It's interesting with GLP-1 agonists that they all curb inflammation and redox stress.
–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
Curious layman—is it possible that something in our environment has changed in the past several decades such that our bodies natural GLP-1 is not responding/present?
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).
I personally don’t think it’s that complicated. I think it’s simply just the result of caloric density increasing as foods become engineered to make us want more. They’re saltier, sweeter, and generally more addictive. You can eat 2,000 calories in a sitting and not “feel full.”
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.
Stomach size is probably a massively under appreciated factor. If you naturally have a smaller build, you’ll likely have a smaller stomach, and that sense of being full will arrive much sooner.
Based on my experience fasting (as a huge guy) stomach size fluctuates quite a bit and is mostly conditioned on your eating habits. There have been times in my life where I could finish off a large pizza myself. These days I feel stuffed after one or two slices and a breadstick regardless of how little I’ve eaten during the day. Days I eat less I find I can eat less later. If I have breakfast (usually only ever on vacation) I can eat more later in the day before feeling full.
I agree there's a range but - arm chair doctor here - believe that a bigger abdominal cavity leaves more room for that expansion, so bigger people are able to expand their stomach to a larger size before pain and discomfort.
I've had similar ideas for a while. That there's either a blocker of GLP-1 in our modern environment or something that previously produced or triggered production is missing.
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.
We live in a world of constant stress and noise and demands and (subtle and less subtle) violence and power games in basically all our relationships. No wonder our balance can only be (somewhat) restored by introducing massive amounts, either of “food” or “highly concentrated substances” like drugs. The village around us is out of balance, and burning, and so are we. Nowhere is (emotionally) safe, our nervous systems run on high intensity survival mode 24/7.
> I was sure thin as a rail for the first three decades of my life. Is it just a male, aging thing?
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.
It's also possible that there has been an environmental or dietary "weight gain" effect for a really long time, but previous generations were counteracting it with cigarettes
It's hard to estimate how much the last couple of generations weight was because of smoking cigarettes suppressed appetite too
It's important to remember that the natural GLP 1 you produce is a very very different molecule than GLP 1 agonists. The body uses natural GLP 1 in minutes. These drugs attach a very complex molecule to the GLP 1 site, allowing it to stay active there for hours.
So while your body produces it in a few places, the product gets used up almost immediately.
That link is great, but putting jelly beans above peanuts makes zero sense to me, anecdotally. I can’t argue with the numbers/science but peanuts are something I reach for often when I’m looking to feel full, they are really great for that.
Does GLP-1 help someone who eats because of boredom? My ADHD riddled brain seeks constant stimulation, so when there's nothing to do it turns to food even though there's no hunger or cravings. If I'm occupied with something, I can easily skip food and go on an extended fast, hunger suppression has never been a problem. But it's hard to stay occupied all the time, would GLP-1 help in such a case?
Absolutely did for me. Boredom, stress, and general food noise all the time. I never felt sick, just felt like I finally had control over when I wanted to eat. I still felt hungry but never uncontrollably.
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.
They may curb the initial impulse, or they’ll quickly teach you that you feel a bit unwell (eg low-key nauseous) if you eat too much or badly when you’re on them. Either way, probably the same outcome.
I don't know how useful this is, but what I found helped is simply not buying things you'd want to eat in-between meals. At least for a little while, long enough to break the habit. After a month or so of your brain craving something and not finding anything suitable in the kitchen, you'll lose this impulse.
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.
I suspect a persons microbiome has a lot to do with how they process food.
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.
>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.
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.
Yes, there are outliers in just about any situation. The vast majority of healthy people, though, do not have this food noise impulse. If they did, they'd not be healthy people.
This is an absurd claim. Skinny and fat isn't an indication of whether a person experiences hunger.
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?
We may be talking about different issues. If a pharmaceutical intervention drastically reducing hunger allows a person to low weight, it confirms that the issue was eating too much.
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.
Of course if you eat less and less, at some moment you stop gaining weight. The question is what else also happens to you.
Before physiological harm, such as losing your muscles and ultimately your heart muscles, there will be psychological harm, when your hunger prevents you from thinking clearly, so you may become e.g. unable to hold your job.
I am saying this because sometimes "just eat less" is a technically correct answer to losing weight, and yet...
(And the pill breaks the link between the amount of food and how the person feels about it.)
