Ozempic-style drugs now in trials for heart failure, addiction and even aging
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–All of heart failure, addiction, and aging certainly have inflammation and redox stress as substrate.
It's interesting that GLP-1 agonists all have pulmonary effects. There's GLP-1 receptors in the lung.
(the lung is somewhat relevant in redox stress / burden / balance
as well as neuroendocrine metabolism. the lung is a metabolic organ. it metabolizes serotonin. serotonin has… many roles, anciently repurposed for a ton of things.)
It's usually the case that anything that, say, curbs addiction? will curb inflammation and redox stress, and have pulmonary effects. Exercise, for one. Psychological safety. Healthier eating. 5-HT2A agonists. NMDA antagonists. And… GLP-1 agonists.
spooky old-man-oracle voice: everything is pulmonaaaaryyyy
I look at the obesity epidemic, the efficacy of GLP-1, and wonder if the GLP-1 was once part of our body chemistry and, somehow, no longer is.
Or is the GLP-1 just a "magic bullet" that luckily works in a way to overcome our selfish desire to overeat unhealthy foods—there are other, non chemical, reasons we have been getting obese as a society over the past decades?
I've been on GLP-1 for a few months now and it is amazing. And I've been wondering this whole time—why did I previously have this "food noise" that, apparently, people like my wife do not? (Example: she'll often stop eating and say, "I'm full" when I'm thinking, that doesn't happen to me unless I eat an insane amount. Where is my I'm full detector?) I was sure thin as a rail for the first three decades of my life. Is it just a male, aging thing? ... I'm just flummoxed (but happy to be losing weight finally even if I do have to pay out of pocket every month for the drug).
Now, if you remove breads, sugars, and processed foods, try eating the same number of calories with whole foods only. You’ll become full way before you reach that number.
And some people, like your wife, simply respond to food differently. Id say she’s in the minority, though.
I, like yourself and most people, don’t feel full until I’ve eaten an unreasonable amount of certain types of foods. Since switching to Whole Foods and cutting out breads, sugars, and processed foods, I’ve lost weight while eating until I’m full/satisfied.
I've not found any promising leads, besides maybe something fuzzy about intestinal microbiome. But I've not given up hope of figuring it out.
Especially, I'd note that if a food production company had accidentally added, say a GLP-1 antagonist (without knowing what it was) to their product, they'd just notice sales go up and consider it quite good business.
It's hard to estimate how much the last couple of generations weight was because of smoking cigarettes suppressed appetite too
Yes?
When you hit the puberty your requirements go up for an additional 1000-1500 calories.
Women calorie demand returns back after puberty, men stays the same and the calorie burn rate (if you don't sit 24/7 at the screen ofc) are higher than a women' one in the first place. So you on all levels - including your own habits - are conditioned to eat a whole lot.
And then your forties come your body suddenly decides what you don't need that much energy and your metabolism slows down, winding down the calorie intake demands. But if all your life you needed a whole chicken with a plate to 'feel full' then you won't suddenly eat a couple of chicken wings and have a 'feel full' feeling.
And I would agree with a sibling comment: the food caloric density did increased a lot though 'saltier, sweeter, and generally more addictive' is not a rule but a more of a diet choices.
So while your body produces it in a few places, the product gets used up almost immediately.
I got off of them after 14 month and while it hasn’t been as easy as being on them for sure, my time on them gave me a chance to look at what I was eating and how much I was eating more subjectively. I lost nearly 40 lbs, put ten back on before leveling out.
Critical to add - losing the weight allowed me to become much, much more active without pain so I attribute a lot to that habit of being really active being picked up to my maintenance.
YMMV
I take it for ASD related food noise, and it's incredible.
I suspect it’s a touch more complex than that. :)
Anecdata: I have a 40-something friend who enjoys eating lots more than I do (and I witness this repeatedly: round after round of bread and chunks of cheese after a full meal, always happy to have desserts that I’ll sometimes forgo, etc.) and who stays slim. Sure, he exercises, but not so much more than I do to account for the calorie delta between us.
