I'm more worried there's some plausible way (like the ginger discussed) to negate the GLP-1 agonist's function itself or its net effects.
They're not going to talk about it in open industry journals, but Big Tobacco actually did do this with engineered high nicotine tobacco used to adjust addictivity levels.
The one thing I will literally eat an entire Costco sized pack of even while on my max GLP-1 dosage was Biscoff cookies. Not much else that I could "eat through" the drug when I was at my peak weight loss phase.
Per my link above, it's just evidence they're reacting to it, but I suspect there are more nefarious things going on they're not posting in public trade journals.
The "prize" I'm referring to isn't a literal X-Prize for addiction haha, but I mean market share, etc. is very worth investing in this.
Hah! This website throws up a modal and blocks browser-native Copy Text functionality with both Ctrl + C and right click > Copy. Haven't seen that in a long time.
I expect a second-order effect of cheap GLP-1s ending obesity will be to relieve the pressure on food manufacturers to make their products actually healthier
There are many other risks* than obesity from consuming UPFs, and we may find we've just removed the main stop-loss on worse outcomes
*Diabetes, all the biome/gut stuff which is getting better understood, colon cancer, etc etc
The thing about second order effects is that they are almost never larger than the first order effect.
Furthermore, GLP-1 users report having fewer cravings or just reduced appetite in general, whereas what you describe would require some sort of "calorie reduction pill" which would allow people to lose weight without altering their relationship to food. But that pill does not exist.
> The thing about second order effects is that they are almost never larger than the first order effect.
Sounds clever but this is just a labeling trick. When a second order effect is larger than the first order one, we just rename them to first order and intermediate effects.
For example, the first order effects of growing GLP-1 prevalence are actually consumption of prescription pads, new demand on pill bottles, and gas consumption of pharma sales reps.
The second order effect is weight loss in patients who take the drugs.
Cute and thus worthy of an upvote, but whenever I see scientists or economists refer to first or second order effects it pertains to things that are subsequent to each other in time, or at least intended vs. ancillary. I don't think anyone except for a Stafford "the purpose of a system is what it does" Beer acolyte would designate new demand of pill bottles as the first order effect of a new medication.
It's just something that statisticians have observed across many fields: you theorize about how potentially huge a particular interaction effect or knock-on effect could be relative to the main effect, you read about the Jevons Paradox and intuitively feel that it can explain so much of the world today... and then you get the data and it just almost never does. No reason why it couldn't, just empirically it rarely happens.
The demand for pill bottles literally does grow before anyone takes the medication, no?
And correct I agree they wouldn't designate the demand for pill bottles as the first order effect. That's because despite happening first, it's not the most important object of analysis. That's why it's a disproof of your earlier claim that second order effects aren't more significant than first order ones: because if they were, they'd be considered the first order effect.
> The demand for pill bottles literally does grow before anyone takes the medication, no?
Only really in the US. In most other countries they use blister packs instead. Global consumption of blister packs is so huge (not just for prescription medications, also OTC, vitamins, supplements, and complementary medicines), even a blockbuster medication likely only makes a modest difference to manufacturer demand in percentage terms.
> For example, the first order effects of growing GLP-1 prevalence are actually consumption of prescription pads, new demand on pill bottles, and gas consumption of pharma sales reps.
I take injectable tirzepatide prescribed by an electronic prescription… so impact on pill bottle demand and prescription pad demand in my case is literally zero.
And I doubt pharma sales reps have a lot of work to do selling GLP-1 agonists-who needs to convince doctors to prescribe a drug when there’s dozens of patients inquiring about it?
Yes the article is about pills, but most people are on injectables still (that may change over time). It likely has increased demand for needles and sharps containers. But in dollar terms, that’s a small percentage of the demand for the medication itself.
On the contrary, it may force them to make the products healthier. I've heard many GLP-1 users reporting an aversion to processed foods and cravings for healthy food.
I was thinking exactly this. People consume processed foods because they highjack our evolutionary responses. If GLP1 agonists make people immune to those high fat, big carb diets, perhaps we would see a decline of these strategies and instead seeing companies compete for the low appetite of people through smaller quantity yet high quality foods, rather than fast large quantity food.
This feels overly optimistic. You want to optimize for existing foods that are still high fat big carb and don't have the quality qualifier. I'm not familiar with the biological pathways that GLP1 operates on but I'm sure food companies will be working on adversarial products
Eating healthier for a while itself will reduce your palette for these foods, and make normal food taste better.
If you limit your sugar intake for a bit, American bread becomes quite the tasty treat.
It might not be direct action of the medication, but the medication making it easier to fix your habits can have huge dividends, similar to how giving an ADHD person stimulant meds make them less likely to die from misadventure or substance use because they self medicate less.
I think the current NOVA Classification for Ultra Processed Foods is flawed and often drops food containing preservatives and stabilizers into the same bucket as nutritionally poor items.
It also doesn't do a good job distinguishing value or health outcomes from consumption and simply lumps all UPFs into the same bucket. In otherwords fortified whole-grain breads and sodas are both UPFs but objectively they are not the same in terms of nutritional value or health outcomes.
The NOVA Classification's intent is to flag products where processing replaces whole foods, or adds cosmetic or functional additives to engineer taste/texture. It doesn't really factor in actual nutritional value or health outcomes from consumption.
We need to come up with a better system to identify to denote healthy or unhealthy foods, and also to identify foods that contain ingredients that have unknown impacts on our health outcome. Our current regulatory environment is to permit until proven harmful, so having something to flag x-factor ingredients would be beneficial.
> pressure on food manufacturers to make their products actually healthier
Probably not. Food manufacturing is not high margin. The things that would make "products actually healthier" are higher cost both in terms of inputs and in terms of shorter shelf life.
If people eat less and total sales volume decreases, there will not be additional money to change products lines. Expect corporate consolidation and a focus on children and glp-holdout populations, similar to cigarette manufacturers.
Similar to vapes, I could see the development of "ceremonial foods" that are chewed but not swallowed, like gum but with broader effects. Imagine something that approximates the experience of the crinkly bag, oily smell and physical crunch sensation of chips that then evaporates after the crunch. It would maybe even have a double bag for discretely spitting out the too small to crunch anymore shards of a saliva-phobic food grade meta-material.
They'll just make the food more expensive. It's something they've been doing for decades, sneakily.
I remember the YORKIE bar which had the letters of the name stamped on each piece (it was a segmented chocolate bar).
Eventually someone in my house noticed the stamped letters were gone, turned out they moved to a smaller bar with only 5 segments. It was hard to notice otherwise.
In practice, food manufacturers actually market "protein fortified" versions of products for GLP-1 users.
The idea is basically that doctors recommend you keep a high protein diet while on the drugs because a calorie deficit without protein will lead to muscle wasting.
”From 2013–2014 through August 2021–August 2023, the age-adjusted prevalence of obesity did not change significantly, while severe obesity prevalence increased from 7.7% to 9.7%” [1].
What fraction of America’s severely obese are being treated for it? (What fraction refuse treatment?)
I would've expected that uptake was only beginning in 2022 and still vastly increasing through 2023 (plus the compounding loophole that allowed telehealth companies like Ro to really expand the target audience). 2024 and 2025 data are likely to be better telltales of the impacts of GLP-1s.
I've been thinking of trying GLP-1's since I have not been able to put off the extra weight I've gained since covid. I'm in my 30's now and I feel like around this age I am starting to feel the effects of this extra weight on my body.
What is HN's experience with using GLP-1 inhibitors, for those who have used them? I've heard of side effects like bone density loss, but I've heard those side effects are caused by taking too large of a dose.
Bone density loss is a side-effect of losing weight. GLP-1s cause you to lose weight. You counteract that the same way you counteract it during all weight loss: Each day, eat 0.36 grams of protein for each pound (lbs) of healthy or lean body weight (i.e. you don't need additional protein for your excess body-fat, so use lean/or hypothetically healthy weight). Exercise inc. resistance training. For example if you would be 180 lbs at a healthy weight for your height, eat minimum 65 grams of protein.
Both of the two available GLP-1 have similar side effects, with Tirzepatide being lower at an equivalent effect dose. Their common side-effects are: Nausea, vomiting, diarrhea, and indigestion. With rare serious side-effects being: Pancreatitis, allergic reaction. thyroid cancer, and acute kidney injury.
Generally speaking the common side-effects are dose-dependent. If you suffer too much, you back off the medication until the side-effects are at a level you can manage. This is common.
I've been on a low dose for a year. I've lost 25kg (60 lbs) without much effort. Yes, it definitely dulls my appetite, and if I want to have a nice meal, I need to plan ahead for several weeks so that I have it _just_ before my next injection. There's also the fact that I didn't realise how important snacking was to my mental health. Since I don't have that, I've had to find other ways to boost my mood.
As a brief summary, it absolutely delivers what it says it does. I've lost weight as it claimed due to appetite suppression and feeling fuller longer. However, it's more complex than that, and the battle to ensure I get enough protein has been tough.
The bone density and muscle wasting are a product of a calorie deficit without protein or weight training. You'll see the same effects without GLP-1s if you just diet and don't actually lift.
As confirmed by DEXA scans, I maintained my (very high) bone density and actually put on about 3lb of muscle over a 2-month period on low-dose GLP-1 + a GHRH, while losing about 16lb of my most stubborn fat, including visceral fat that I hadn't been able to crack. I'm in my 40s, and my routine includes weight training, a high-protein diet, and Brazilian jiujitsu.