Oh I 100% agree. I think people may be making a mistake taking an appetite suppressant and watching pounds drop thinking it means they're healthy.
The question rarely asked in modern medicine is why a symptom is present. Doctors and patients almost entirely focus on how to get rid of the symptom, in this case dropping lbs without first understanding why the weight is there.
I equate GLP-1s to simply eating less because my understanding of the mechanism is that is all it does, make a person uninterested, and even in some cases unable, to eat more.
Where do morals come into this thread? Obestity isn't a moral question, neither is self-control.
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.
It totally solved my food addiction. It flipped it like a switch - I knew what most people are like, where food isn't a thought every 15 minutes. What a glorious time. So much free head space
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.
> 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.
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.
>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.
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.
Not to argue with you—but walking has been a part of my regimen for a decade now (twice a day—after breakfast and dinner, FWIW) and there has been no obvious weight loss (I record it twice a week in Apple's Health app—have been for 8 years now).
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.)
I do not even use a car or mass transit. Every day I walk 40 minutes by foot to work in the morning, and 40 minutes by foot to home in the evening. Yet I couldn't lose a single kilogram.
But then I took the pill (orforglipron) and the kilograms started disappearing.
> 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.
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.
This may or may not have worked for you but I’ve found a lot of people just don’t give their bodies enough time to adjust to caloric deficit, it takes a couple weeks.
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.
I'm sure it works for some folks, but for those of us with "the little fat dude in our head", the hunger never goes away. The drugs work wonders, though. Cardio definitely always just made me more hungry even after 1-2 months of race training.
Ive never found cardio to suppress hunger. If anything I end up eating more after a large workload (fuel the afterburn i suspect). That said there are certainly lots of stabilizers from cardio…. Maybe if i was in a study id see a reduction in snacking or something..
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.
I'm curious if you've tried any methods to increase your endogenous GLP-1 activity?
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.
Natural GLP 1 is an extremely different molecule to these drugs. Natural GLP 1 gets used in minutes. It's like a house key. It fits in the lock, and it's easy to remove.
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.
GP here, yup, was about to write something like that.
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
I’ll add, I did keto and found I lost weight and was relatively able to control hunger, but my food choices were very narrow and everything needed careful planning, additionally my cholesterol and blood lipids went up a concerning amount, enough that my doctor recommended medication.
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%
I'm going to say something brave and controversial (/s), and I'll accept the downvotes and flagging: I don't believe you. I don't believe keto (or keto-ish) didn't lead to lower hunger cravings. Maybe you're missing some things from your story? maybe you're misremembering some things?
For those who may have tried other variants... is there a big difference between Ozempic/Wegovy/Mounjaro? My doctor prescribed WeGovy but my insurance does not cover it - my spouses does. However Mounjaro is covered by both insurances. Is it worth (effectiveness) switching to Mounjaro? I heard it is a 'double agonist' - what exactly does that mean?
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.
I've lost 28 lbs on Mounjaro in about 3-4 months. One injection per week, self-administered, completely painless. No more 6-8pm food cravings. That's on top of the money I save vs. eating out all the time (spending maybe $500-600 less per month than I used to, vs. $800 every 6 months for the medicine itself, without insurance). YMMV if you cook at home a lot, but I consider it one of the best lifestyle decisions I've made in recent memory.
Mounjaro is the more effective option of the 3 anyway so if that’s your goal and it’s covered, go with it. Double agonist means it targets two hormone pathways.
I was on mounjaro for 6-8 months and no regrets. I was offered the 3 alternatives, and was explained the efficacy of mounjaro so went with that one. No reported downsides other than sulphur burps but I think that’s universal.
It works quite well. I have a ton of friends that have lost a ton on it. But the main benefit is the health side. My blood sugar with not just the the weight loss is back to normal.
Folks really only discontinue because of cost … which is because our health system is a disaster
Wegovy has a pill, super convenient if you don’t want to prick yourself with an auto injector every week, but requires a 30 minute fast every morning and might be less effective. Also, the pills travel better since they don’t require refrigeration. I pay out of pocket with an HsA around $330/month on Amazon.
Ya, you are still ramping and the smaller doses are to see if there will be problems before you hit 30mg. You should notice something when you hit 10mg though.
