glp1guide

Good, balanced article -- Ozempic is coming for gyms maybe in the weight loss segment, but looking good after you've lost weight is 100% in their domain.

> But gyms are still about building muscle, too. One common side effect for some patients taking these medications is muscle loss. So gyms are now starting to market their brands to existing members who say they are on GLP-1s, and hoping they can add memberships in the future as people on these medications seek to keep and build muscle.

While concerns of muscle mass loss from Ozempic/other GLP1 Receptor Agonists have been somewhat overblown, it's always good to do resistance training during weight loss for shaping the body.

The hedonistic treadmill is still running -- people are going to desire chiseled bodies after slimmer ones.

> People taking GLP-1s are “going to want the right professional facilities and professional personal trainers and nutritionists to help them,” said Bahram Akradi, the CEO of Life Time, on an earnings call Wednesday. “We are confident that this [GLP-1] mega trend will be particularly positive for Life Time.”

Another thing on which they are slightly burying the lede -- people who are on GLP1 currently have excess income.

> JPMorgan last year said that current GLP-1 users purchased around 8% less food — including snacks, soft drinks and high-carb products — over the prior year, compared with consumers who were not on these drugs.

> Food giant Nestlé plans to invest more in nutritious products that it says provides “benefits” to people on GLP-1 treatments, such as its Opifast high-protein shakes.

The even bigger buried lede! Junk food companies are about to have to adapt QUICKLY.

Also note that drugs like Ozempic (GLP1 Receptor Agonists) work in at least the following ways:

- slow down stomach emptying (which was noted)

- improving glucose disposal

- reduce appetite by affecting brain chemistry

GLP1 RAs are really really interesting compounds (I'm a bit biased of course)

Thanks for sharing your story, this is really awesome.

The GLP1 class agonist of drugs (semaglutide, tirzepatide, liraglutide, exenatide, etc) are really amazing, they might be one of the biggest changes to come around this century.

> my dr prescribed saxenda, and I’ve personally experienced a profound disinterest in food, even on the lowest dose of 0.6mg. It’s just made it profoundly easy to make the right choice when it comes to food, and to not over eat.

I think this is one of the biggest positive effects. Rather than simply shedding the pounds for you, GLP1 RAs really empower the user to make better choices (and at least experience what life is like without "food noise")

> I guess the reason I’m sharing this is because as someone who used to be truely massive, I understand the struggle, however, these new GLP1 drugs mean it doesn’t have to be that hard. Unless there is legitimate medical reasons why a person can’t take it, I think people who struggle with weight should consider it. (That’s just my personal opinion, I know not everyone will agree.)

It is absolutely wild some of the takes I see, researching GLP1 (I write https://glp1.guide). While it doesn't work for everyone, the weight of the benefits versus the side effects is absurdly positively tilted.

The only thing I can hope for is that with all the formulations out there that price goes down and availability goes up as fast as safely possible.

This is interesting -- one thing that people on HN also pointed out was the possibility of GLP1 gene therapy. It was the first I heard of it but:

The original comment (thanks to toomuchtodo):

https://news.ycombinator.com/item?id=39354361

Some follow up links:

https://news.ycombinator.com/item?id=38495653

https://news.ycombinator.com/item?id=39284781

"Stop working" in this case meant "losing weight without doing anything" presumably -- I suspect that the other effects of Ozempic are still present like reduction in appetite and "food noise" happening in the brain for most.

I'm all for GLP1 RAs (clearly, I write a site about them) but at some point it's unreasonable to expect the drugs to literally do everything. Maybe throw in some exercise or lifestyle changes on top to get past the plateau!

> And another wild card…as more people start using Ozempic, fewer people will eat these health destructive meals.

So it's one of the things I think could go either way (do people do more of the thing when it becomes cheaper? or less because of appetite suppression), and it's looking more like people are about to have a whole let less junk food as price of GLP1 RAs goes down and availability goes up.

Fast food and other unhealthy food producers may about to be entering a somewhat hard time.

