121 Comments

There are some reports that buprenorphone causes weight loss (along with the other opiates). Of course, that wouldn't be a legal way to prescribe it and I can't imagine it's worth the dependence but I suspect it works (both from personal experience and some remarks online). Still, hard to tell since almost everyone using it is either shifting from opiates w/o a ceiling or abusing it so the effect could fade but I suspect there is some long term effect.

I just mention this for completeness as using it for weight loss seems kinda crazy.

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Did you mean to write this or its opposite (i.e. “weight *loss*”)?

>I prescribe a lot of people stimulants for ADHD, and my experience is that they rarely get any useful amount of weight gain.

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Regarding costs to the medical system it occurs to me that an effective weight loss medication might increase costs even more via the indirect effect of enabling people to live longer.

Maybe it won't be of the same order of magnitude but I remember going through the numbers during the tobacco lawsuits and the claim that smoking increased the burden on state medical systems was complete bunk once you adjusted for the cost savings as a result of early death. Of course, those states likely lost tax revenue as a result but that too may have been offset by pension/etc savings.

Don't get me wrong, I don't have any sympathy for the tobacco companies in this case but morally speaking the states deserved almost none of that money but they got it rather than the smokers.

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To put my 2¢ in, I'm a big believer—from personal experience, seeing others' results, Internet testimonials (least reliable, obviously), and reasoning, in the #Whole30, which is a Paleo-inspired elimination diet. I've never been able to sustain weight loss for months and months before. I think it goes to the heart of our obesity epidemic (and have some evolutionary theories as to why it works).

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I'm not sure how Adam is getting his $120 for a two month supply figure. Peptide Sciences is offering 3mg/$120, and Biotech Peptides is offering 3mg/$114. That's more like $120 for a *one week* supply.

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Sorting comments by topic is awesome, but also a lot of work. I wonder if there's a good way to delegate it or crowd source it.

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Nov 30, 2022·edited Nov 30, 2022

I feel super lucky after reading these comments after how much people have been paying. I have just a standard issue HDHP through work (Anthem/Blue Cross Blue Shield in NY). Typically the full $2,000 deductible each year is paid by Gilead's savings program when I get my first Descovy for PreP prescription filled in January, so I just end up with regular co-pays after that. The co-pay for Wegovy has been $60, and that's reduced to $25 with a savings card (and I pay the $25 with a FSA card, so the after-tax cost to me is only like ~$150/year).

I think one reason a lot of eligible people might not take this drug is that insurance requires preapproval, and most doctors either genuinely think you won't be approved or will tell you that you won't because they don't want to deal with the hassle. My doctor has a strong interest in obesity issues and was very enthusiastic about the drug when I asked about it, but initially he told me it wouldn't be covered by insurance. I came armed with the preapproval criteria published on my insurer's web site, which as I showed him were quite lax (>30 BMI to start, >25 BMI required for renewal, and must be on a diet/exercise program as well). Ultimately, he prescribed Ozempic to avoid the preapproval hassle, but he agreed to try for preapproval with Wegovy once there was a nationwide shortage of Ozempic and my pharmacy couldn't fill a renewal for a while. We had no difficulty getting approval once we actually tried. It seems the insurer requires preapproval to scare doctors from even trying -- and most of the time, that works!

In terms of efficacy, I've lost more than 20 pounds (>10% of my starting weight) over the past 8 months and definitely and still in a groove of losing, but I do think you need to diet and exercise and complement the effects of the drug. If you can be somewhat disciplined about dieting, the drug will help a lot by making you not hungry even though you're on a calorie-restricted diet where you'd otherwise be rummaging through the fridge. But you won't see nearly as much progress if you don't actively track what you're eating at least part of the time and try to hit a reasonable calorie goal. Early on, I wasn't doing any dieting and the drug kept my weight stable (after I period when I had been gaining) but I didn't really lose anything until I decided to get more serious about tracking calories, working out 5-6 days a week, etc. It's made that effort much more impactful, I think.