My approach is minimum effective dose as an amplifier to a good diet and active lifestyle, and it's been pretty damn effective. Primary effects are an effortless relationship with food - the "itch" I used to feel to eat constantly is pretty much gone, and the psychological pain of not eating things is more or less nonexistent. I did a 36 hour fast just to push it a bit, and it was trivially easy.
Side effects include an elevated heart rate (~5-8bpm, in my case taking me into the low 60s at rest) and sweating all the time, both of which are almost certainly due to the glucagon agonist's thermogenesis effect. No problems with constipation, though stools are harder (comparable to those on a keto diet, in my experience). No particular ill effects otherwise. n=1, YMMV.
To be clear, that is the advertised effects, not the side effects. The idea is that if you over eat you feel terrible, but also you won't want to overeat since you'll be full.
Intermittent fasting, lifting, calorie counting. The problem is that I am only able to stick to those maybe for a few weeks at a time before I get off track and end up back where I started. Except with weightlifting, I was able to stick with that for a few years, but unfortunately you can't outlift a bad diet. My relationship with food has never been a healthy one, and it's been that way ever since I wad a kid.
It's an interesting industry that needs billions to bring a new drug to market. At the same time it creates a lot of value to a patient. But the manufacturing of a single dose is usually tiny.
Now how do you price that? The profits here will reward pharma investors and enable more investments in RnD of new medicines. I feel that's mostly fair.
The typical other solution for this is government grants for research.
It could work but there are problems in (1) the amount of money required and (2) the funding research -> getting votes pipeline is borked (credit assignment in general is borked).
I'm assuming by “research chemical” you mean "counterfeit chemical" - Quite a signal for society, of individuals willing to inject themselves with these due to lack of funds or lack of effort.
That analogy would hold if a counterfeit dollar were perfectly identical to a real dollar, totally indistinguishable, and nobody could possibly tell the difference. Most of the "research chemical" drugs out there are chemically identical to the marked-up pharmaceutical products. Not similar, identical.
When you are buying chemicals from unknown entities you are adopting the enormous risks that come with it.
Drug synthesis can get very complicated. Purity of the drug is unknown.
Which contaminants are present and what are their effects on your body? Unknown.
What if any recourse do you have if they poison you? Minimal to none.
Even if you have a trusted third party doing efficacious testing of the compounds, the consistency of manufacture will be unknown unless they also do inspections. While I have no doubt that you can have private entity do a far better job than the FDA if the incentives are right there will be no business there. Perhaps a charity could work? I have no idea how though.
Without coming from the manufacturer or being validated by an independent, trusted third party, you do not know that the chemical composition is what is purported.
I would say that it seems the vast majority of buyers on social media are convinced the drugs are coming from Eli Lilly & are being bought through "research" loopholes.
What is absolutely shocking isn't that we have a weird drug that finally makes you stop consuming too many calories. What isn't shocking isn't that you eventually lose weight by eating much less. What is absolutely shocking is that people are using it correctly; existing with heavy obesity can finally return to being a somewhat obscene life choice and not a cruel fate of luck.
Obesity mostly causes expensive problems years later. People stay in their jobs for an average of something like 3-4 years. By the time anyone has an issue, it's the next guy's problem (or ideally, Medicare's).
They should. Unfortunately a lot of incentives are not aligned. Due to the profit cap as a percentage of premiums, generally higher medical spending increases health insurance profits rather than reducing them. It's the same thing with PG&E -- the only way for them to make more money is to increase costs. It's exactly the opposite of a normally functioning market, and you see the same result in both cases.
There are more powerful forces than the profit caps, namely that the big insurers now actually also own the doctors.
And capped or not, the pay-vider structure allows intra-company eliminations to bury arbitrary amounts of money as "not profit" even though it effectively is.
And even if that weren't true, the expected coverage term for a US patient is ~4 years due to it being tied to employment, so there is quite literally zero incentive to address any health issue that won't materialize as cost in the next few years (obesity being one such type of health problem).
> And capped or not, the pay-vider structure allows intra-company eliminations to bury arbitrary amounts of money as "not profit" even though it effectively is.
Source? There are 7 large publicly listed health insurers with public financials, all underperforming SP500 for more than a decade. There are myriad other non profits such as Kaiser/Cambia/Premera/Providence/various BCBS/etc, all with public financials as well.
Where is all this fraud going? And it’s happening across hundreds of executive offices across the country? And getting past 50 state insurance regulators that have to approve prices for insurance?
That would be remarkable levels of corruption and collusion.
It's not "fraudulent" per se, nor does it require corruption or collusion beyond what people already openly accept when they accept the existence of payviders (which they shouldn't! Or at least not for-profit payviders).
Payvider: An entity that is both a payer (insurer) and a provider (medical practice). Most payviders also have vertically integrated PBMs (pharmacy benefit managers), pharmacies, and labs, all of which participate in the same scheme.
A few of the examples you listed are NOT payviders, they're just payers, and therefore do not have these levers available to them.
Vertically integrated companies evade profit caps on their insurance division by shifting money to their unregulated provider, PBM, or labs divisions. It's pretty simple: the insurance arm overpays its own subsidiary doctors and clinics and records these internal transfers as mandatory "medical care" which is recorded as loss on the insurance side. The parent company then pockets the excess money as unrestricted profit on the provider/PBM/lab side, effectively bypassing the legal limit on how much insurance revenue they can keep and completely destroying the incentive to manage costs through their insurance division, at least when those costs originate from their own providers, which given that e.g. UHG is now the largest employer of doctors in the US, is increasingly often!
Is it fraudulent, corrupt, or collusive for a health insurer to employ doctors who deliver care? Not per se, but it gives insurers the ability to more or less arbitrarily convert premium dollars into profit while still getting people to defend them with claims like "they've been underperforming the SP500 for more than a decade."
Here are a few sources about different constituent behaviors, though you'd have to do a decent amount of reading to stitch together the full picture of how this works:
> Vertically integrated companies evade profit caps on their insurance division by shifting money to their unregulated provider, PBM, or labs divisions. It's pretty simple: the insurance arm overpays its own subsidiary doctors and clinics and records these internal transfers as mandatory "medical care" which is recorded as loss on the insurance side. The parent company then pockets the excess money as unrestricted profit on the provider/PBM/lab side, effectively bypassing the legal limit on how much insurance revenue they can keep and completely destroying the incentive to manage costs through their insurance division, at least when those costs originate from their own providers, which given that e.g. UHG is now the largest employer of doctors in the US, is increasingly often!
Yes, UNH does better than the other managed care organizations because their healthcare business has higher margins than their insurance business. But it’s certainly not arbitrary, and it’s apparently not enough to make their shares worth buying.
More importantly, UNH competed against other insurers. They don’t get to “arbitrarily” pay their doctors (as if any business wants to overpay their employees). If they pay too much, then they will have to charge higher premiums. Premiums which also have to be approved by state regulators. And it’s a fact that UNH’s premiums are comparable to everyone else’s premiums. Why else would people buy from them?
>Is it fraudulent, corrupt, or collusive for a health insurer to employ doctors who deliver care? Not per se, but it gives insurers the ability to more or less arbitrarily convert premium dollars into profit while still getting people to defend them with claims like "they've been underperforming the SP500 for more than a decade."
The silly claim is stating managed care organizations are booking outsize profits, yet they don’t show up in 10-Ks or even shateholders’ pockets.
Underperformance relative to SP500 is a factual claim. 2% to 3% profit margin (objectively a tiny profit margin is a factual claim for 6 different businesses. UNH is at 5% to 7%, which is decent, but pathetic compared to tech/pharmaceutical/finance/real estate/oil companies.
Hopefully you can see why this all sounds like unfounded conspiracy theories. Just the fact that it’s better to own SP500 than a health insurer stock should be enough to conclude there are no “unrestricted” arbitrary profits being taken. They are very much restricted, and their shareholders know.
> Yes, UNH does better than the other managed care organizations because their healthcare business has higher margins than their insurance business. But it’s certainly not arbitrary, and it’s apparently not enough to make their shares worth buying.
> The silly claim is stating managed care organizations are booking outsize profits,
Is this claim in the room with us now?
My claim is that the pay-vider structure enables these businesses to produce way, way, way more money than their regulatory "profit cap" leads people to believe. They can remove what would be profit from their insurance arm (where profit is capped anyway, so it keeps them under the cap) and dump it into their healthcare arm (proven by above-market self-reimbursement rates) to fund network expansion, which then further strengthens the insurance arm's market position (alleviating their need to "compete against other insurers" [ lol ])
Your claim is actually concordant with mine, which is that this profit doesn't show up as margin and doesn't show up as excellent stock performance. Correct! That's what it means to hide profit in order to stay below profit cap!
Anyway it's clear that I'm talking to a "stocks guy" who lacks the curiosity to actually understand how a business works beyond the 10-K (where all this stuff is discussed, by the way, you can find it euphemistically referred to as "network optimization").
Like I said, you'd have to do some reading well beyond the 10-Ks and the price chart lmao.
>Your claim is actually concordant with mine, which is that this profit doesn't show up as margin and doesn't show up as excellent stock performance. Correct! That's what it means to hide profit in order to stay below profit cap!