See also this article which is kind of an ad for Sweetgreen by Bloomberg (just tin foil hat talking there), but points a bit in the direction I mean:

https://news.ycombinator.com/item?id=39459842

A someone who writes a lot about GLP1s, this is a very trendy phrasing of the situation.

Following the analogy, I do think we'll see these companies gain the weight back though -- we're in a recession (in some countries, officially) and once times are good again companies are likely to load up again, even with AI -- AI is going to let us do more. Maybe it won't all be productive, but there will be more.

> I cannot believe how much this stuff costs presumably in the USA!

> ...

> Why is it so much more expensive in the US for these drugs? I’m struggling to understand how a place with a way more massive economy and no doubt higher demand, but also more supply, is paying these insane prices?!

Yeah, this is one of the places where pricing is broken a bit.

I guess that GDP number has to come from somewhere.

> I just bought a box of Saxenda (liraglutide) (5 pens + 100 needles) yesterday for $492 which is like the equivalent of $300USD and I didn’t use insurance or anything to pay. > > All up including the cost of getting my Dr to do the prescription it cost me $511. Which where I live this is considered expensive because most medications are free except for certain ones like saxenda. The hardest part of accessing GLP1’s where I live is that I’m in a tiny country and the manufacturers only supplies a small amount, so waitlists for the drugs are like 5 months long.

I do wonder how long until we see more international sales of these drugs... Found a super high quality article on this from KKF[0] -- it looks like we may be making some progress on allowing more international drug importing soon.

[0]: https://www.kff.org/medicare/issue-brief/10-faqs-on-prescrip...

> It would be good to compare this to diet and lifestyle change.

I agree here but this is notoriously hard to test/coordinate.

Any long term success of these drugs (or anything else) does have to come with diet and lifestyle change though, so maybe the point is moot? Measuring degrees of lifestyle change would be even harder still.

Not even thinking that lifestyle change can go the other way -- we're generally talking about improvements in eating habits or regular activity or whatever, but that stuff can also get worse! Hard to control for.

I guess the first step is to invent mind control, then once we get past those silly little rules around experimenting on humans we can finally figure out the truly optimal mix of medication and lifestyle change (this is a joke).

> I would prefer diet control to Ozempic due to the potential risk of cancer, but understand that others may choose to make different tradeoffs.

Yeah I personally think that for many the answer is still diet/lifestyle changes and not necessarily GLP1 RAs.

It's nice that there's a new option that is at least way more effective than the previous floundering people did though. The weight loss drug landscape is littered with terrible ineffective solutions.

Oh also note that the very same drugs are cheaper elsewhere -- retail prices are indeed still around $1000, but in other countries and on insurance it's cheaper.

Insurance companies are in the process right now of trying to restrict coverage to anything but type 2 diabetes patients right now.

The average American household absolutely can't afford this -- but then again the cost of medical care due to comorbidities that result from obesity are pretty expensive too.

Some people are resorting to compounded versions of these drugs (which is a terrible idea, IMO) to save money as well.

Yes there is, you can just stop, what is this stupid clickbait title.

There is research into whether weight regain happens, and most (over 50%) of people keep some weight off after getting off the semaglutide (and tirzepatide).

Wrote about it here[0], and the the study linked is:

https://www.epicresearch.org/articles/many-patients-maintain...

If you look at the STEP-1 and and SURMOUNT-4 trial extensions, the registered around a 6% drop in body weight after stopping.

Price needs to go down and availability needs to go up, but the narrative around people regaining all their weight back after stopping is silly.

Most importantly of all, people on these drugs might have a way to finally escape problems of food addiction because the effects are also psychological.

That said, there are certainly side effects, the drugs aren't magic -- they don't work for everyone and they are expensive (right now), etc. The fearmongering is annoying though.

Even from the article itself:

> A commonly cited 2022 study funded by Novo Nordisk , the manufacturer of Wegovy and Ozempic, found that patients regained two-thirds of their lost weight a year after they stopped taking semaglutide, the main component in the medications. Wegovy is approved for obesity treatment. Ozempic is approved for Type 2 diabetes, but many people take it off-label for weight loss.

