-1s, though, several state pharmacy boards (not California’s, as far as I know) have raised issues that compounded GLP-1 drugs that they have seen appear to be illegal, because they use a form other than the FDA-approved base form of semaglutide (which is only available from Novo Nordisk), and th3 form used is not itself approved for human use, and have taken steps to crack down on that. But that's also not banning compounding, but enforcing existing rules on compounding.

I think the issue is more the FDA has hit compounding by announcing semaglutide and tirzepatide are no longer in shortage - so compounding pharmacies aren't legally able to sell the cheaper compounded versions. Since most insurances don't cover GLP-1 for weight loss, this is a huge issue given they cost almost $2000/month in the US out of pocket.

I was approved for semaglutide but now compounding pharmacies like Hims are stating their cheaper (<$200/month) compounded versions are out of stock.

Last week the FDA said the shortages are over so compounding will probably decline as they get sued by the companies.

https://www.barrons.com/articles/eli-lilly-zepbound-higher-d...

what is happening is more complicated.

First, there's no legislation. What is happening is that the branded drug was in shortage so compounding pharmacies were legally allowed to step in under existing regulations.

The shortage status was first updated in the summer, and Novo went on a lawsuit spree. Suing everyone mentioning GLP on a website.

But, there have been more back and forths since, very recent.

TLDR what is restricted now is not the sale of the compound, but the manufacture of it. Therefore, you can keep selling inventory past the restriction, but of course that will either run out, expire, or be restricted as well. As of now, if everything stays the same, expect the last few compound pharmacies to run out of product at the end of Q3/25 .

However, I understand there's groundbreaking legislation being worked on that will dramatically change the status quo for the better, meaning more choice for end consumers and less profits for Novo.

I get vials direct from Lilly and can choose what dose I take. Ask your PCP to check out LillyDirect.

Hum, I don't know, here in the UK, no one is forcing you to do anything. I am free to chose if I want to step up, down or stay on the current dosage every month. And I took the cautious approach to only step up when I stopped feeling the effects at the current dosage, so 8 months in, I am only starting on 10mg (range is 2.5 to 15mg in 2.5 increments).

Is that really true? I remember reading that people with side effects often were given lower doses.

If you want lower dosage, then there's a simple trick: just use less frequent injections. For example, try one in 10 days instead of 1 every week. It will result in lower steady-state GLP-1 levels.

It depends. The 5mg, 10mg, and 15mg were the doses tested and recommended as maintence doses. The 2.5mg is meant as a starter to reduce side effects but since most people don't see results with it the recommendation is that you only take it for 4 weeks. The 7.5mg and 12.5mg doses are meant as transitional doses but you can stay on them longer than 4 weeks.

Some doctors will go by the Lilly recommendations but I think more are allowing people to stay on the lowest dose providing benefits. That leaves your health insurance as the only other obstacle.

There is a chart at https://zepbound.lilly.com/hcp/dosage

I was one of the rare people that saw results with 2.5mg but by the end of that first month I had plateaued. After 3 months at 5.0mg I've plateaued again and will probably move up to 7.5mg in the near future and stay on it as long as I can.

Some people like to go back to 2.5mg as their maintence dose after reaching their weight loss goals.

The inbetween doses are just used for titration. They were not studied as long term doses like the maintenance doses. It’s stupid, and you can get exceptions if you are persistent. I preferred 7.5 mg over 10 mg for example.

Thanks for experimenting with your body. I'll be sure to check back in about ten years to see how all this shakes out.

Keto + intermittent fasting are my magic pill right now and have been for some years.

Ozempic has been in use for diabetic patients for at least a decade if you want to look at the research of its long term results in that population - which is fairly large to constitute a good sample sizing.

So that means we'll have a good twenty years of data to finally look at, which is what I was saying. I do not trust any medicine unless it has far more data than what we have in this regard at this point. I work in a related field and I can simply say most things we trust should not be trusted and should require far more testing.

Then wait another 50 years, easy.

I'm pretty sure keto has not been extensively studied for anything but the management of epilepsy in children that do not respond to medication. So tbh this is an odd comparison.

Keto and such diets have been used for millennia. Our bodies are MADE to use keto... Lol.

I am much more daring in my will to experiment but I do agree.

Keto, fasting and also breaking the "foodie" culture that eating and going out to eat becomes a hobby.

I didn't order/dine in at all from a restaurant in 2024. It is much easier to not over eat the boring keto meals I make myself. My "cheating" is eating basmati or jasmine rice with a stir fry instead of cauliflower rice.