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Thanks, Scott, for the table of contents. Makes it easier to navigate long posts

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Wait, bariatric surgery is that safe? I was just told yesterday by a surgeon that I ought to have my gallbladder removed after a quick referral process and an ultrasound from telling my PCP I had some mild pain in my gallbladder area. And he was like, all the complications are highly manageable, and are less than 1% each. This is a really significant update on my understanding.

Man, I really wish this stuff had been around ten years ago, two of my family members might still be alive and happier than I ever knew them to be if they'd been able to lose weight.

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"I prescribe a lot of people stimulants for ADHD, and my experience is that they rarely get any useful amount of weight gain."

Could this be in part that if the stimulants you prescribe are actually treating ADHD, they are causing your patients to sit still more and thus expend fewer calories?

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The singular of “data” *absolutely is* “anecdote”, and the inverted version of that quote originally said “is” rather than “is not”. n = 1000 really is just a bunch of n = 1s!

Here’s my n = 1 on this topic: Metformin caused embarrassingly terrible stomach issues (for years, before a doctor who didn’t just go “of course the fat guy has a bunch of problems!” finally put two and two together). Ozempic injected abdominally caused random occasional throwing up. Mounjaro injected in the thigh is going well, assuming my current extreme fatigue is me getting over the COVID I had last week and not the meds; I’m currently worried to see several mentions of tiredness here.

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Regarding the "savings cards should be illegal", something similar from my history:

I have Crohn's disease and was initially treated with Remicade, which is expensive: like four-to-five digit price tag expensive. This turns out to be a bad thing for getting people to actually use your drug, so the manufacturers solution is a "rebate program". As I understand it it works like:

1. You get billed for the drug

2. Insurance negotiates the price down, pays whatever, charges you the copay/deductible

3. You pay insurance with a rebate card (essentially a debit/credit card) the manufacturer gives you as part of the program. Essentially the manufacturer is "paying themselves".

I, of course, appreciate a mechanism by which I don't pay thousands of dollars for a medicine I basically need to keep a chronic illness under control... but based on my (limited) understanding, it's hard not to see this sort of thing as essentially a scam against insurance: it seems like the patient and manufacturer conspire so that the insurance is the only one who ends up paying anything for the medicine, and the manufacturer can charge basically whatever they like for it.

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> Sorry, I’m still not understanding this. Usualy weight loss dose of Wegovy is 2.4 mg per week = ~10 mg per month. The best I can find on CanShipMeds is 1 mg pens for $300. Doesn’t that suggest you’d need ten of those = $3000 per month? Or am I misunderstanding and that’s supposed to be the price for a month’s worth of 1 mg pens?

Sorry! I was referring to the Rybelsus. You can get 30 14mg tabs for $300. My understanding was that 14mg orally approximately equivalent to 2.4mg injected, but I could be wrong about that.

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>I prescribe a lot of people stimulants for ADHD, and my experience is that they rarely get any useful amount of weight gain.

I’m very surprised by this; I’m down 10% just from the minimum dose of provigil (side effect) after 3 months.

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Just a small note, but for the Canadian Ozempic, the "1 mg pens" are four doses of 1mg ("Ozempic® 4mg/3ml from Canada".)

It's interesting that the 4mg and 2mg pens cost the exact same amount. The 2mg pens are the "introductory" version that last six weeks instead of four--you take 0.25mg/week for four weeks, then 0.5mg/week for two weeks.

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So thankful that you’re covering this in depth. Fascinating.

Has anyone figured out what the best insurance would be for covering Wegovy? I’m looking to buy new insurance anyway (self-employed/business owner) and would love to find one that would cover this treatment.

Sounds like at least one person is recommending Anthem/blue cross, but I wonder which plan?