This definition of “hide profit” seems to be no different than “invest in the business”.
> which then further strengthens the insurance arm's market position (alleviating their need to "compete against other insurers" [ lol ])
Why is this “lol”? It is true that vertical integration results in efficiencies, and that can lead to lower premiums (not that it will absent sufficient competition). Kaiser has been doing it to much acclaim for almost 100 years.
I hadn't thought about the 4 year aspect. That is a great insight. I am against the current US healthcare system in general but I wonder if decoupling healthcare from employment (slightly) could help. Maybe employers should be required to pay for coverage that an employee selects? (clearly a lot of hand waiving of the exact mechanism here but..) This would incentivize healthcare plans to actually compete for someone to sign up with them and to give them an incentive to keep that person healthy since they would likely stick around longer with them.
The ACA makes it illegal for insurers to make the “punitive deductible” a function of one’s probability of needing healthcare, hence the financial incentive is for the insurer (who can bring down cost of claims, and hence be able to sell insurance at lower premiums).
Of course, the insured has the quality of life incentive of not having to deal with complications from consuming excess calories.
I love the two claims about health insurance companies: simultaneously denying coverage for needed healthcare, and "scaling" up their healthcare costs to increase profit.
There's no inconsistency in those statements, because there are also for-profit health insurance companies (that deny coverage) and not-for-profit ones (that balloon costs)
That premise must be invalid because if true, no one would buy insurance from for profit insurance companies. Their prices are all basically the same, approved by the same state government employees.
Plus the out of pocket maximums are a pittance compared to what complicated healthcare costs can be, so paying more for premiums to ensure you are not denied coverage would be a no brainer.
Alas, that is not the case, so the reality must be different from the premise.
Also, here's a non profit health insurance company denying coverage:
None of that invalidates what I said as a general rule for health insurance company behaviors that are also very well documented in media, so I'm not sure what you're trying to clarify for me here.
> That premise must be invalid because if true, no one would buy insurance from for profit insurance companies.
What premise? That companies balloon costs or aim to provide less care if they can get away with it? It's a complete non-sequitur if you think so.
>because there are also for-profit health insurance companies (that deny coverage) and not-for-profit ones (that balloon costs)
The claim that for profit health insurance companies deny coverage to save money and non profit health insurance companies balloon costs to maximize healthcare expenses is obviously wrong (as demonstrated in previous comment).
The claim that health insurance companies in general both deny coverage to reduce healthcare expenses and maximize healthcare expenses to increase profit is obviously wrong, because it's inherently contradictory.
>behaviors that are also very well documented in media
I don't see any documentation of this behavior. The documentation that does exist is the whole business limps along on a knife's edge, lagging SP500, while have no power to set their prices (the government has to approve their prices). They certainly do engage in outsourcing and underemployment, perhaps to intentionally delay and deny care, but probably leading to just as many incorrect approvals as incorrect denials (obviously you won't hear about the former in the media).
The for-profit ones have capped profits as a percent of costs(e.g. 80-20% rule).
Therefore, game theory predicts they support costs increases that are industry wide (raise all boats), and oppose them when only the company is impacted (lose market share or profit).
I wouldn't be surprised if this paves the way for differing insurance rates on health markers given how magical glp-1s seem to be, and how much of modern disease is based on lifestyle factors.
The amount of ingredient in the pill is huge relative to the shot, and you need to take it daily...which shows how hard it is to get drugs into the body.
Real question: given the dosage, how would you go about getting the pill and liquefying it? That would provide a huge, cheap supply of semaglutide.
It's not really different than losing weight by any other method in that respect.
There is always the risk of regaining weight unless you continue to do whatever caused you to lose weight (e.g. restricting calories) to some extent.
I guess a "cure" would be good but since we don't have one having to periodically go back on glp drugs if you gain weight is no different from periodically having to go on a diet if you gain weight.
On the other hand most people tend to naturally gain weight pretty slowly (e.g. a pound a year) so having to go on glp drugs for a period every few years wouldn't even be that bad, especially if they're available in pill form.
It is mixed. It can be a cure for some people. Last time I looked my impression it seemed like about half the people has only moderate rebound or less.
You have a lot of results that look like this, with an average bounce rebound of 2/3s of the loss.
However, detailed analysis usually shows a bimodal distribution, with people who maintain or even lose more, and those that go back or even gain relative to baseline.
Treating the symptoms can be helpful in the long term if symptoms are a contributing cause to the disease. I used to ride my bike 150+ miles a week, but after not being able to do so for a bit due to other reasons I gained some weight. At the level of riding I was doing, an extra 20-30 lb of weight makes riding far less pleasurable, particularly when it comes to going uphill or on dirt paths.
Just finding 10-12 hours in which to exercise every week is challenging on its own. It's much more difficult when the exercise itself becomes harder and less rewarding.
I fear the same thing but then people that know more about this say that these GLP-1 drugs have been used for many years (by diabetics) so they aren't untested or un-studied.
Literally from the Wikipedia article: “In 2002, Eli Lilly partnered with Amylin to develop exenatide and secure approval to market the drug. Exenatide's 2005 approval by the U.S. Food and Drug Administration showed that targeting the GLP-1 receptor was a viable strategy and inspired other pharmaceutical companies to focus on that receptor” [1].
There is a minor risk that a new drug causes cancer or something. However, obesity is a major risk for very large amount of health problems, including many cancers.
Obesity has a known, well established, multi-modal cancer risk, and then on top add metabolic syndrome (T2, heart disease, etc).
So, you're weighing a hypothetical risk against and establish risk, and concluding that the unknown risk is scarier than the known risk. Which is irrational.
Imagine if someone asks you if you want to take the "obesity pill," and you looked at the side effects objectively. But instead you weight obesity as "normal" and this as "new and scary."
To be completely honest I don't 100% trust the medical industry whenever there's so much money behind marketing something. There's a very real vested interest in trying to downplay the risk factors because let's just say tomorrow they found out this stuff makes all your teeth fall out.
A whole lot of folks would lose billions of dollars. My first instinct is to think I need to go and take another Europe. The food is better there and I lost a good amount of weight the first time.
Understood. You may be interested to learn that Liraglutide, a GLP-1 Agonist, has been commercially available and commonly used since 2010 (15-years+) without any unknown/unexpected additional side-effects appearing. It was developed in 1998.
The main reason GLP-1 Agonists are suddenly more popular is two things:
- Liraglutide had to be taken daily, instead of weekly.
- Nobody every paid for Liraglutide to be clinically approved for weight-loss. It was an anti-diabetic medication; but the mechanism of action is the same.
Compared with liraglutide, semaglutide was engineered mainly with a longer, differently attached fatty-acid side chain that increases albumin binding and slows clearance, so it lasts longer; both drugs activate the GLP-1 receptor.
Nah, you'll just be on it for the rest of your life. Drug companies prefer chronic illnesses since they cannot be cured, and recipients take the drug for life. All these hormones (GLP, testosterones, hrt) will need to be taken forever. Very few people come off GLP-1 and keep weight off.
I mean, obesity is a chronic illness, so is hypogonadism. If your balls don't work they don't work.
Chronic illnesses require chronic medication. The same is true even WITHOUT the medication. If you're obese and want to lose the weight, you need to manage your diet and exercise. Forever. Until the day you die. You can't ever stop that or you'll be obese again.
Some things just don't have one-time solutions, and that's okay.
Gilead has made bank on Solvadi, a drug that cures a previously-chronic disease [1].
> Very few people come off GLP-1 and keep weight off
Rebound can be close to 100% if you’re severely obese, but for most people it’s much less [2]. (Everyone I know who was taking it two years ago is off it, and they eat and exercise healthier than they did.)
That might be okay! I'm on the lowest dose of Zepbound (tirzepatide), 2.5mg, and I'm losing 5lbs a week, which is almost too much. It will be helpful to switch to something perhaps not as good in pill form (versus my weekly injections) once I reach my target weight. For those who need pill form and the effectiveness available, it's a slam dunk imho. Orforglipron [1] (small molecule by Lilly vs a peptide) will be potentially available shortly for those needing more effectiveness. We're making incremental improvements in this system rapidly.
Could also be great for maintenance dosing. I'm reaching the end of my ~weight loss journey~, and it's not a sure thing that the insurance company will continue paying for the injections once I'm no longer overweight.
I'm definitely willing to keep taking it. If insurance won't pay for it, I could pay for the pill out of pocket if I had to, which would be cost prohibitive for the injections.
5 lbs a week is crazy? Are you expecting asymptotic approach to healthy weight? I'm 185 and would prefer to be more like 170, but 3 weeks seems too fast.
I started at 170lbs and my target is 135lbs (early 40s male). My blood panel looks good per my PCP, and as long as I'm not losing weight so fast I have excess skin or I experience liver, kidney, or pancreas failures of any degree, that meets my success criteria. I am trying to shed as much unhealthy visceral fat as possible while using the pharma intervention to dissuade me from unhealthy consumption habits.
At $300/month cash pay through https://lilly.com, I find the ROI to be exceptional.
While I think BMI is fairly suboptimal and would defer to a DEXA scan, that weight puts me right in the middle of a healthy BMI for a human of my gender, height, and age. As mentioned, I lift weights, three days per week. This also increases my metabolism and daily caloric budget (beyond basal and resting metabolic rates).
