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.

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?

Everyone's on something and/or coping in unhealthy ways.

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.

Same as with drugs for hypertension, depression, hyperglycemia and many, many others. Not every drug is supposed to somehow permanently cure you.

"But you have to do it forever" shouldn't be a convincing dismissal after 10 seconds of thought.

If I stop going to the gym for a couple of months, I'm probably not going to gain any weight because I still eat healthy and stay active.

And for some people they will have to take this for life, which isn't so different from many other medications.

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).

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.

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?

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.

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.

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.

Could you elaborate on that? I'm currently still a smoker (working on it...) and on Concerta. Your note alarms me :)

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.

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.

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.

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.

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.

All of these diseases have significant input from bad diet and metabolic disorder. Alzheimer's is considered a variation of t2d in some circles.

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.

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.

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.

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.

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.

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.

So I guess if it takes me 10 more years to gain it back I can look into taking it again.

I went off for three months and kept losing weight throughout.

And the data from these drugs shows they gain it back at regular rate at most.

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.

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)

0: https://clinicaltrials.gov/ct2/show/results/NCT01720446?term...

It sounds like you're realizing what it's like to depend on a critical medication. The anxieties and risks you're describing are what people with diabetes, cancer, mental illness, HIV, 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!

https://en.wikipedia.org/wiki/Martin_Shkreli

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...

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.

[1] https://www.pgpf.org/blog/2023/01/why-are-americans-paying-m....

[2] https://vinecon.ucdavis.edu/wp-content/uploads/2019/04/cwe12...

All those obesity related heart complications will turn into an extra decade of cancer treatments.

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.

One month supply us about £135 which is about $170 at todays rate.

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.

http://www.cnn.com/2010/HEALTH/11/08/twinkie.diet.professor/...

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.

$12k is going to be less than the typical admission to a hospital (for injury, illness, heart disease, diabetes related incident.)

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".

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 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.

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.

My understanding is naive but I always thought it was no longer possible to fail to comply after this intervention?

[1] https://www.researchgate.net/publication/332884264_Gambling_...

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

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.

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?

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.

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.

Which do you think will be more successful?

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.

https://www.medpagetoday.com/special-reports/exclusives/9962...

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.

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.