There is actually not enough known side effects for me to take GLP-1s. They are either complete miracle drugs or side effects we don't currently understand haven't come out in the wash yet.

We have a pretty good track record when a new powerful medication like this is introduces of doing things quite wrong. There are probably risk mitigation strategies we will learn in the coming decades that we simply can't know right now. Otherwise, these are basically free lunch miracle drugs. That seems an easy short.

The above describes me but it is the consequence of my behaviors/habits. Being a workaholic, I learned long ago to ignore the leash that pulls me to the refrigerator. It seems by brain no longer sends me a "you need to eat" signal similar to the way free divers can become oblivious to the "you need to breath" signal.

I wonder if with time, you can learn from this drug, form the helpful habits/behaviors and then stop taking it.

Probably not. If it suppresses your hunger response, you will likely lose the ability to deal with hunger when you go off it.

I understand that on population level we can't just tell everyone "get on a diet", but when talking to you in particular, why couldn't you... just get on a diet?

Personally, I love food. I can't live without stuffing candy in my mouth. But I also have a tendency to get fat, so I weight myself every day, and based on that I either have a diet day or a cheat day. Moreover, I do a lot of physical exercise every day. The idea of having to depend on a drug to live is scary to me.

Having said the above, I'm sure that one day we'll create a drug that makes life of majority of population better, and we'll be able to administer it to everyone without major consequences.

> That late night trip to McDonalds will have you feeling like shit the next day

I've never had this reaction to fast food before. I only eat mcdonalds every few months and yea it's not the highest quality food, but I don't think there's anything in it to make you sick any more than other burger places have. I imagine you'd have to have restricted fast-food nutrition for quite some time before you feel a difference.

I'd like to see a study comparing people who ate mcdonalds who thought of it like slop vs those who saw it as a treat. I'm curious how much of this is psychosomatic, or how much of the craving for mcdonalds is rooted in feeling like crap in the first place.

(Granted, I've never had an issue with maintaining my appetite before, in fact I have issues keeping weight on, so I might have a fundamentally different relationship with food.)

The way I read it, i think the original commenter would usually agree with you, but the effect of the drug turns the post-fast food / treat satiation from joy to pain.

I believe you're correct. Apologies for the confusion.

>> That late night trip to Mcs will have you feeling like crap the next day

> I've never had this reaction to fast food before.

I do. Because of it, I eat fastfood when I'm willing to pay that price, ~5x/decade.

> I'd like to see a study comparing people who ate mcs who thought of it like slop vs those who saw it as a treat. I'm curious how much of this is psychosomatic.

The notion that our psychology could be holding us back from fastfood completeness is one that never occurred to me. I like how novel it is.

I believe you, but what do you think it is in the food that causes such severe reactions for you but doesn't affect me at all? Humans lived through periods of extreme starvation and other forms of malnutrition—our genetics are extremely clear on this, as is our tendancy to cannibalize our muscles when they're underused. It seems absurd to me a slightly different selection of nutrients could cause acute distress. (Hence my recourse to psychology—which would map well with the shift towards the moralization of nutrition these past few decades.)

>I believe you, but what do you think it is in the food that causes such severe reactions for you but doesn't affect me at all?

Food sensitivities are primarily a lot of medical questions, for which we have few answers. For example many fresh breads will give me stomach cramps and Rosacea. I can eat those same ingredients+amounts in other foods and be fine.

Many fastfoods ramp my brainfog up to 11. I don't know why. I'm in a poor position to consider the issue while the brainfog is in play. I could consider it later but the best I can hope for is unsubstantiated guesses.

I think the appetite reduction is too effective for you because you didn't previously have an overeating problem.

For those who do, it makes them have a normal appetite.

Additionally, it seems to make junk food taste less appealing and real food more appealing.

I was in the overeating column (4000+ calories a day, no sugar drinks) and going into month 3 I am fighting to hit 1500 every day except the day before shot day and shot day. YMMV of course, but it is very effective for me so far.

> Eating is no longer enjoyable and feels like a chore

I used to view eating as a chore and it was great. Then (no joke) I got into tech and everywhere I work they have fancy food or frequent team lunches or something of that nature.

I wish I could go back.

The effects seemed to wane slightly for me, but it vastly changed my relationship with food. I was raised in a family with plenty of food, but food was used as a weapon of manipulation and thus I was taught to eat as much as I can else it might be taken away. With Zepbound I now eat appropriate portions. Can’t really stand more than a single beer. I don’t mind being at a restaurant and not really eating. I’ll have a bite of this or that and be happy.