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The only other drug I know of that is used for weight loss successfully is Clen. https://www.webmd.com/pain-management/what-you-need-to-know-about-clenbuterol-for-bodybuilding it appears to be extremely effective, It's a 30% improvement over diet/exercise alone. Clen is also illegal to buy so you need to find some sketchy russian pharma company to get it to you.

What makes Clen not an attractive option? Near as I can tell it's actually less dangerous than some other drugs I actually already take, and it fights perhaps the worst disease in america.

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I know of a company with a drug in clinical trials that causes weight loss faster and potentially larger than semaglutide and using a completely different mechanism that on theoretical grounds should be strongly synergistic with GLP-1 agonists. That company already applied for a patent on obesity treatment using a combination of GLP-1 and their therapeutic class. As they say, this changes everything! :)

I think that, as strange as it may seem from an observation of the American public at large, obesity has moved into the "solved medical research problem" category and all that remains is deployment.

Anecdotally, roughly one third of the female NPs at my ER are on semaglutide or equivalent drugs, and that's just the ones that told me about it. None of them are diabetic and they were not obese either, more like chunky. They report quite dramatic weight loss and, yes, many women working in the ED do appear quite a lot thinner than last year.

I expect that these and upcoming weight loss drugs will be much more widely used than you expect: Only the conscientious and the health freaks pay attention to e.g. their blood pressure, since hypertension is the silent killer that doesn't hurt until it's too late, so rates of compliance with treatment are modest. In contrast, obesity massively hurts people's love lives, and this creates a whole new level of urgency to obtain and conscientiously use the drugs that solve this problem.

I expect that in the next ten years Americans will collectively lose hundreds of thousands of tons of fat. There will be a tectonic shift in the dating market, which will be inundated by millions of lithe females and toned chads, fresh out of the weight loss clinic.

A new, gloriously thin future awaits!

A practical note on cheaper access to the drugs: There is one little trick obvious to anybody with a syringe that could reduce your cost of e.g. Mounjaro ($994 per month without insurance at Amazon Pharmacy) by a factor of six. I will not explain the trick because it could be construed as providing medical advice but, you know, it's obvious if you think about it for a moment.

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I think the shortage is affecting Canadian supplies and prices. While I was waiting for insurance approval, which mercifully came through, I got my Ozempic from Mark's Marine. The other popular Canadian pharmacy for U.S. residents is Candian Insulin. In early 2022, you could get a 4mg pen for $300. Yes, it's true, that doesn't get you to the full Wegovy dosage. It just gets you 1mg per week, which works well for me and for many others. But now when I check those sources, they don't appear to have the 4mg pens available right now.

This is a pain, but Novo Nordisk knows which side its balance sheet is buttered on, and I have confidence that they'll manage to ramp up production. That should make the larger pens available in the next year or so.

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This weight loss discussion has been very distressing to me because I went from just shy of 250 lbs in February to 160 lbs today through diet and exercise, and apparently I'm a freak who will inevitably put the weight back on. I think it worked because:

1. I live alone and cook only for myself so I basically have total control of my own diet most of the time. And I got really into breaking down the calorie count on every meal, weighing all the ingredients, calculating how many calories they are, then dividing that by the weight of the finished product for a calorie/gram total.

2. I used a calorie counter app and kitchen scale and got obsessed with tracking every calorie against my daily allowed total. It became sort of like a game where I had to pack all the food I wanted into the allowance + exercise total. At first this meant being hungry a lot, but gradually my diet shifted to lower calorie foods as I got "rewarded" for them by feeling fuller after eating them. I generally always have a bowl of salad in the fridge, because it fills out meals at basically no calories.

3. I discovered the secret of exercise is the treadmill incline. I am just incapable of keeping up running speeds for long periods of time, but it turns out I can easily push through very high inclines at anything below 4 mph. So I go slow(er) but really crank up the incline on an interval setting, and without my body constantly jerking up and down I can read books on my phone. If I'm reading while exercising, it's not boring at all, but the higher incline still lets me burn a lot of calories.