He’s just made differently, in a way we can’t currently explain. We sometimes joke about a faecal transplant.
Its strange to think what you want is a less efficient food processing engine. That society has so many calories to burn that we can reduce our ability to reduce caloric intake by 30%, but I would like that. And a fecal transplant might be a good start.
One of the worst outcomes from GLP-1 drugs are people getting on them and then saying ridiculous things like this. Just totally confident that they can discount other folks lived experiences.
I know quite a few skinny people who have struggled every single day with food noise, overeating, and self control. They simply got through it with a lot of struggle, habits, and discipline.
Some of these people had to maintain their weight and fitness because their careers required looking conventionally attractive for their jobs. It consumed most of their life doing so. Some of these folks are now on GLP-1s and their lives are immensely better as they don't need to constantly be in a battle of willpower with themselves.
There are a huge number of "skinny" people out there who feel hunger in very likely the same way many obese people do.
You're right, but the charitable interpretation of GP's comment is that people that were always skinny don't feel hunger, which clearly isn't true in a strict sense, but not totally untrue either, it just isn't as often.
What you're talking about seems to be people that worked their way to being skinny, or those that have such low body fat that they have visible abs, which even 'naturally skinny' people would struggle to maintain.
As someone skinny enough to have visible abs (But not washboard abs either), I don't try particularly hard to maintain my weight, it's mostly just avoiding obvious things like having fast food all the time (I still do eat it) and working out. Food isn't something I think about unless I'm hungry, and despite working in offices stocked full with candy/snacks, it hasn't resulted in weight gain over my tech career. I've been told directly by people in my circle (Not in tech) that they would really struggle with working in an environment like that.
I know a few folks on GLP-1s, and they operate on a completely different wavelength in regards to food than I do, and it's been great to see them reach their body goals.
If GLP-1 blockers work for people then great, but it does so by making them uninterested in eating, meaning all those years of people being demonized for saying obesity is, in some meaningful part, a lack of will power and self control were indeed right. If it was either of those, and instead obesity is a purely genetic condition, appetite suppression wouldn't help.
What if staying skinny requires willpower... but the genetics determine whether little willpower is enough, or you need astronomical amounts of willpower?
That isn't a moral judgement or a knock against the person, we all have issues we struggle with.
That makes no statement over a measurement of willpower required though, and I don't know of any research linking dietary willpower to genetics. That link could exist, but if it does I don't think we have found it yet and that argument hinges on pharmaceuticals being able to overpower genetics, which is a bold claim.
I specifically didn't say people with self control issues specific to diet are bad people for it, or lazy, or whatever you may be reading into it. Everyone has shit they deal with, that's expected not a reason to ostracize a person.
My point remains, if GLP-1 blockers help a person lose weight they haven't been able to lose then great, I hope it leaves them healthier and happier. And also, the fact that a diet suppressant did the trick makes it pretty clear a lack of self control was at play since the fix was finding a way to eat less.
as a skinny person for most of my life, and someone who wakes up famished in the mornings, very eager to eat breakfast, this is patently false.
but I do agree that it's a miracle cure for those who struggle with constant hunger.
I am also reading up on things called triple agonist but its not readily available in Canada. Web sites with a lot of discussion about peptides and titrating which seems a little difficult.
Folks really only discontinue because of cost … which is because our health system is a disaster
I'm assuming this is normal and something will happen when I up the dose.
Even 10mg is very, very high, beyond the trials maximums (though preliminary small escalation trials tested that, even reaching 16mg, I guess the participants really didn’t enjoy that) and would have serious side effects if not result in a hospital visit as well.
Please be a lot more careful dispensing advice on a public forum on matters where people could get hurt.
The triple agonists like Retatrutide should be available in ~6 months assuming all goes well with their trials. Unless you are Trump who got special permission to get it before everyone else! https://www.statnews.com/2026/06/23/eli-lilly-unusual-weight...