My goal is to drop fat, gain muscle, and be strong with good cardio performance, and a GLP-1 turns off the part of my brain that made me carry excess unhealthy fat and eat the foods that made that fat. GLP-1s also promote thermogenesis, so it is turning on the switch to tell your body to burn fat that you would have to fast or get into ketosis via a ketogenic diet otherwise to get into (by first depleting your glycogen reserves). I do not get any fatigue such that I would when fasting or on a keto diet needed to encourage thermogenesis and burning up fat reserves, which is awesome imho.
My brain says "you are fine" instead "you must eat, feel hungry, and get hangry, even though you already have all of this fat." A bug has been patched.
Interesting. I also do weightlifting 3x/week and my weight is in the 190s (male, 60yrs old, 6' tall). I am definitely carrying some excess fat but think my ideal would be somwhere around 175-180. Have never done any BMI tests.
Indeed, I have to make a conscious effort to remember to eat, and consume 800 calories (two servings) of Creamy Chocolate Soylent (premade, liquid bottles) daily, along with fiber gummies to keep everything moving in my digestive track. I do strength training to preserve muscle mass. Desire to eat anything sweet or alcohol has gone to zero (RIP my craft beer desires and my sweet tooth).
How long did those effects take to come into effect? I have been on 2.5 for a week and haven't noticed a change in my appetite, though I have lost 2 pounds.
First week. You might need a higher dose, check with your prescriber. My partner needed to go to 5mg to see improved results, but dropped back down due to side effects (which I did not have).
My doctor does not approve or reject my actions, they simply make recommendations and provide guidance. I work with people who understand my risk appetite, which is aggressive. If you are not aggressive as a practitioner, I will work with someone who is. Unsophisticated humans need protection, which I understand and appreciate, but I need coaches and subject matter experts who will push me to my limits.
Indeed; there is a MASSIVE market demand for pills since few like needles and or the storage requirements of injectable Semaglutide. HOWEVER, this pill is ineffective both in terms of medicine and cost, unfortunately.
Several GLP-1 pills are in the pipeline, and there is near bottomless R&D budgets being spent on the area currently, but it isn't here yet and this isn't "it."
I'd strongly suggest people ignore this release, and keep using injectable Semaglutide/Tirzepatide.
To me, anyone who tried injections quickly gets over the needle anxiety, it's pretty easy and painless. I don't think the market is people switching from injection to pills (particularly if less effective), to me the market is in people who are too anxious to start injections but would use a pill.
You underestimate how deep anxiety for needles can be. I have a friend that has gotten regular injections for years and it still happens that he faints from it.
A total of 205 participants were randomly assigned to receive oral semaglutide, and 102 to receive placebo. The estimated mean change in body weight from baseline to week 64 was -13.6% in the oral semaglutide group and -2.2% in the placebo group (estimated difference, -11.4 percentage points; 95% confidence interval, -13.9 to -9.0; P<0.001).
At what would be $10/day – why's that ineffective?
Because if you compare it to the injection trial, you'll see even higher weight loss, and even lower side effects. We're also producing 25mg of oral medication for the same effectiveness as 2.4mg of injection; that doesn't make economic sense.
Novo Nordisk's own clinical trials (OASIS 4, OASIS 1 Vs, STEP 1). In order for oral Semaglutide to be effective you need to substantially increase the oral dosages for the same effect. Meaning you need more Semaglutide for the same action-of-effect, which increases side effects (+2.6% Nausea, +6.9% Vomiting, based on 2.4mg Vs. 25mg).
As I said above, this is being worked on (inc. by Novo Nordisk), but oral Semaglutide is a very naive early attempt. They got first to market, but that doesn't mean it makes sense for people who can handle injections; you cannot compare doses 1:1 because of how weak oral is, you need to compare action-of-effect. Once you look at effectiveness, oral costs more than injection.
"Counterfeit" is a tricky word when the Eli Lilly product in question isn't actually available for sale, meaning that nobody is selling anything purported to be a branded version. Nobody even knows yet what the Eli Lilly brand of retatrutide will be called. There isn't anything yet to counterfeit.
You're correct that the amino acid with the sequence YA¹QGTFTSDYSIL²LDKK⁴AQA¹AFIEYLLEGGPSSGAPPPS³ is being manufactured and sold. And people are justified in being wary whether the substance they get is actually a pure version of retatrutide. But it's not counterfeit.
It's an important distinction. Counterfeiters are by definition liars, and it's reasonable to assume that liars are cutting corners. But someone correctly manufacturing a specific amino acid is truthfully selling what they claim to be selling. It might turn out that retatrutide causes you to grow extra eyes in five years, and the FDA trials are on the brink of discovering as much, in which case Eli Lilly-branded retatrutide will never come into existence. For that reason it would be prudent to wait for FDA approval.
If bros are saying they're selling something manufactured by/for Eli Lilly, then yes, that's scammy. The chatter I've encountered has been clear it's gray market from China.
I really hope the addiction engineers at Frito-Lay, etc. don't figure out a good workaround for these wonder drugs.
There's a billion-dollar prize if you figure this out, and the food industry is already openly discussing it.
https://www.foodnavigator.com/Article/2025/07/22/glp-1-drugs...
Frito-Lay switching from Cheetos to protein bars still seems like a net win.
Yea, agreed.
I'm more worried there's some plausible way (like the ginger discussed) to negate the GLP-1 agonist's function itself or its net effects.
They're not going to talk about it in open industry journals, but Big Tobacco actually did do this with engineered high nicotine tobacco used to adjust addictivity levels.
https://en.wikipedia.org/wiki/Y1_(tobacco)#Legal_controversy
Interesting ginger is discussed.
The one thing I will literally eat an entire Costco sized pack of even while on my max GLP-1 dosage was Biscoff cookies. Not much else that I could "eat through" the drug when I was at my peak weight loss phase.
I've been on Zepbound and Wegovy, and n=1. It seems like the more complex the flavors (at least to me) the less appealing the food is.
So Doritos is too much. A butter or white cheese puffed corn snack tastes pretty good -- but I don't crave them.
> There's a billion-dollar prize if you figure this out, and the food industry is already openly discussing it.
Do you have any evidence of this? Your link doesn't confirm it.
Per my link above, it's just evidence they're reacting to it, but I suspect there are more nefarious things going on they're not posting in public trade journals.
The "prize" I'm referring to isn't a literal X-Prize for addiction haha, but I mean market share, etc. is very worth investing in this.
"There is a real risk, especially for brands that are slow to adapt."
Such insight! Of course that could be said about almost anything.
Hah! This website throws up a modal and blocks browser-native Copy Text functionality with both Ctrl + C and right click > Copy. Haven't seen that in a long time.
>The GLP-1 tsunami is approaching. As demand for weight loss drugs surges, some food and drink categories are set to decline sharply.
Defeated by either noscript or mobile's double-tap to select, copy.
I expect a second-order effect of cheap GLP-1s ending obesity will be to relieve the pressure on food manufacturers to make their products actually healthier
There are many other risks* than obesity from consuming UPFs, and we may find we've just removed the main stop-loss on worse outcomes
*Diabetes, all the biome/gut stuff which is getting better understood, colon cancer, etc etc
The thing about second order effects is that they are almost never larger than the first order effect.
Furthermore, GLP-1 users report having fewer cravings or just reduced appetite in general, whereas what you describe would require some sort of "calorie reduction pill" which would allow people to lose weight without altering their relationship to food. But that pill does not exist.
FWIW it exists: https://en.wikipedia.org/wiki/Orlistat
Hah! Thanks for the correction.
> The thing about second order effects is that they are almost never larger than the first order effect.
Sounds clever but this is just a labeling trick. When a second order effect is larger than the first order one, we just rename them to first order and intermediate effects.
For example, the first order effects of growing GLP-1 prevalence are actually consumption of prescription pads, new demand on pill bottles, and gas consumption of pharma sales reps.
The second order effect is weight loss in patients who take the drugs.
Cute and thus worthy of an upvote, but whenever I see scientists or economists refer to first or second order effects it pertains to things that are subsequent to each other in time, or at least intended vs. ancillary. I don't think anyone except for a Stafford "the purpose of a system is what it does" Beer acolyte would designate new demand of pill bottles as the first order effect of a new medication.
It's just something that statisticians have observed across many fields: you theorize about how potentially huge a particular interaction effect or knock-on effect could be relative to the main effect, you read about the Jevons Paradox and intuitively feel that it can explain so much of the world today... and then you get the data and it just almost never does. No reason why it couldn't, just empirically it rarely happens.
The demand for pill bottles literally does grow before anyone takes the medication, no?
And correct I agree they wouldn't designate the demand for pill bottles as the first order effect. That's because despite happening first, it's not the most important object of analysis. That's why it's a disproof of your earlier claim that second order effects aren't more significant than first order ones: because if they were, they'd be considered the first order effect.
> The demand for pill bottles literally does grow before anyone takes the medication, no?
Only really in the US. In most other countries they use blister packs instead. Global consumption of blister packs is so huge (not just for prescription medications, also OTC, vitamins, supplements, and complementary medicines), even a blockbuster medication likely only makes a modest difference to manufacturer demand in percentage terms.
> For example, the first order effects of growing GLP-1 prevalence are actually consumption of prescription pads, new demand on pill bottles, and gas consumption of pharma sales reps.