I'm pretty hopeful that even if I slack off and start putting the weight back on it will take a few years, and maybe I can achieve some kind of yoyo effect where I diet for six months, let the weight creep back up by a few dozen pounds, rinse and repeat. Though wow, I do miss ice cream a lot.

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"I see some bariatric surgery patients and I agree they generally do very well. The only disadvantages are: first, that surgery is scary. Second, that it’s irreversible and does leave you having a lot less appetite and ability to handle food for the rest of your life."

Half-serious question here: what is the risk of having this surgery, then like three years later I'm getting tipsy some night, beer munchies ensue as they have a tendency to do, I eat like three pieces of pizza and my insides explode?

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> GLP-1-proximal treatments

> https://twitter.com/DanielJDrucker/status/1591171488002232320?s=20&t=HWuGywdinWSLxCtYDJva2A

I roll to disbelieve, the results are too good to be true. A single dose leading to a 3-5 kilo reduction in 20 days? That's crash diet levels of short-term results. No reversal, and potentially even a continued downward trend for a month+ after the end of treatment? I choose cynicism, and will be thrilled if even a third of the claim holds up.

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This is great info, and even better with the crowd-sourced tweaks and additions!

Speaking of obesity, this article was in my Medscape bulletin this morning. Subjects are US children, & they're comparing brain MRI's of obese kids (17% of sample!) with those of non-obese.

Obesity Linked to Brain Abnormalities in Kids

CHICAGO -- Children with overweight or obesity appeared to have abnormalities in the brain that could affect executive functioning . . . Greater weight and body mass index (BMI) in typically developing 9- to 10-year-olds were associated with poor brain health . . . At higher weight and body mass index, we found extensive alterations in brain health, including in the gray matter cortex and in white matter fiber tracts, as well as the functional coupling of brain units . . . Essentially our work provides an explanation for previous research that has shown that obesity measurements are associated with poor cognitive performance and academic achievement

https://www.medpagetoday.com/meetingcoverage/rsna/101964?xid=nl_mpt_morningbreak2022-11-30&eun=g1760882d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=MorningBreak_113022&utm_term=NL_Gen_Int_Daily_News_Update_active

Yikes! Of course study says nothing about direction of causality but . . .

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Personal anecdote: I've been on Mounjaro for a bit over a month using the $25 discount card because my insurance won't cover it. I started at 6'4" 295 and have since lost 15 lbs with no dieting effort beyond simply trying to eat a generally reasonable diet. Side effects are mild at worst - no nausea per se though it's much easier to feel overly full at a meal, which feels unpleasant. I've also stopped feeling cravings for sugar after meals, which seems like a good sign that it's helping with insulin resistance.

After the discount card runs out, I expect I'll switch to semaglutide, so I can report back after the switch.

Two of my friends are on semaglutide - one has lost about 12 pounds in the span of a bit over two months, the other is just starting. Both had a hard time finding a pharmacy that could get it for them.

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Regarding the why-can't-you-fat-lazy-slobs-just-go-to-the-gym wars: I'm not sure people exactly enjoyed debating this -- seemed more like they couldn't help getting pulled in. The thread had much more of a Twitter feel to it than exchanges here usually do. This particular topic leads quickly to that kind of indignation machine that powers Twitter use. Lots of overweight people are in considerable distress about their weight and failure to change it, and lots of normal-weight people have a least a mild case of craving to fat-shame the overweight. Plus the empathy quotient of this group is on the low side, in my opinion -- consequence of group skewing male and techy, I think.

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My reaction to the prediction that Americas obesity rate has a fair chance of halving by 2050 was incredulity. So I googled obesity in the US and found that the prevalence of obesity has gone from 30% to 42% in the last 20 years, during which time the rate of extreme obesity has doubled.

Given that I'm also not really into predictions about something that may or may not happen by 2050, my incredulity wants to ask "When is obesity in America going to stop increasing?"

If one of the people who think that obesity is going to halve over the next 28 years wants to make a prediction about the ending of this increasing trend, I may well be interested in a monetary wager.