30mg is an extremely high dosage, far beyond the maximum Semaglutide (Wegovy) trials (which initially topped out at 2.4 and years later validated a new max of 7.2) and likely to land you in a hospital.
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.
Ozempic and wegovy are a much more primitive drug and gave me worse side effects. Mounjaro is significantly better and proven to be more effective. Ozempic is cheaper though.
I had a lot more success and less side effects on Zepbound vs Wegovy. I pay out of pocket for Zepbound through Lily Direct and even with a coupon it's $500 a month. Without the coupon it would be $2k a month! It's worth it for me, though even though it hurts my wallet.
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...
!! I will check that out. I used to use Amazon pharmacy and it was $700 a month so I switched to Lily Direct which was $200 cheaper. Thanks for the tip.
These drugs are a godsend for so many (me included, on retatrutide) but especially for those of us here in America - legal environment broad enough to get them, relatively wealthy enough to afford them, and notably fat enough to benefit from them. The diffusion of this technology through the US might well increase American lifespan in a notable way.
Now all we need is an easy pill that makes you hate opioids.
Zepbound has been a godsend for me—trying unsuccessfully to lose weight for two decades now…
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.
Small peptide suppliers make them. You order by generic identifier & compound yourself. My identical twin & I are running an exponent: I'm on foundayo, he's on retatrutide. I'm down about 10 lbs. he's down 35.
Real gamble, that. You're injecting something that no regulatory body that said was safe and that that supplier is giving you what they say they are? Just like injecting whatever it is they happen to give you?
If you're doing this sort of thing, usually you batch your orders together (ideally with some friends) and randomly lab test a few vials selected from the large batch you receive. The powder form vials you receive before mixing will last more or less indefinitely in a freezer, so you can order multiple years worth of supply at a time.
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.
No, you can know that decisions are stupid before knowing their outcome. In fact, decisions can be stupid even when they result in a neutral or positive outcome.
Are you asking if we're learning about the general population, or about ourselves? We're 100% identical twins with nearly identical blood work across a fairly deep blood panel. We're learning precisely what we need to know to maximize efficacy for us.
There is an injection for opiods that works for a month at a time. It really annoys me because we’re still giving people methadone every day even though this injection exists.
Anecdotaly: at least for some GLP-1 initially seems to work by curbing appetite. But many seem to find their was around it by going for the most caloric foods before the feedback kicks in and sheer habituation/plowing through.
If a molecule can downregulate (downmodulate?) cravings so effectively, could there be a molecule that does the opposite?
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.
Processed food companies have been trying to find that for the last century and they've largely succeeded without specifying any particular molecule. You know Pringles chips?
Thanks for the link, haven't heard of this disease before. Sounds absolutely miserable. At least the root cause is a clear one.
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.
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.
It's interesting with GLP-1 agonists that they all curb inflammation and redox stress.
–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
Curious layman—is it possible that something in our environment has changed in the past several decades such that our bodies natural GLP-1 is not responding/present?
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).
I personally don’t think it’s that complicated. I think it’s simply just the result of caloric density increasing as foods become engineered to make us want more. They’re saltier, sweeter, and generally more addictive. You can eat 2,000 calories in a sitting and not “feel full.”
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.
Stomach size is probably a massively under appreciated factor. If you naturally have a smaller build, you’ll likely have a smaller stomach, and that sense of being full will arrive much sooner.
Based on my experience fasting (as a huge guy) stomach size fluctuates quite a bit and is mostly conditioned on your eating habits. There have been times in my life where I could finish off a large pizza myself. These days I feel stuffed after one or two slices and a breadstick regardless of how little I’ve eaten during the day. Days I eat less I find I can eat less later. If I have breakfast (usually only ever on vacation) I can eat more later in the day before feeling full.
I agree there's a range but - arm chair doctor here - believe that a bigger abdominal cavity leaves more room for that expansion, so bigger people are able to expand their stomach to a larger size before pain and discomfort.
I've had similar ideas for a while. That there's either a blocker of GLP-1 in our modern environment or something that previously produced or triggered production is missing.
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.
We live in a world of constant stress and noise and demands and (subtle and less subtle) violence and power games in basically all our relationships. No wonder our balance can only be (somewhat) restored by introducing massive amounts, either of “food” or “highly concentrated substances” like drugs. The village around us is out of balance, and burning, and so are we. Nowhere is (emotionally) safe, our nervous systems run on high intensity survival mode 24/7.