But as the dosage climbs, so does the price. I started at the $300/month dosage and am up to the $350/month dosage.
(Hopefully I get to my target weight at this dosage—it's very possible.)
Now all we need is an easy pill that makes you hate opioids.
One weird aspect of it working as well as it has on me is that when I see people who are morbidly obese in public now I have to fight the urge to proselytize GLP-1.
The potency and purity are typically pretty good but from time to time vendors will be outed for either outright fraud or a bad batch that is underfilled or low purity. Most of the direct vendors (out of China) will guarantee fill and purity, and also give credit on your next order for lab test costs if you share the tests with them for future marketing purposes.
All sorts of risks involved of course, but you can mitigate them fairly effectively. Your risk tolerance may vary. Some folks will buy single vials from US resellers and trust those seller's lab test reports. Others (smartly, imo) don't trust that and do their own testing directly on the product they receive.
This grey market supply chain is remarkably robust these days. Plenty of suburban Facebook soccer moms organizing group buys.
"Person A takes Foundayo, Person B takes mystery drug?"
Not sure what you think you're learning from that.
Not about to try and get some first hand experience with that tho!
recents topics:
The Truth About BPC-157 & Peptides
Retatrutide & Beyond: Eli Lilly Exec on Next-Gen GLP-1s
Retatrutide Phase 3 Results: What the Data Actually Means
It is now firmly back, after ~6 months off the drug (due to cost) :/
I've managed to keep off the lost weight, through a lot of willpower, but winter will be a struggle I can tell.
It wasn't until this week that I started feeling the effect, and so far, it's like...yeah. I don't feel this damn near constant urge to eat anymore.
It's so frustrating to deal with people who naturally eat sensibly and look down on overweight people and accuse them of not having self-control. They have a complete lack of empathy and assume that everyone else has the same properly-calibrated sense of hunger that they do. Guess what: not everyone does.
They have no idea what it's actually like. They'll eat a six-inch sub sandwich and feel full all the way to dinner. Maybe they'll eat a handful of nuts in the afternoon if they get snackish. Then they assume that's what life is like for me.
No. If I ate just the six-inch sandwich, my stomach wouldn't even tell me I'm satiated, let alone full. I'd have to eat the footlong. And I'd still be hungry two hours later. Yeah, I'd eat a handful of nuts. And then another. And another. Until eventually I've eaten 700+ calories from nuts and I'd still be fucking hungry.
And don't tell me "drink more water!". If anything, I was overhydrating. My urine was nearly clear and I'm pissing every hour.
Ozempic has flipped the switch, though admittedly I'm in a transition period for sure. I went out for dinner the other day, had a bowl of soup and only about 1/3rd of my main course. My stomach was feeling full, but something was still telling me to keep eating. Luckily the discomfort of fullness won out and I took the rest home. The next day, for lunch, I ate the leftovers, and I felt full afterwards, and didn't feel the urge to snack at all before dinner.
It's such a breath of fresh air. Is this what normal or "naturally thin" people experience? Hunger that reflects actual caloric needs, rather than some unnecessary urge to constantly keep adding things to the stomach?
EDIT: "It is now firmly back, after ~6 months off the drug (due to cost) :/"
That sucks. With my insurance, it's only $50 for a 4-week supply, but on the prescription form from Costco, it lists the "U/C" as $2,207, which my understanding means it would be $2,207 if I didn't have insurance.
The price of this drug is damn near criminal.
The looking down on people is the huge problem. It is at least in part a self control problem, and also who cares? Everyone has things they try to deal with, faults they don't even notice, etc.
In my opinion, saying it is often a self-control problem is calling a spade a spade. It isn't always that, there are other reasons people may struggle with obesity. But for those finding help in GLP-1 blockers it does seem to boil down to just eating less. And again, who cares? Demonizing and shaming people for lacking self-control in certain areas is just a pretty shitty way to treat people.
I've come to realize that some of this difference actually comes from low-effort activity like walking.