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Here's a dumb question: what is a “single-food” diet?

The extremes are easy to define. Only potatoes? Sure, that’s a mono diet. A 6-course dinner—not a mono diet.

What if you blend together a 6-course dinner and drink it at once? Have there been studies that measure how many fewer calories are consumed in that situation?

Is it driven by mono-flavor? Mono texture? Do people who lose their sense of smell also lose weight?

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Surgery is scary.

Before the innovation of laparoscopic surgery, a gall bladder extraction entailed a one-week hospitalization with a significant risk of short and long-term complications. Now, it is routinely performed as a same-day procedure.

Bariatric surgery has evolved enormously over the past 30 years and many centers now also offer bariatric surgery on an outpatient basis. The patient is admitted to the hospital in the morning and discharged in the evening.

Bariatric surgery today is even safer than gall bladder surgery.

https://doi.org/10.1007/s11695-017-2664-z

This high-quality meta-analysis studied 174,772 bariatric surgery patients who were pared with carefully matched controls. They concluded that diabetic patients who have bariatric surgery live 9.3 years longer and non-diabetic patients live 5.1 years longer than the controls.

https://doi.org/10.1016/s0140-6736(21)00591-2

Surprisingly, the major health benefit from bariatric surgery is not the reduction in diabetic complications or cardiovascular disease. It is the reduction in cancer!

https://doi.org/10.1097/sla.0000000000002525

The mechanism by which bariatric surgery works is not from the creation of a small stomach or malabsorption. Bariatric surgery causes major hormonal changes that result in reduced appetite. One of those hormones is GLP1, the same hormone that semaglutide also mimics.

One of the fascinating things that I have observed is that patients who take semaglutide or have bariatric surgery almost invariably consume much healthier diets than they did before! Oatmeal and fruits and vegetables suddenly seem to taste much better, and Eggs Benedict seems to lose its appeal!

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I know this is a tangent, but I was struck by "although I’m sometimes a little cavalier about pills I would be more nervous about things I inject into my body". I have the same feeling, but I'm curious whether that's just your gut reaction or whether it's a more informed opinion than my own gut reaction.

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The Diabetes Prevention Program was a 4-year RCT designed to determine if a highly structured Medically Supervised Weight Loss Program could cause long-term weight loss and thereby prevent patients from developing diabetes.

DOI: 10.1056/NEJMoa012512

It has been cited almost 12,000 times, making it one of the most frequently cited medical papers ever to be published.

However, if you examine that paper carefully, you will see that it actually proved the exact opposite of what it was purported to prove. It actually proved that MSWLP's cause short-term weight loss that is invariably followed by long-term weight regain.

The American Diabetes Association, the American Diabetes Association and the US Preventive Services Task Force have all published guidelines in which they recommend that obese patients be referred to MSWLP's and they use the DPP as the principal study supporting those guidelines.

MSWLP’s are highly profitable privately run businesses and many of the people writing those guidelines have major financial ties to those programs.

I have posted a20 minute highly evidenced based video on YouTube in which I review the DPP in some detail.

https://www.youtube.com/watch?v=wapjMQIpPAY&t=998s

And this is a somewhat more technical 10-minute video in which I dispute their claim that the DPP caused a 58% reduction in diabetes.

https://www.youtube.com/watch?v=wjN-1rPShC4&t=7s

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Yes, walking uphill and biking uphill obviously require additional energy. However, biking uphill on a treadmill would involve positioning the upper wheel at a higher position (than the lower) but have no effect on the wheel through which you deliver energy. It would obviously not require additional energy. The bike never loses nor gains altitude as the wheel can spin at an absolutely constant speed.

That a variable speed (throughout one's gait, while walking) WOULD cause you to gain and lose some altitude (during each step) was the point of the remainder of my original post... The closer you can come to a constant speed, the less difference there is between incline and not for a treadmill.