So... People kept 1/3rd of the weight they lost off for a year?! This should be lauded.

[0]: https://glp1.guide/content/do-people-regain-all-the-weight-l...

BTW, this took a LONG time to make -- I know I should be doing it with an LLM or something, but it's too important a subject to not less the information pass over my relatively smooth brain wrinkles.

Great to see lots of active research and results getting published, even if there are a bunch of meta-analysis/reviews.

Ah there was a similar article earlier -- note that there is a supply shortage.

Excited to see if Chinese manufacturing brings a safe & effective alternative to some of the common formulations that can put pricing pressure and bring price down and increase availability.

IIRC the Sinovac vaccine was not super effective, but at this point there are so many formulations of the drugs, and plenty of Chinese researchers producing research (I see them every once in a while during my research paper roundups[0]) studying effects that it seems like china could catch up here.

That said, China getting into the GLP1 RA space is probably the last thing Novo Nordisk and Eli Lilly want.

[0]: https://glp1.guide/tag/research-roundups

Ozempic (and the wider class of GLP1 Receptor Agonists) is about to do an insane amount (good and bad) for so many sectors of the economy.

Do people consume more McDonalds/Chipotle/Coca cola/<your favorite junk food here> as a result of being able to more easily lose weight? Or do reduced appetites mean changed food habits?

With this survey (in the linked article) I think we're getting closer to our answer. Scott Galloway for one has been thinking/speaking about this lately in his weekly podcast -- early on he was suggesting downward pressure on the junk food companies, he might just be right.

So far data shows that most people keep the weight off after a stint on GLP1 RAs, but weight regain was also common, and which I imagine is a result of food habits not actually changing.

This is interesting, up until now there's been research coming out of china on the GLP1 Receptor Agonist class of drugs (*-glutides, ozempic, wegovy, mounjaro, etc) -- I wonder if we're about to see a bunch of chinese formulations hit the market.

If China has this problem at large scale, they might move a bit faster than others to rectify the accessibility/price issue

This is really solid advice -- changing the idea of losing weight to being less about "calories in calories out" and more about managing insulin is probably worth doing.

The "how" of releasing fat that you've laid out here is a really excellent explanation -- a lot of trends like intermittent fasting gets these results, but there's not enough discussion about the how/why laid out like you just have.

Would you mind sharing some of the resources you built this view from? You noted some sources below, but if you've got some more specific stuff you looked at, would love to read it.

GLP1 RAs do reduce "food noise" and cravings, but remember they don't necessarily work for everyone and do have some side effects that can be severe.

Most of the anecdotal data is right on though -- cravings are lessened, you stay full emptier (the result of delayed gastric emptying), and should even think about food less.

That podcast is epic, made a post about it on my site JUST to get more word on it out there. Acquired always does excellent write ups -- the competition between Novo and Lilly is also pretty interesting.

> The patent system is what promotes R&D. Once your patents expire anyone can manufacture your drug without ever having done any of the initial work. Drug companies have a pipeline of new drugs going through the decade of studies and trials it takes to bring them to the market and the ongoing survival of the company depends on some of these being a success.

This is our current system, but I'm not sure it's the only system. There could be a world where medicine moves forward without patents, but that might be a worse outcome for patients -- assuming we wanted to keep profits even across a patent & not patent system, patients or some other revenue stream would have to make up the shortfall.

> Would love to see some of the people here crying about obscene profits try their hand at investing in pharma companies. Its an easy way to lose a lot/all of your money.

Also, I think most reasonable people would not immediately take to investing in random pharma companies -- you'd do quite well to simply invest in the biggest companies, or an index. The charts for the index, novo and lilly are pretty decent.

So a bit late but this is definitely a thing, but as far as I know, with any kind of rapid weight loss, the loss of muscle "lean mass" can be an issue.

Did your doctor warn you by any chance about the cracked vertebrae and the interplay with losing weight/muscle? I'm assuming not but that is definitely not the kind of pre-existing condition that someone might notice (though I'd hope a doctor could notice/forsee that)

Starting to pair lifting weights with the treatment seems to be what everyone is suggesting is figuring out now, much like you did[0]. Along with that, probably some remodeling of eating habits is required (instead of just eating less).