I take injectable tirzepatide prescribed by an electronic prescription… so impact on pill bottle demand and prescription pad demand in my case is literally zero.
And I doubt pharma sales reps have a lot of work to do selling GLP-1 agonists-who needs to convince doctors to prescribe a drug when there’s dozens of patients inquiring about it?
Yes the article is about pills, but most people are on injectables still (that may change over time). It likely has increased demand for needles and sharps containers. But in dollar terms, that’s a small percentage of the demand for the medication itself.
...
You are missing the point.
s/pill bottle/blister pack/
s/prescription pad/e-prescriber submissions/
All irrelevant to the convo :)
They are all irrelevant to everything, because in dollar and percentage terms they are a drop in the ocean
On the contrary, it may force them to make the products healthier. I've heard many GLP-1 users reporting an aversion to processed foods and cravings for healthy food.
I was thinking exactly this. People consume processed foods because they highjack our evolutionary responses. If GLP1 agonists make people immune to those high fat, big carb diets, perhaps we would see a decline of these strategies and instead seeing companies compete for the low appetite of people through smaller quantity yet high quality foods, rather than fast large quantity food.
This feels overly optimistic. You want to optimize for existing foods that are still high fat big carb and don't have the quality qualifier. I'm not familiar with the biological pathways that GLP1 operates on but I'm sure food companies will be working on adversarial products
My experience hasn't been aversion so much as just total apathy. The magic they once held is completely broken, and I'd rather eat real food.
Ancedata, but those around me on it seem to have a lower tolerance for fatty and oily food, also increased sensitivity to sugar.
Eating healthier for a while itself will reduce your palette for these foods, and make normal food taste better.
If you limit your sugar intake for a bit, American bread becomes quite the tasty treat.
It might not be direct action of the medication, but the medication making it easier to fix your habits can have huge dividends, similar to how giving an ADHD person stimulant meds make them less likely to die from misadventure or substance use because they self medicate less.
> UPFs
I think the current NOVA Classification for Ultra Processed Foods is flawed and often drops food containing preservatives and stabilizers into the same bucket as nutritionally poor items.
It also doesn't do a good job distinguishing value or health outcomes from consumption and simply lumps all UPFs into the same bucket. In otherwords fortified whole-grain breads and sodas are both UPFs but objectively they are not the same in terms of nutritional value or health outcomes.
The NOVA Classification's intent is to flag products where processing replaces whole foods, or adds cosmetic or functional additives to engineer taste/texture. It doesn't really factor in actual nutritional value or health outcomes from consumption.
We need to come up with a better system to identify to denote healthy or unhealthy foods, and also to identify foods that contain ingredients that have unknown impacts on our health outcome. Our current regulatory environment is to permit until proven harmful, so having something to flag x-factor ingredients would be beneficial.
> pressure on food manufacturers to make their products actually healthier
Probably not. Food manufacturing is not high margin. The things that would make "products actually healthier" are higher cost both in terms of inputs and in terms of shorter shelf life.
If people eat less and total sales volume decreases, there will not be additional money to change products lines. Expect corporate consolidation and a focus on children and glp-holdout populations, similar to cigarette manufacturers.
Similar to vapes, I could see the development of "ceremonial foods" that are chewed but not swallowed, like gum but with broader effects. Imagine something that approximates the experience of the crinkly bag, oily smell and physical crunch sensation of chips that then evaporates after the crunch. It would maybe even have a double bag for discretely spitting out the too small to crunch anymore shards of a saliva-phobic food grade meta-material.
They'll just make the food more expensive. It's something they've been doing for decades, sneakily.
I remember the YORKIE bar which had the letters of the name stamped on each piece (it was a segmented chocolate bar).
Eventually someone in my house noticed the stamped letters were gone, turned out they moved to a smaller bar with only 5 segments. It was hard to notice otherwise.
In practice, food manufacturers actually market "protein fortified" versions of products for GLP-1 users.
The idea is basically that doctors recommend you keep a high protein diet while on the drugs because a calorie deficit without protein will lead to muscle wasting.
> relieve the pressure on food manufacturers to make their products actually healthier…
Maybe, but with the new pressure of "people are eating less" to deal with.
Even if there are other poisons, eating less poison is still better than eating more poison.
”From 2013–2014 through August 2021–August 2023, the age-adjusted prevalence of obesity did not change significantly, while severe obesity prevalence increased from 7.7% to 9.7%” [1].
What fraction of America’s severely obese are being treated for it? (What fraction refuse treatment?)
[1] https://www.cdc.gov/nchs/products/databriefs/db508.htm
I would've expected that uptake was only beginning in 2022 and still vastly increasing through 2023 (plus the compounding loophole that allowed telehealth companies like Ro to really expand the target audience). 2024 and 2025 data are likely to be better telltales of the impacts of GLP-1s.
I've been thinking of trying GLP-1's since I have not been able to put off the extra weight I've gained since covid. I'm in my 30's now and I feel like around this age I am starting to feel the effects of this extra weight on my body.
What is HN's experience with using GLP-1 inhibitors, for those who have used them? I've heard of side effects like bone density loss, but I've heard those side effects are caused by taking too large of a dose.
Bone density loss is a side-effect of losing weight. GLP-1s cause you to lose weight. You counteract that the same way you counteract it during all weight loss: Each day, eat 0.36 grams of protein for each pound (lbs) of healthy or lean body weight (i.e. you don't need additional protein for your excess body-fat, so use lean/or hypothetically healthy weight). Exercise inc. resistance training. For example if you would be 180 lbs at a healthy weight for your height, eat minimum 65 grams of protein.
Both of the two available GLP-1 have similar side effects, with Tirzepatide being lower at an equivalent effect dose. Their common side-effects are: Nausea, vomiting, diarrhea, and indigestion. With rare serious side-effects being: Pancreatitis, allergic reaction. thyroid cancer, and acute kidney injury.
Generally speaking the common side-effects are dose-dependent. If you suffer too much, you back off the medication until the side-effects are at a level you can manage. This is common.
So basically eat a high protein diet and do some weight lifting, that doesn't sound too. Thanks for the insight.
I've been on a low dose for a year. I've lost 25kg (60 lbs) without much effort. Yes, it definitely dulls my appetite, and if I want to have a nice meal, I need to plan ahead for several weeks so that I have it _just_ before my next injection. There's also the fact that I didn't realise how important snacking was to my mental health. Since I don't have that, I've had to find other ways to boost my mood.
As a brief summary, it absolutely delivers what it says it does. I've lost weight as it claimed due to appetite suppression and feeling fuller longer. However, it's more complex than that, and the battle to ensure I get enough protein has been tough.
> Since I don't have that, I've had to find other ways to boost my mood
I have a similar issue, what did you come up with?
> I didn't realise how important snacking was to my mental health
Could you expand on this?
Not OP but eating is often used to distract or alleviate uncomfortable feelings like boredom, anxiety, etc.
The bone density and muscle wasting are a product of a calorie deficit without protein or weight training. You'll see the same effects without GLP-1s if you just diet and don't actually lift.
As confirmed by DEXA scans, I maintained my (very high) bone density and actually put on about 3lb of muscle over a 2-month period on low-dose GLP-1 + a GHRH, while losing about 16lb of my most stubborn fat, including visceral fat that I hadn't been able to crack. I'm in my 40s, and my routine includes weight training, a high-protein diet, and Brazilian jiujitsu.
My approach is minimum effective dose as an amplifier to a good diet and active lifestyle, and it's been pretty damn effective. Primary effects are an effortless relationship with food - the "itch" I used to feel to eat constantly is pretty much gone, and the psychological pain of not eating things is more or less nonexistent. I did a 36 hour fast just to push it a bit, and it was trivially easy.
Side effects include an elevated heart rate (~5-8bpm, in my case taking me into the low 60s at rest) and sweating all the time, both of which are almost certainly due to the glucagon agonist's thermogenesis effect. No problems with constipation, though stools are harder (comparable to those on a keto diet, in my experience). No particular ill effects otherwise. n=1, YMMV.
Constipation and nausea.
You won't want to eat much, and if you do try to eat a full meal (if for example you went out to eat) you'll feel like crap for a few days.
But yes, otherwise it works as advertised.
To be clear, that is the advertised effects, not the side effects. The idea is that if you over eat you feel terrible, but also you won't want to overeat since you'll be full.
> I have not been able to put off the extra weight I've gained since covid.
What have you tried ?
Intermittent fasting, lifting, calorie counting. The problem is that I am only able to stick to those maybe for a few weeks at a time before I get off track and end up back where I started. Except with weightlifting, I was able to stick with that for a few years, but unfortunately you can't outlift a bad diet. My relationship with food has never been a healthy one, and it's been that way ever since I wad a kid.
I highly recommend trying CBT. In particular the app Noom was excellent at (permanently) reframing my relationship with food.
I've never heard of that app before, I'll take a look at it.
Still ridiculously expensive. This sells for virtually nothing as a “research chemical.”
Reminds me of the markups on AZT back in the day.
It's an interesting industry that needs billions to bring a new drug to market. At the same time it creates a lot of value to a patient. But the manufacturing of a single dose is usually tiny.
Now how do you price that? The profits here will reward pharma investors and enable more investments in RnD of new medicines. I feel that's mostly fair.
Some types of software aren't too far from that paradigm.