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I'm rather surprised no one mentioned food subsidies and cheap food being part of the problem. The USA cheap food policies and the massive amounts of money making that happen just might be related. Obviously this is an unpopular perspective and once you give people cheap food, it is hard to get into political office saying you want to triple food costs. If you give people cheap food, offshore or mechanise most the physical jobs, and go into a service economy, then it is no surprise you end up with WALL-E level morbidly obese people.

There has also been a very successful class war going on in the US for decades to erode wages and increase profits, so poverty would be a huge issue where the minimum wage is already creating hunger problems. So this is certainly not ideal to implement on its own. But I wonder why no one is talking about something simple like evaluating the cost of food in household budget vs obesity rates between countries and regions.

So while not necessarily a good idea overall, but in terms of a narrow fixation on obesity...make food more expensive/reflect the real costs of production would make a lot of sense. I can't recall exact figured, but typical household budgets used to be something like 30% for food and it is now around 10% the US where farmers sell corn for less than it costs them to produce it due to subsidies which cause an entire market to operate at an internal loss. And farmers plant right up to the fence since there are no limits on several of these subsidies. It is odd how food policy and tens of billions of dollar spent to that affect is just 'out of scope' in obesity discussion. Is it power blindness or ignorance from decades of citizenry being powerless because corporations annexed the government?

Also with the corptocracy we have and the media amplified backlash against a simple tax in NY State on sugary drinks...it would be hard to pass legislation to alter current corruption money flows - but I think if we taxed processed foods based on their sugar content, then that'd make a big difference. If a soda cost $20 a can instead of less than $1, then people would drink less of it. We have no problem taxing cigarettes or other vices, sugar just needs to be reclassified as a vice and taxed into near oblivion. There is simply no valid reason an extremely obese society needs to sell small cans of bubbly acidic sugar water with 50g of sugar in them when tens or hundreds of billions of dollars in productivity, heath costs, etc. are being incurred.

The minimum food quality standards should be increased and simple things like caloric maximums in mass produced food or preposterous serving sizes need to be changed. Why wouldn't a big mac be half its current size? I recall research by those fast food places where they decided to go crazy on the calories in each order because most people are not willing to order 2 burgers and pay for 2 meals, but they will get fat and eat more if you make 1 burger twice as big.

This is just not part of the conversation taht just like social media companies profit from anger and division algos...fast food places for decades have weaponised and intentionally drive obesity up as their core profit model! It is simply a valid and legal business model to kill your customers! Why should a nation of laws and people tolerate these homicidal business models to sell cigarettes, high calories fast food, and horrible chemical industries of all kinds which have endangered the entire human race by lowering sperm counts, causing cancer, and making us sick in numerous ways?

Are extreme ownership and profit protection activities by our neo-aristocracy which is a death cult to be raised above all other possible consideration in the universe simply the correct and right way to live? The highest moral imperative is an Ayn Randian fixation on making already extremely wealthy people slightly richer or more powerful? Because it is hard to see it any other way when the government pays for a negative corn market used to make sugar to sell soda for under a dollar and everyone is obese and dying. Very profitable and you're very sick and dead!

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Thanks for the post!

Are you willing to describe why you find the first three topics under "Tangents That I Find Tedious" are tedious to you?

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I'll make one last comment on my tangent but after this thread I promise to drop the subject forever.

Some other people in this thread have brought up the analogy between exercising and quitting addictive substances (cigarettes, alcohol, etc). I'll bring up another analogy: exercise and veganism. I will confess that I am not vegan or vegetarian even though I know on some level that eating meat is really really wrong, and whenever I've been proselytized to by vegans it's always made me upset in a way that I never felt upset at for bullying or homophobia directed at me. For the latter two, it's easier for me not to get angry because it's not something that bothers me about myself and I can feel a sense of moral or intellectual superiority to the aggressors. I wonder if the anger I feel from the former is similar to any anger that people felt reading my posts; if so, I apologize for that.