My shits, however, have been glorious since starting the drug. Truly pleasant steamers that rocket right out.

Be careful with all this. At one point I had gone 72 hours without eating or drinking anything and one beer by the pool had me on the floor. I keep hydrated these days but sometimes it’s an effort.

Atkins-ish diet caused the same thing for me with a car accident back in the 90's. Sudden uptake of carbs with the alcohol resulted in lost memory of over 13 hours, a '68 De Ville convertible that got totaled and 2 months spent with a wired jaw.

Thanks for the report! Aside from the loss of interest in food, what other side effects have you noticed or not noticed? (other N=1 reports welcome!)

Interesting, this sounds like my normal state. I cope by only eating tasty calorie-dense meals and snacks, never skipping meals or snacks, and weight lifting to increase my appetite. Otherwise I become significantly underweight.

This is me without any drugs. I’m very interested in food, but I only want a few bites to taste.

One thing this comment ignores is the very non-zero chance, which increases with dose and time on the drug, of developing gastropwresis. Gastropwresis will ruin your life to the point where you may never be hale to eat normal solid food ever again.

> being overweight will be a choice (choosing not to take the drug)

This may be an ignorant take and if it is I apologize, but isn't it a choice anyway? A calorie deficit and minimal exercise will have you cutting body fat. Or am I missing something here?

It's possible your personal experience with food is different than other people's, and it is easier for you to make that choice than others.

That is fair. Most people in my circle are some form of endurance athlete, climbers, etc so I live in a bubble but some of the comments I see feel alarming- like an over correction in the opposite direction.

People aren’t computers. Eating fixation and compulsion empirically override the more rational mind in millions of people. One of the effects of these drugs is making eating a more “impersonal” or “detached” kind of decision, so it feels like a real choice rather than something that you think you have a say in but really the more base instincts will override.

There is a segment of people where GLP-1 medications just don't work, 68% stop within a year, and dosing keeps on escalating up and up. It will help a lot of people, but it is not going to be the panacea early results show.

Since you are not terribly overweight you could reach a healthy weight with relatively minor lifestyle and diet adjustments. Isn’t this preferable to the side effects (some probably unknown) involved in these drugs? Genuine question.

Did you experience trouble drinking non alcoholic beverages or just plain water?

The feeling of no hunger at all will dissipate in a few months, even as you increase dose.

You will probably land on "not often hungry". The feeling of being full very quickly when you do eat will stay

That's interesting. I started ozempic about 3 months ago and the effects are really not dramatic at all. Is Terzepatide supposed to be more powerful?

Tirzepatide is supposed to be more powerful, but GP also just appears to be relatively sensitive to the drug.

How exactly does one get a prescription for that without any apparent need for it?

What are the side effects ? I heard these drugs just freezes the intestine.

Depends. I tried Ozempic and felt fine but every time I bumped up the dose I’d feel a vague feeling of dread, until I got to the max dosage then I didn’t lose any weight but also felt like I was going to die at any moment. It was bad. I discontinued usage then immediately went back to 300 pounds from 260.

Zepbound/Mounjaro on the other hand has been fantastic. I just noticed I was hurting my muscles a lot and realized it was because I was losing muscle mass. I started taking protein shakes and that seems to have fixed it. Wish I’d realize it sooner as I’ve hurt my hip joint and can’t ride my bike which was primarily how I was exercising, so I need to go to physical therapy. I’m on 10mg and frozen at 260, have an appointment to go to the next dosage on Monday. Hopeful I’ll keep losing weight and get down to around 200.

Absolutely understand. Never had joint issues, but after being on Tz for a couple of months, I had knee and hip pain. I'm convinced it was muscle loss, because after I boosted my protein intake and exercise, they started to go away. All but gone now (thankfully).

> Even at the lowest 2.5mg starter dose which you're only allowed to stay on for 1 month

... what? Get a better medical provider, you can stay on 2.5mg as long as it's effective. Your hunger will come back. Going up every month is poor practice if you have hunger-suppressing effects, whatever the manufacturer says: speak to an endocrinologist who's experienced with prescribing it instead. The first couple of weeks I had no appetite, but I stayed on 2.5mg for three months and had a healthy appetite by the end, and continued to take it slow. Lost about 1kg a week, and enjoyed my food just fine.