The 'risk' here is often carried by publicly funded research. ~6.2 billion for glp
The private 'investment' comes in manufacturing, scale and marketing.
Novo Nordisk has spent 41% more on shareholder enrichment (buybacks and dividends) than on R&D over the past five years.
> Novo Nordisk has spent 41% more on shareholder enrichment (buybacks and dividends) than on R&D over the past five years.
So they are good stewards of their funds and know they can't deploy as much as they have? Berkshire Hathaway does the same thing.
Is Berkshire Hathaway able to monitize the output of government funded research as effectively?
The typical other solution for this is government grants for research.
It could work but there are problems in (1) the amount of money required and (2) the funding research -> getting votes pipeline is borked (credit assignment in general is borked).
Incentive is would be research forever without any results. See how expensive NASA programs were.
They went to the moon - that's not no results.
I'm assuming by “research chemical” you mean "counterfeit chemical" - Quite a signal for society, of individuals willing to inject themselves with these due to lack of funds or lack of effort.
That analogy would hold if a counterfeit dollar were perfectly identical to a real dollar, totally indistinguishable, and nobody could possibly tell the difference. Most of the "research chemical" drugs out there are chemically identical to the marked-up pharmaceutical products. Not similar, identical.
When you are buying chemicals from unknown entities you are adopting the enormous risks that come with it.
Drug synthesis can get very complicated. Purity of the drug is unknown.
Which contaminants are present and what are their effects on your body? Unknown.
What if any recourse do you have if they poison you? Minimal to none.
Even if you have a trusted third party doing efficacious testing of the compounds, the consistency of manufacture will be unknown unless they also do inspections. While I have no doubt that you can have private entity do a far better job than the FDA if the incentives are right there will be no business there. Perhaps a charity could work? I have no idea how though.
> Not similar, identical.
Without coming from the manufacturer or being validated by an independent, trusted third party, you do not know that the chemical composition is what is purported.
They are literally synthesized drugs that are not from the manufacturer.
They are synthesized drugs that are from a different manufacturer. (Usually synthesized the same way, via the same methods.)
If it's not misleading to buyers, it's not a "counterfeit".
I would say that it seems the vast majority of buyers on social media are convinced the drugs are coming from Eli Lilly & are being bought through "research" loopholes.
Not everything is counterfeit.
What is absolutely shocking isn't that we have a weird drug that finally makes you stop consuming too many calories. What isn't shocking isn't that you eventually lose weight by eating much less. What is absolutely shocking is that people are using it correctly; existing with heavy obesity can finally return to being a somewhat obscene life choice and not a cruel fate of luck.
Insurance companies should be paying people to take this considering the other costs it reduces.
You're missing the time aspect:
Obesity mostly causes expensive problems years later. People stay in their jobs for an average of something like 3-4 years. By the time anyone has an issue, it's the next guy's problem (or ideally, Medicare's).
They should. Unfortunately a lot of incentives are not aligned. Due to the profit cap as a percentage of premiums, generally higher medical spending increases health insurance profits rather than reducing them. It's the same thing with PG&E -- the only way for them to make more money is to increase costs. It's exactly the opposite of a normally functioning market, and you see the same result in both cases.
There are more powerful forces than the profit caps, namely that the big insurers now actually also own the doctors.
And capped or not, the pay-vider structure allows intra-company eliminations to bury arbitrary amounts of money as "not profit" even though it effectively is.
And even if that weren't true, the expected coverage term for a US patient is ~4 years due to it being tied to employment, so there is quite literally zero incentive to address any health issue that won't materialize as cost in the next few years (obesity being one such type of health problem).
> And capped or not, the pay-vider structure allows intra-company eliminations to bury arbitrary amounts of money as "not profit" even though it effectively is.
Source? There are 7 large publicly listed health insurers with public financials, all underperforming SP500 for more than a decade. There are myriad other non profits such as Kaiser/Cambia/Premera/Providence/various BCBS/etc, all with public financials as well.
Where is all this fraud going? And it’s happening across hundreds of executive offices across the country? And getting past 50 state insurance regulators that have to approve prices for insurance?
That would be remarkable levels of corruption and collusion.
It's not "fraudulent" per se, nor does it require corruption or collusion beyond what people already openly accept when they accept the existence of payviders (which they shouldn't! Or at least not for-profit payviders).
Payvider: An entity that is both a payer (insurer) and a provider (medical practice). Most payviders also have vertically integrated PBMs (pharmacy benefit managers), pharmacies, and labs, all of which participate in the same scheme.
A few of the examples you listed are NOT payviders, they're just payers, and therefore do not have these levers available to them.
Vertically integrated companies evade profit caps on their insurance division by shifting money to their unregulated provider, PBM, or labs divisions. It's pretty simple: the insurance arm overpays its own subsidiary doctors and clinics and records these internal transfers as mandatory "medical care" which is recorded as loss on the insurance side. The parent company then pockets the excess money as unrestricted profit on the provider/PBM/lab side, effectively bypassing the legal limit on how much insurance revenue they can keep and completely destroying the incentive to manage costs through their insurance division, at least when those costs originate from their own providers, which given that e.g. UHG is now the largest employer of doctors in the US, is increasingly often!
Is it fraudulent, corrupt, or collusive for a health insurer to employ doctors who deliver care? Not per se, but it gives insurers the ability to more or less arbitrarily convert premium dollars into profit while still getting people to defend them with claims like "they've been underperforming the SP500 for more than a decade."
Here are a few sources about different constituent behaviors, though you'd have to do a decent amount of reading to stitch together the full picture of how this works:
https://www.statnews.com/2024/11/25/unitedhealth-higher-paym...
https://www.healthaffairs.org/content/forefront/insurers-own...
https://www.wsj.com/us-news/unitedhealth-medicare-fraud-inve...
https://www.statnews.com/2024/07/25/united-health-group-medi...
> Vertically integrated companies evade profit caps on their insurance division by shifting money to their unregulated provider, PBM, or labs divisions. It's pretty simple: the insurance arm overpays its own subsidiary doctors and clinics and records these internal transfers as mandatory "medical care" which is recorded as loss on the insurance side. The parent company then pockets the excess money as unrestricted profit on the provider/PBM/lab side, effectively bypassing the legal limit on how much insurance revenue they can keep and completely destroying the incentive to manage costs through their insurance division, at least when those costs originate from their own providers, which given that e.g. UHG is now the largest employer of doctors in the US, is increasingly often!
Yes, UNH does better than the other managed care organizations because their healthcare business has higher margins than their insurance business. But it’s certainly not arbitrary, and it’s apparently not enough to make their shares worth buying.
More importantly, UNH competed against other insurers. They don’t get to “arbitrarily” pay their doctors (as if any business wants to overpay their employees). If they pay too much, then they will have to charge higher premiums. Premiums which also have to be approved by state regulators. And it’s a fact that UNH’s premiums are comparable to everyone else’s premiums. Why else would people buy from them?
>Is it fraudulent, corrupt, or collusive for a health insurer to employ doctors who deliver care? Not per se, but it gives insurers the ability to more or less arbitrarily convert premium dollars into profit while still getting people to defend them with claims like "they've been underperforming the SP500 for more than a decade."
The silly claim is stating managed care organizations are booking outsize profits, yet they don’t show up in 10-Ks or even shateholders’ pockets.
Underperformance relative to SP500 is a factual claim. 2% to 3% profit margin (objectively a tiny profit margin is a factual claim for 6 different businesses. UNH is at 5% to 7%, which is decent, but pathetic compared to tech/pharmaceutical/finance/real estate/oil companies.
Hopefully you can see why this all sounds like unfounded conspiracy theories. Just the fact that it’s better to own SP500 than a health insurer stock should be enough to conclude there are no “unrestricted” arbitrary profits being taken. They are very much restricted, and their shareholders know.
> Yes, UNH does better than the other managed care organizations because their healthcare business has higher margins than their insurance business. But it’s certainly not arbitrary, and it’s apparently not enough to make their shares worth buying.
UNH outperformed the S&P by a huge margin up until their Medicare Advantage fraud case pummeled the stock price a few months ago. https://www.alphaspread.com/comparison/nyse/unh/vs/indx/gspc
> The silly claim is stating managed care organizations are booking outsize profits,
Is this claim in the room with us now?
My claim is that the pay-vider structure enables these businesses to produce way, way, way more money than their regulatory "profit cap" leads people to believe. They can remove what would be profit from their insurance arm (where profit is capped anyway, so it keeps them under the cap) and dump it into their healthcare arm (proven by above-market self-reimbursement rates) to fund network expansion, which then further strengthens the insurance arm's market position (alleviating their need to "compete against other insurers" [ lol ])
Your claim is actually concordant with mine, which is that this profit doesn't show up as margin and doesn't show up as excellent stock performance. Correct! That's what it means to hide profit in order to stay below profit cap!
Anyway it's clear that I'm talking to a "stocks guy" who lacks the curiosity to actually understand how a business works beyond the 10-K (where all this stuff is discussed, by the way, you can find it euphemistically referred to as "network optimization").
Like I said, you'd have to do some reading well beyond the 10-Ks and the price chart lmao.
>Your claim is actually concordant with mine, which is that this profit doesn't show up as margin and doesn't show up as excellent stock performance. Correct! That's what it means to hide profit in order to stay below profit cap!
This definition of “hide profit” seems to be no different than “invest in the business”.