Part of my suggestion of opening state-run gyms or subsidizing gym memberships comes from what I would imagine it would take for me to go vegan. Right now I think it is a matter of convenience for me; it's hard to get enough protein for my needs on a vegan diet, and it would require more structured eating and shopping habits. Certainly if every restaurant had the same level of vegan options as meat options and meat substitutes were in more grocery stores and were cheaper or a similar price to meat I would have a much easier time going vegan. Just like in the example of exercise, there are some people that would be unable to go vegan no matter how convenient it is, and some people that aren't vegan for reasons other than convenience, but I still think that making veganism more convenient would result in more people going vegan.

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Re: stimulants and weight loss, this describes my own experience... kinda. I was not obese, but I was overweight, with noticeable amounts of visceral fat. Then I was put on 16mg of Concerta (ER Ritalin) daily. I found that, by concentrating my hunger (i.e. cutting down on snacking) I was better able to plan ahead and therefore eat healthier overall. I was also able to use the energy and willpower from the meds to start working out more regularly. As such, my scale weight didn't drop much at all, but my body composition noticeably shifted to much lower body fat and much higher muscle mass. For obese people, I imagine this might not work out as well for obvious reasons, but I can definitely see where the idea comes from.

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I find the emphasis on weight so... limiting. Only a few place emphasis on metabolic indicators you might measure with bloodwork, and about zero people place emphasis on the body's ability to work: strength, flexibility, and endurance.

I don't care if I have a high BMI or a low BMI, I care if I can pick up more weight than I could last week. I have never been able to stay on a diet to save my life (literally), but I have been able to stay on a diet design to increase muscle mass - eating for the purpose 'lose weight' was always a failure, eating for the purpose 'bulk up and recover from exercise' has been one of the easiest things (it does help that diet is heavy on protein - H.E.A.V.Y. 1g protein per 1 lb body weight per day). My focus has been on body composition (muscle vs fat) not amount of fat.

I just believe based on my experience the answer to 'why not just diet and exercise' is few people have exercise goals but have a weight/BMI goal that translates into calorie restriction which translates into failure for a variety of reasons. Exercise might become a part of that, but it is secondary to the weight goal - I exercise because I want to weigh less or get rid of that double chin. Instead, I suspect if people started with a physical performance goal (I want to bench press my body weight, I want to deadlift 2x my body weight, I want to run a marathon) that would lead to diet and other physical forms of recovery and self care with far greater success and compliance.

I'd love to take 100 high BMI people and task then with lowering their BMI, and 100 high BMI people and task then with a physical performance goal (like deadlift or a marathon) and see which group over time has great success in achieving their goal. In my head group A is 'You wear an XL or XXL shirt; your goal is to go down a shirt size' and group B is 'You wear a XL or XXL shirt, your goal is to go up a shirt size and deadlift your body weight' and I'd bet money more of group B achieves their goal and group B is healthier across a broad range of metabolic measures and outcomes.

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It sounds like the ideal diet drug would be one that targets your set point weight directly. If you could change that like a dial, you could rely more on your own body's weigh management mechanisms to burn off the extra weight. Also, since set point appears to be something that generally stays static, if a drug could move it, perhaps you would only need to take it for a short period and the impact would last. Perhaps this approach could "cure" obesity.

I hope someone is studying the biological mechanisms that underlie the set point weight, and how to intervene in them.

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Interesting wrt to the tiredness comment, since I remember a lot of SMTM potato study participants reported similar effects (not any overall lethargy, but sleeping many more hours).

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Semaglutide Non Medical issues

Availability:

Saturday's Wall Street Journal: "Why You Can’t Find Wegovy, the Weight-Loss Drug: Novo Nordisk underestimated demand for drug that went viral on TikTok and YouTube: by Peter Loftus and Denise Roland

https://www.wsj.com/articles/why-you-cant-find-wegovy-the-weight-loss-drug-11670108199

Focuses, as one might expect from the Wall Street Journal, on the impact shortages are having on Novo Nordisk's business .