Respectfully, you're in week 3, I think it's worth giving it a few months before you start sharing your experiences of it on the internet.

The much more common experience of this drug -- when you've been on it a little while and you've found a good dosage -- is you enjoy food, you have an appetite, you're just not ALWAYS thinking about food. There is enough anecdata in the many subreddits to constitute actual data about what a typical experience taking any of these things feels like.

How long before it started taking effect when you started?

How did you get it? I've wanted something similar.

Cocaine makes you feel really good and heroin is fun.

> After a few weeks on the drug, I'm 100% convinced that once this drug is widely available and cheap... being overweight will be a choice

It already is.

Yes. In the same way addiction is a choice.

Stopping opioids or alcohol cold turkey can kill you; stopping food will not, for a very long time depending on how much fuel you carry around.

I started in November and am down ~25 lb.

> Even at the lowest 2.5mg starter dose which you're only allowed to stay on for 1 month

Uh, you're allowed to stay there as long as you want. I was on 2.5 for two months and asked my Dr to up the dose, as progression kind of stalled in the second month. I've been hanging out around 3.5-4.5mg/week since then losing ~5 lb/month steadily.

Sounds like you're pretty sensitive to it, which is nice. You can lower the dose even further if you think it's too strong at 2.5mg/week.

It is definitely a game changer.

Any negative side effects?

Where did you purchase it?

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You can get wegovy generic for $299/mo and Zepbound generic for $399/mo currently through telemedicine via compounding pharmacies, without insurance.

Maybe they are in Canada.

Name brand Ozempic is $230 CAD or $160 from Costco up here

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What a take.

I have no idea what Americans overpaying for healthcare has to do with a Danish drug company participating in the Canadian Healthcare market.

I’d rather thank the Canadian government for having a drug pricing review process.

If these companies don’t want to sell their drugs here, no one is making them. They are still here, so I think it’s safe to assume that they are still making money.

I don’t think it should be controversial to say that if the US imposed a Canadian-style price control regime on more than the handful of drugs currently regulated by Medicare, the future number of drugs developed and commercialized would drop significantly.

It’s just basic addressable market vs. development cost math.

Would the number of drugs developed drop, or would a few luxury yacht companies go bankrupt?

The number of drugs developed would drop. In particular, the really expensive to develop drugs that target rare conditions, exploit novel pathways, or require difficult synthesis.

The kinds of drugs that routinely experience years of delayed availability in markets like Canada and the UK until the learning curve has kicked in via the US and other less constrained markets.

The drug companies in Canada are part of the drug pricing process. Their development costs are considered. In exchange, they get additional monopoly priveleges on patented medicine.

Canada doesn’t even have particularly low drug pricing compared to the rest of the world, the opposite in fact. Canada just had low drug prices compared to the most expensive market on the planet.

It’s possible that lower drug prices in one country would disincentivize a global industry that touches almost every human on earth. Or it could not.

It's unambiguously the case that the US subsidizes drug development for the rest of the world, including non-US pharma companies like Novo.

Just because they extract massive profits from the US market does not mean that they would stop operating if they only extracted healthy profits.

They would continue operating but fund less speculative drug development.

Maybe.

Personally, I think that they would cut other cost centers before they cut the only department that ensures their long term success

The industry could save tens or of billions per year by not advertising (this is a US thing, drug ads are nonexistent in many places), and eliminating pricing games, cost rebate programs, coupons, drug reps, etc. These are all significant costs and friction that don’t exist in most other countries.

My personal feeling is that claiming that the worlds least cost efficient healthcare system with many layers of added complexity is the driver behind pharmaceutical budgets is marginal.

And of course you have to consider that a significant portion of drug research costs are paid by government and other institutional grants

I'm sure Novo Nordisk would survive even with slightly lower margins.

Also what proportion of that $1,000 goes to the manufacturer? From what I understand various middlemen and such get a significant proportion of that without providing any value?

e.g. https://www.ftc.gov/news-events/news/press-releases/2024/09/...

"Eschew flamebait. Avoid generic tangents."

https://news.ycombinator.com/newsguidelines.html

So compounders can no longer legally sell tirzepatide and will soon (April-May) be unable to legally sell semaglutide.

If you don't cook, it is very easy to spend $1000+ on food in a month, especially if you live in a high cost of living area.

I'm single, live alone, work a lot, and earn a lot. Food delivery apps are hella expensive... but I still pay it quite frequently. Yes, I am ashamed, thanks for asking.

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