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.
> 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.
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).
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.
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.
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.
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.
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?
"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 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.
> 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
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.
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.
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.
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.
If it's not misleading to buyers, it's not a "counterfeit".
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).
> 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.
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.
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.
Even if you water fasted, you would not lose 5 lbs a week sustained. It was probably your first week and mostly water weight
2.5kg per week? Wow.
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.
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?
> this pill is ineffective both in terms of medicine and cost
Source?
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.