At 1796 kcal BMR your weight is 76 kg.
At 1896 kcal BMR your weight is 86 kg.
At 1996 kcal BMR your weight is 96 kg.
It is easier to just eat 100 kcal less, but it's also not unreasonable for people to walk more. 100 kcal gets burned in something like 30-60 minutes of walking.
And that 100 kcal is a 10 kg difference in weight in the long-term (22 lbs). The key is that people usually don't go for those walks to lose weight, they just happen naturally during their day due to other reasons.
Now, who knows, without the walking I might have been 10 pounds heavier, but it sure didn't bring my weight down.
The only thing that did (in my eight years of recording) was eating less.
I had to prepare for surgery some 7 or so years ago and started eating the smallest of meals out of fear that I might die before the operation could take place (I had a constriction in my intestinal tract that, if blocked, could cause my intestines to burst).
In that two months of fear and small portions I lost like 20 pounds.
In the 7 years since though, I have been unable to stay at the small portions. (Until Zepbound.)
But then I took the pill (orforglipron) and the kilograms started disappearing.
You don't get the full calories from nuts because we're can not chew them so thoroughly that they're 100% bio-available. There were studies that confirmed it. Now, eating them as butter, that's another thing.
700+ calories of nuts is about 100g-150g?... it would be better if you ate them in one sitting, the satiety suppression would be stronger. And don't be afraid to eat them, as much as you want, as long as they're whole, with no coatings. Just don't washed them with Coke, juice, etc.
Good news: they let the patent on Semaglutide lapse in Canada, and it’s already expired naturally in India and a bunch of South American countries. There are going to be accessible generics at some point.
If you ever tried water fasting first couple of days are gruelling but day 3 and 4 are significantly easier. Another natural hunger suppressant is cardio which reduces hunger.
The hunger never went away.
It can also increase it! Both effects are scientifically plausible
These include things like loading your body earlier in the day with heavy protein and fermented foods, eating proteins and vegetables before carbs (make less room for carbs), and of course there is still the lower stress, improve sleep and exercise.
I'm not suggesting these are replacements, but potentially like a micro-dose response.
These GLP 1 drugs are huge molecules with a GLP 1 shaped key on them. It's like a house key attached to a school bus. Once it's in your lock, that key is going to be a pain to remove.
Stimulating natural GLP 1 helps for a few minutes. Using these drugs can help for a week.
I did try keto before. Heavy protein, low carbs. Everyone promised a high protein/fat/fiber diet with low starch/sugar was the secret to feeling full sooner and for longer.
Nope. Didn't change a damn thing. I was still hungry all the time.
My experience mirrors the GP. Ozempic really flipped the switch. See my other comment (https://news.ycombinator.com/item?id=50399564) for more.
I don't really like fermented foods and I avoid dairy. Only have heavy carbs a few times a month. Mostly it's meat, vegetables, fruit. I've done various diets as a result of trying to fix other issues but none move the needle on the food noise
I've also had no stress for like, a year now due to my circumstances
On a glp I don’t need to carefully plan my diet because carb-heavy or greasy foods are unappealing to consider. It’s a very strange feeling for me to look at a big menu and realize I want to order the salad, not that I “should”, and my cholesterol levels fell by 66%
This is basically about as far as I feel like entertaining conspiracy theories. I think it's a fairly grounded one, compared to most.
Not claiming that a molecule or a class of such molecules (or a perfect storm of unrelated molecules acting indirectly) is behind the obesity epidemic, or that there's explicit malicious intention involved, just that it does make me wonder.
Yes! It's sugar. And yes, it's highly addictive.
I propose that it's less about the molecule and more about the receptor, and the heuristically self-balancing system and the novel environment it finds itself in.
sugar
I find the treatment that got approved for its effect on hunger last year interesting. It's a completely different drug to semaglutide and its analogs. Quick search suggests that it's seemingly not as effective for ordinary obesity, but substantially more effective for this specific syndrome, and vice versa.