> which then further strengthens the insurance arm's market position (alleviating their need to "compete against other insurers" [ lol ])
Why is this “lol”? It is true that vertical integration results in efficiencies, and that can lead to lower premiums (not that it will absent sufficient competition). Kaiser has been doing it to much acclaim for almost 100 years.
I hadn't thought about the 4 year aspect. That is a great insight. I am against the current US healthcare system in general but I wonder if decoupling healthcare from employment (slightly) could help. Maybe employers should be required to pay for coverage that an employee selects? (clearly a lot of hand waiving of the exact mechanism here but..) This would incentivize healthcare plans to actually compete for someone to sign up with them and to give them an incentive to keep that person healthy since they would likely stick around longer with them.
> It's the same thing with PG&E
An electric and gas utility is a structural monopoly, you cannot run multiple power wired and gas pipes to each property.
Health insurance is easily switched. If Kaiser spends too much, then Anthem/United/Aetna/Cigna/etc can gain customers by offering a lower price.
I think their desired cash flow direction is: customers should be paying to take this in order to avoid the punitive deductible for being overweight.
The ACA makes it illegal for insurers to make the “punitive deductible” a function of one’s probability of needing healthcare, hence the financial incentive is for the insurer (who can bring down cost of claims, and hence be able to sell insurance at lower premiums).
Of course, the insured has the quality of life incentive of not having to deal with complications from consuming excess calories.
The incorrect assumption here is that insurance companies want costs to be reduced.
They don't.
Because despite being labeled as not-for-profit, they will always scale up their "cost" to match their revenues, and live on the 1-2% difference.
They want the absolute nominal dollar values for care to be as high as humanly possible.
I love the two claims about health insurance companies: simultaneously denying coverage for needed healthcare, and "scaling" up their healthcare costs to increase profit.
There's no inconsistency in those statements, because there are also for-profit health insurance companies (that deny coverage) and not-for-profit ones (that balloon costs)
Is that what you meant?
That premise must be invalid because if true, no one would buy insurance from for profit insurance companies. Their prices are all basically the same, approved by the same state government employees.
Plus the out of pocket maximums are a pittance compared to what complicated healthcare costs can be, so paying more for premiums to ensure you are not denied coverage would be a no brainer.
Alas, that is not the case, so the reality must be different from the premise.
Also, here's a non profit health insurance company denying coverage:
https://www.theguardian.com/us-news/2024/sep/29/louisiana-ho...
https://lailluminator.com/2025/04/12/blue-cross-2/
None of that invalidates what I said as a general rule for health insurance company behaviors that are also very well documented in media, so I'm not sure what you're trying to clarify for me here.
> That premise must be invalid because if true, no one would buy insurance from for profit insurance companies.
What premise? That companies balloon costs or aim to provide less care if they can get away with it? It's a complete non-sequitur if you think so.
This premise:
>because there are also for-profit health insurance companies (that deny coverage) and not-for-profit ones (that balloon costs)
The claim that for profit health insurance companies deny coverage to save money and non profit health insurance companies balloon costs to maximize healthcare expenses is obviously wrong (as demonstrated in previous comment).
The claim that health insurance companies in general both deny coverage to reduce healthcare expenses and maximize healthcare expenses to increase profit is obviously wrong, because it's inherently contradictory.
>behaviors that are also very well documented in media
I don't see any documentation of this behavior. The documentation that does exist is the whole business limps along on a knife's edge, lagging SP500, while have no power to set their prices (the government has to approve their prices). They certainly do engage in outsourcing and underemployment, perhaps to intentionally delay and deny care, but probably leading to just as many incorrect approvals as incorrect denials (obviously you won't hear about the former in the media).
The for-profit ones have capped profits as a percent of costs(e.g. 80-20% rule). Therefore, game theory predicts they support costs increases that are industry wide (raise all boats), and oppose them when only the company is impacted (lose market share or profit).
I wouldn't be surprised if this paves the way for differing insurance rates on health markers given how magical glp-1s seem to be, and how much of modern disease is based on lifestyle factors.
The amount of ingredient in the pill is huge relative to the shot, and you need to take it daily...which shows how hard it is to get drugs into the body.
Real question: given the dosage, how would you go about getting the pill and liquefying it? That would provide a huge, cheap supply of semaglutide.
If you start a GLP-1 drug, how do you ever stop?
Seems like GLP-1's are not a cure but treat the symptoms. You need to keep treating the symptoms forever unless you solve the issue.
It's not really different than losing weight by any other method in that respect.
There is always the risk of regaining weight unless you continue to do whatever caused you to lose weight (e.g. restricting calories) to some extent.
I guess a "cure" would be good but since we don't have one having to periodically go back on glp drugs if you gain weight is no different from periodically having to go on a diet if you gain weight.
On the other hand most people tend to naturally gain weight pretty slowly (e.g. a pound a year) so having to go on glp drugs for a period every few years wouldn't even be that bad, especially if they're available in pill form.
> how do you ever stop?
By not taking it.
> Seems like GLP-1's are not a cure but treat the symptoms
This goes against all of the evidence around rebound, improved diet and exercise after folks have lost weight, et cetera.
It is mixed. It can be a cure for some people. Last time I looked my impression it seemed like about half the people has only moderate rebound or less.
You have a lot of results that look like this, with an average bounce rebound of 2/3s of the loss.
https://pubmed.ncbi.nlm.nih.gov/35441470/
However, detailed analysis usually shows a bimodal distribution, with people who maintain or even lose more, and those that go back or even gain relative to baseline.
Treating the symptoms can be helpful in the long term if symptoms are a contributing cause to the disease. I used to ride my bike 150+ miles a week, but after not being able to do so for a bit due to other reasons I gained some weight. At the level of riding I was doing, an extra 20-30 lb of weight makes riding far less pleasurable, particularly when it comes to going uphill or on dirt paths.
Just finding 10-12 hours in which to exercise every week is challenging on its own. It's much more difficult when the exercise itself becomes harder and less rewarding.
At 150$ a month this is tempting, but I'm worried it's going to cause cancer or something.
I fear the same thing but then people that know more about this say that these GLP-1 drugs have been used for many years (by diabetics) so they aren't untested or un-studied.
Don't know how accurate that is, though.
> Don't know how accurate that is
Literally from the Wikipedia article: “In 2002, Eli Lilly partnered with Amylin to develop exenatide and secure approval to market the drug. Exenatide's 2005 approval by the U.S. Food and Drug Administration showed that targeting the GLP-1 receptor was a viable strategy and inspired other pharmaceutical companies to focus on that receptor” [1].
[1] https://en.wikipedia.org/wiki/GLP-1_receptor_agonist
There is a minor risk that a new drug causes cancer or something. However, obesity is a major risk for very large amount of health problems, including many cancers.
Obesity has a known, well established, multi-modal cancer risk, and then on top add metabolic syndrome (T2, heart disease, etc).
So, you're weighing a hypothetical risk against and establish risk, and concluding that the unknown risk is scarier than the known risk. Which is irrational.
Imagine if someone asks you if you want to take the "obesity pill," and you looked at the side effects objectively. But instead you weight obesity as "normal" and this as "new and scary."
To be completely honest I don't 100% trust the medical industry whenever there's so much money behind marketing something. There's a very real vested interest in trying to downplay the risk factors because let's just say tomorrow they found out this stuff makes all your teeth fall out.
A whole lot of folks would lose billions of dollars. My first instinct is to think I need to go and take another Europe. The food is better there and I lost a good amount of weight the first time.
Understood. You may be interested to learn that Liraglutide, a GLP-1 Agonist, has been commercially available and commonly used since 2010 (15-years+) without any unknown/unexpected additional side-effects appearing. It was developed in 1998.
The main reason GLP-1 Agonists are suddenly more popular is two things:
- Liraglutide had to be taken daily, instead of weekly.
- Nobody every paid for Liraglutide to be clinically approved for weight-loss. It was an anti-diabetic medication; but the mechanism of action is the same.
Compared with liraglutide, semaglutide was engineered mainly with a longer, differently attached fatty-acid side chain that increases albumin binding and slows clearance, so it lasts longer; both drugs activate the GLP-1 receptor.
To be fair, if this stuff did make your teeth fall out, that would still be worth it.
Everything is risk calculus. If you're just a bit overweight, then yeah probably not worth the risk. If you're morbidly obese then it's a no brainer.
I will say this: the bar for obesity is lower than most people think.
Nah, you'll just be on it for the rest of your life. Drug companies prefer chronic illnesses since they cannot be cured, and recipients take the drug for life. All these hormones (GLP, testosterones, hrt) will need to be taken forever. Very few people come off GLP-1 and keep weight off.
But how many of those people would have ever lost the weight in the first place without GLP-1?
I mean, obesity is a chronic illness, so is hypogonadism. If your balls don't work they don't work.
Chronic illnesses require chronic medication. The same is true even WITHOUT the medication. If you're obese and want to lose the weight, you need to manage your diet and exercise. Forever. Until the day you die. You can't ever stop that or you'll be obese again.
Some things just don't have one-time solutions, and that's okay.
Maybe not.
https://news.ycombinator.com/item?id=46348199
> Drug companies prefer chronic illnesses
Gilead has made bank on Solvadi, a drug that cures a previously-chronic disease [1].