[0]: https://glp1.guide/content/can-glp1-drugs-replace-diet-and-e...

Well some might be brave enough to do the but I’m certainly not!

Cant wait until availability grows up and price moves down though.

> Ha, I was going to start an info site just like yours, did the keyword research and registered some domain names, but other projects took precedence.

I'd love to hear about what you were going to do! If you want to chat I'd love to -- reach out to victor@<the domain> or admin@<the domain>.

> Like almost everyone else, I heard about them through the media, and then booked in to see an endocrinologist. Various subreddits have been great, with a particular shout out to the Mounjaro one

Yeah, there's a ton of great information on the subreddits -- I've found some to be more about encouragement, and then others to be more about fact finding (which I'm spending a lot of time doing now -- working on a research roundup for January 2024).

This is awesome -- I've heard it described as "food noise", and luckily I've never had to struggle with it, but hearing the anecdata is super amazing. They don't work for every single person, but there's no way GLP1s won't legitimately change the world. They already are.

How did you get into GLP1 RAs and where did you initially search for information about them? Was it a recommendation from your doctor?

Well it's tough competition, but at the end of the day eating too much (of anything) does bad things to people and makes them feel bad.

Ozempic (and other GLP1 RAs) helps people get to their goal weight -- they don't work for everyone but they do work to lower cravings for those other foods, for most people.

A lot of information flying around but if you want to see some of the studies that pointed to the loss of "lean body mass":

https://www.nejm.org/doi/full/10.1056/NEJMoa2206038

https://www.nejm.org/doi/full/10.1056/NEJMoa2032183

IMO one thing worth considering is the amount of muscle loss that occurs during regular rapid weight loss -- not enough studies have done comparison (I assume since it's very hard to induce the latter state).

It is interesting to think about the possibility that rather than decreasing the amount people go to the gym, GLP1 Receptor Agonists (Ozempic, Wegovy, Mounjaro, Zepbound, etc) might increase it.

I've written a little bit about this here[0], and while I don't always cite YouTube doctors, Doctor Mike Hansen has a pretty good evidence-heavy take[1].

For example one thing he gets into is that Tirzepatide (ex. Zepbound, Mounjaro -- the only one FDA approved for weight control) is more successful at fat loss relative to Semaglutide (ex. Ozempic, Wegovy, Rybelsus).

[0]: https://glp1.guide/content/can-glp1-drugs-replace-diet-and-e...

[1]: https://www.youtube.com/watch?v=ScBx37MBZ2s

Yup, and it does that in multiple ways -- both reducing your desire to eat too much as well as slowing down digestion.

> This makes me wonder whether a piece of installable software that 'suppresses appetite' for computer/phone use might someday become widespread.

Yeah -- I think if we can get a better grasp on how the reward systems of the brain work/how this could be a huge thing.

Actually if I think about it, the means might already be out there -- we're just not serious enough about the problem as a society yet. Regulation at the top level will probably come first at this point before a novel (likely expensive) treatment from a startup.

That aside, with how human nature is, I wonder if we'll see the pendulum swing back into society valuing (and thus assigning status) to people who are free of that addiction.

I think it'd be bad for internet companies that are heavily tilted towards addictive online activity -- the ones delivering value will probably be mostly fine, because they have at least some "tool" component.

For example Netflix -- as much as it can be an addiction/coping mechanism, it is legitimately a tool for enjoyment in healthy adults (essentially replacing/competing with going out to a movie theater by yourself or with others).

Yup. This is what's more likely to happen, a huge dip in profits for companies making addictive food.

Scott Galloway has been surmising this from the rooftops for a while now.

Well you could consider these drugs life-saving -- it's just over a different time frame.

So I also agree on this take, but it's diametrically opposed to another view, that the processed food industry will suffer greatly.

The drugs are appetite suppressants, I personally lean on the side that the companies making junk food will suffer, because people will just not want to eat as much if they're on the drugs.