On a practical level, in the first Quarter of 2022, there were a few occasions on which I had to go around to several pharmacies to refill my prescription. By summer, that issue had gone away and I have had no problems getting refills on request. I do not know what is happening outside of my hometown or in foreign countries.

Price:

I think Scott wrote that the price per milligram of Ozempic and Wegovy, which are both injectable forms of semaglutide, is the same. My doctor and I are discussing switching me from Wegovy 2.4 mg to Ozempic 2 mg as a maintenance dose. The prices in my area of the two formulations (both manufactured by Novov Nordisk) are given in the following tables derived from GoodRx*.

Ozempic 2 mg × 4:

CVS Pharmacy retail: $1,053; with GoodRx coupon: $922.50.

Walgreens retail: $1,070; with GoodRx coupon: $928.35.

Meijer Pharmacy retail: $1,083; with Good Rx coupon: $886.18.

Wegovy 2.4 mg × 4:

CVS Pharmacy: retail $1,590; with GoodRx coupon: $1,391.34.

Walgreens retail: $1,619; with GoodRx coupon: $1,399.94.

Meijer Pharmacy: retail $1,637: with GoodRx coupon: $1,327.44.

Note that the most important non price difference between the two formulations other than amount of the drug per dose, is that Ozempic comes in a single four dose pen and Wegovy comes as four separate pens.

Also note that WSJ article says: "Novo lists Wegovy at $1,349 a month", but that is not the list price used by any of the pharmacies surveyed by GoodRx.

For those of you who are unfamiliar with the US or the Great Lakes area retail merchants, CVS and Walgreens are both nationwide pharmacy chains. Meijer is a regional competitor to Wal*Mart and Target.

The two formulations do have different prices per milligram. Note that the cheapest Wegovy per mg is more expensive than the most expensive Ozempic per mg.

Per mg (highest -- lowest)

Ozempic $135.38 -- $110.77

Wegovy $177.93 -- $144.29

Further research reveals that both formulations are priced without reference to dosage. The 0.5 mg pens are priced the same as the 2 or 2.4 mg pens.

*If you buy drugs in the US and have to pay cash or have large deductibles or co-pays, GoodRx.com is valuable. They provide price information for most prescription medicines used in the US. they also have free coupons that get discounts on cash payments. It is accessible via web browsers and by phone apps.

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I note comments about prior approvals. There is a service to help navigate the prior approval labyrinth called Cover My Meds (CoverMyMeds.com)

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

CoverMyMeds' software automates the prior authorization process used by some health insurance companies in the United States, helping to save time and eliminate paperwork. Traditionally, prior authorization required phone calls and faxes between multiple parties; CoverMyMeds circumvents this by automating the process. Involved parties are able to view the status of the authorization as it progresses.

https://www.covermymeds.com/main/

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America's hispanic population is expected to increase significantly by 2050. Hispanic americans are very fat and are probably less able/inclined to get bariatric surgery or expensive weight loss pills, so this should cause one to update downwards at least a bit on the probability of obesity halving.

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Scott, I read the following tweet and was interested to know in your research on semaglutide have you found any evidence of the following:

"I expect prescriptions for GLP1s and SGLT2 inhibitors to go vertical, but they're not safe

In the long term, higher basal insulin will foment insulin + leptin resistance as receptors are increasingly desensitized"

https://twitter.com/GCRClassic/status/1602726776484073474

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Regarding #3 (Other Weight Loss Drugs), there are small molecule GLP1R agonists in development (there are many, many patents), and I imagine they'll replace semaglutide/Wegovy if they make it through the clinic. Novo has been struggling for a decade to make adequate amounts of semaglutide, but the small molecules can be made by the ton. So, wait 5 years and see where we are.

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If you search, you can order Ozempic at a very low price in Canadian online pharmacies, and many give a discount on the first order, for example, 5% off on the Insulin.store website.

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