> Very few people come off GLP-1 and keep weight off
Rebound can be close to 100% if you’re severely obese, but for most people it’s much less [2]. (Everyone I know who was taking it two years ago is off it, and they eat and exercise healthier than they did.)
[1] https://en.wikipedia.org/wiki/Sofosbuvir
[2] https://pubmed.ncbi.nlm.nih.gov/35441470/
So far they proved to do the opposite.
Obligatory reminder that this pill is much less effective than Zepbound, not to mention reta.
That might be okay! I'm on the lowest dose of Zepbound (tirzepatide), 2.5mg, and I'm losing 5lbs a week, which is almost too much. It will be helpful to switch to something perhaps not as good in pill form (versus my weekly injections) once I reach my target weight. For those who need pill form and the effectiveness available, it's a slam dunk imho. Orforglipron [1] (small molecule by Lilly vs a peptide) will be potentially available shortly for those needing more effectiveness. We're making incremental improvements in this system rapidly.
HN Search: orforglipron - https://hn.algolia.com/?dateRange=all&page=0&prefix=false&qu...
Could also be great for maintenance dosing. I'm reaching the end of my ~weight loss journey~, and it's not a sure thing that the insurance company will continue paying for the injections once I'm no longer overweight.
I'm definitely willing to keep taking it. If insurance won't pay for it, I could pay for the pill out of pocket if I had to, which would be cost prohibitive for the injections.
5 lbs a week is crazy? Are you expecting asymptotic approach to healthy weight? I'm 185 and would prefer to be more like 170, but 3 weeks seems too fast.
I started at 170lbs and my target is 135lbs (early 40s male). My blood panel looks good per my PCP, and as long as I'm not losing weight so fast I have excess skin or I experience liver, kidney, or pancreas failures of any degree, that meets my success criteria. I am trying to shed as much unhealthy visceral fat as possible while using the pharma intervention to dissuade me from unhealthy consumption habits.
At $300/month cash pay through https://lilly.com, I find the ROI to be exceptional.
135lbs seems very low for an adult male. How tall are you? Why is that your target?
While I think BMI is fairly suboptimal and would defer to a DEXA scan, that weight puts me right in the middle of a healthy BMI for a human of my gender, height, and age. As mentioned, I lift weights, three days per week. This also increases my metabolism and daily caloric budget (beyond basal and resting metabolic rates).
My goal is to drop fat, gain muscle, and be strong with good cardio performance, and a GLP-1 turns off the part of my brain that made me carry excess unhealthy fat and eat the foods that made that fat. GLP-1s also promote thermogenesis, so it is turning on the switch to tell your body to burn fat that you would have to fast or get into ketosis via a ketogenic diet otherwise to get into (by first depleting your glycogen reserves). I do not get any fatigue such that I would when fasting or on a keto diet needed to encourage thermogenesis and burning up fat reserves, which is awesome imho.
My brain says "you are fine" instead "you must eat, feel hungry, and get hangry, even though you already have all of this fat." A bug has been patched.
https://pubmed.ncbi.nlm.nih.gov/?term=glp-1+thermogenesis
(think like a hacker, the body is just another system to hack)
Interesting. I also do weightlifting 3x/week and my weight is in the 190s (male, 60yrs old, 6' tall). I am definitely carrying some excess fat but think my ideal would be somwhere around 175-180. Have never done any BMI tests.
> 135lbs seems very low for an adult male
Impossible to characterize without height.
Well, that's why I asked how tall he was...
He said "right in the middle of a healthy BMI" which would make him 5'2" or 5'3".
> 5 lbs a week is crazy?
https://www.nutrition.gov/topics/healthy-living-and-weight/s...
"A reasonable rate of weight loss is 1 to 2 pounds per week."
Going too fast has downsides.
https://health.clevelandclinic.org/risks-of-losing-weight-to...
That's starvation level weight loss. A normal regime would be more like 1-2lbs per week via a moderate calorie deficit.
Even if you water fasted, you would not lose 5 lbs a week sustained. It was probably your first week and mostly water weight
It depends on your starting weight. If you weigh north of 300lbs than this is very much possible for several month.
2.5kg per week? Wow.
Indeed, I have to make a conscious effort to remember to eat, and consume 800 calories (two servings) of Creamy Chocolate Soylent (premade, liquid bottles) daily, along with fiber gummies to keep everything moving in my digestive track. I do strength training to preserve muscle mass. Desire to eat anything sweet or alcohol has gone to zero (RIP my craft beer desires and my sweet tooth).
How long did those effects take to come into effect? I have been on 2.5 for a week and haven't noticed a change in my appetite, though I have lost 2 pounds.
First week. You might need a higher dose, check with your prescriber. My partner needed to go to 5mg to see improved results, but dropped back down due to side effects (which I did not have).
You are consuming only 800 calories a day? From a starting weight of 170ish?
Was this plan made with your doctor?
My doctor does not approve or reject my actions, they simply make recommendations and provide guidance. I work with people who understand my risk appetite, which is aggressive. If you are not aggressive as a practitioner, I will work with someone who is. Unsophisticated humans need protection, which I understand and appreciate, but I need coaches and subject matter experts who will push me to my limits.
Indeed; there is a MASSIVE market demand for pills since few like needles and or the storage requirements of injectable Semaglutide. HOWEVER, this pill is ineffective both in terms of medicine and cost, unfortunately.
Several GLP-1 pills are in the pipeline, and there is near bottomless R&D budgets being spent on the area currently, but it isn't here yet and this isn't "it."
I'd strongly suggest people ignore this release, and keep using injectable Semaglutide/Tirzepatide.
To me, anyone who tried injections quickly gets over the needle anxiety, it's pretty easy and painless. I don't think the market is people switching from injection to pills (particularly if less effective), to me the market is in people who are too anxious to start injections but would use a pill.
You underestimate how deep anxiety for needles can be. I have a friend that has gotten regular injections for years and it still happens that he faints from it.
> have a friend that has gotten regular injections for years and it still happens that he faints from it
It could be an anxiety. I developed one after a nasty blood draw. When someone pointed out it was an anxiety response, it sort of just went away.
Yeah its very much anxiety. He's a wreck when he has to get it done. He is fully aware but it doesn't matter, the physical response is too strong.
I mean… https://pubmed.ncbi.nlm.nih.gov/40934115/
A total of 205 participants were randomly assigned to receive oral semaglutide, and 102 to receive placebo. The estimated mean change in body weight from baseline to week 64 was -13.6% in the oral semaglutide group and -2.2% in the placebo group (estimated difference, -11.4 percentage points; 95% confidence interval, -13.9 to -9.0; P<0.001).
At what would be $10/day – why's that ineffective?
Because if you compare it to the injection trial, you'll see even higher weight loss, and even lower side effects. We're also producing 25mg of oral medication for the same effectiveness as 2.4mg of injection; that doesn't make economic sense.
> We're also producing 25mg of oral medication for the same effectiveness as 2.4mg of injection; that doesn't make economic sense
Plenty of people can’t or won’t inject. And plenty of people don’t need 2.4mg injected.
The pill is cheaper to make, distribute and take. That seems to make economic sense to me.
> this pill is ineffective both in terms of medicine and cost
Source?
Novo Nordisk's own clinical trials (OASIS 4, OASIS 1 Vs, STEP 1). In order for oral Semaglutide to be effective you need to substantially increase the oral dosages for the same effect. Meaning you need more Semaglutide for the same action-of-effect, which increases side effects (+2.6% Nausea, +6.9% Vomiting, based on 2.4mg Vs. 25mg).
As I said above, this is being worked on (inc. by Novo Nordisk), but oral Semaglutide is a very naive early attempt. They got first to market, but that doesn't mean it makes sense for people who can handle injections; you cannot compare doses 1:1 because of how weak oral is, you need to compare action-of-effect. Once you look at effectiveness, oral costs more than injection.
> you need more Semaglutide for the same action-of-effect
Sounds not ineffective.
> oral costs more than injection
Are these being marketed to the same populations?
Its still effective though and there is no oral form of the other GLPs as of yet.
Reminder that Reta has yet to actually hit the market, and social media is flooded with counterfeit resellers.
"Counterfeit" is a tricky word when the Eli Lilly product in question isn't actually available for sale, meaning that nobody is selling anything purported to be a branded version. Nobody even knows yet what the Eli Lilly brand of retatrutide will be called. There isn't anything yet to counterfeit.
You're correct that the amino acid with the sequence YA¹QGTFTSDYSIL²LDKK⁴AQA¹AFIEYLLEGGPSSGAPPPS³ is being manufactured and sold. And people are justified in being wary whether the substance they get is actually a pure version of retatrutide. But it's not counterfeit.
It's an important distinction. Counterfeiters are by definition liars, and it's reasonable to assume that liars are cutting corners. But someone correctly manufacturing a specific amino acid is truthfully selling what they claim to be selling. It might turn out that retatrutide causes you to grow extra eyes in five years, and the FDA trials are on the brink of discovering as much, in which case Eli Lilly-branded retatrutide will never come into existence. For that reason it would be prudent to wait for FDA approval.
I would say that it seems the vast majority of the social media buyers think they're buying the drug from Eli Lilly.
So maybe I'm grammatically and formally incorrect. But a lot of this feels very scammy.
If bros are saying they're selling something manufactured by/for Eli Lilly, then yes, that's scammy. The chatter I've encountered has been clear it's gray market from China.