Yep; Things make much the same sense to me.
This paper is… I can't unsee it?: Aggression, Social Stress, and the Immune System in Humans and Animal Models – https://www.frontiersin.org/journals/behavioral-neuroscience...
serious paper, serious authors. Frontiers In is sometimes considered unserious? This is the real stuff.
Unserious tho: I lo-o-ove the Hideo Kojima-esque Friedman Brain Institute that one of the author is affiliated with, haha. <3
> I was sure thin as a rail for the first three decades of my life. Is it just a male, aging thing?
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.
It's also possible that there has been an environmental or dietary "weight gain" effect for a really long time, but previous generations were counteracting it with cigarettes
It's hard to estimate how much the last couple of generations weight was because of smoking cigarettes suppressed appetite too
What naturally is supposed to produce GLP-1 in our bodies ?
It's important to remember that the natural GLP 1 you produce is a very very different molecule than GLP 1 agonists. The body uses natural GLP 1 in minutes. These drugs attach a very complex molecule to the GLP 1 site, allowing it to stay active there for hours.
So while your body produces it in a few places, the product gets used up almost immediately.
Keeping that in mind then, what processes do produce the (short lived) GLP 1?
It is produced naturally by the intestine and brain stem when food is present. It happens in response to fats, proteins, and carbs.
Eating high satiety foods
https://www.hsalist.org/tools/satiety-index/
That link is great, but putting jelly beans above peanuts makes zero sense to me, anecdotally. I can’t argue with the numbers/science but peanuts are something I reach for often when I’m looking to feel full, they are really great for that.
Does GLP-1 help someone who eats because of boredom? My ADHD riddled brain seeks constant stimulation, so when there's nothing to do it turns to food even though there's no hunger or cravings. If I'm occupied with something, I can easily skip food and go on an extended fast, hunger suppression has never been a problem. But it's hard to stay occupied all the time, would GLP-1 help in such a case?
Absolutely did for me. Boredom, stress, and general food noise all the time. I never felt sick, just felt like I finally had control over when I wanted to eat. I still felt hungry but never uncontrollably.
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
They may curb the initial impulse, or they’ll quickly teach you that you feel a bit unwell (eg low-key nauseous) if you eat too much or badly when you’re on them. Either way, probably the same outcome.
I don't know how useful this is, but what I found helped is simply not buying things you'd want to eat in-between meals. At least for a little while, long enough to break the habit. After a month or so of your brain craving something and not finding anything suitable in the kitchen, you'll lose this impulse.
100% and if you have any snack type things you already bought you should do a full pantry clear out of all the crap.
Yes. But not fully. You will have less noise, most likely, which is enough to hopefully teach yourself different habits.
I take it for ASD related food noise, and it's incredible.
yes. source: it me
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> Skinny people don’t even feel hunger.
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.
I suspect a persons microbiome has a lot to do with how they process food.
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.
> Skinny people don’t even feel hunger.
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.
>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.
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.
Yes, there are outliers in just about any situation. The vast majority of healthy people, though, do not have this food noise impulse. If they did, they'd not be healthy people.
This is an absurd claim. Skinny and fat isn't an indication of whether a person experiences hunger.
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.
It is not necessarily either-or.
What if staying skinny requires willpower... but the genetics determine whether little willpower is enough, or you need astronomical amounts of willpower?
We may be talking about different issues. If a pharmaceutical intervention drastically reducing hunger allows a person to low weight, it confirms that the issue was eating too much.
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.
Of course if you eat less and less, at some moment you stop gaining weight. The question is what else also happens to you.
Before physiological harm, such as losing your muscles and ultimately your heart muscles, there will be psychological harm, when your hunger prevents you from thinking clearly, so you may become e.g. unable to hold your job.
I am saying this because sometimes "just eat less" is a technically correct answer to losing weight, and yet...
(And the pill breaks the link between the amount of food and how the person feels about it.)
Oh I 100% agree. I think people may be making a mistake taking an appetite suppressant and watching pounds drop thinking it means they're healthy.
The question rarely asked in modern medicine is why a symptom is present. Doctors and patients almost entirely focus on how to get rid of the symptom, in this case dropping lbs without first understanding why the weight is there.
I equate GLP-1s to simply eating less because my understanding of the mechanism is that is all it does, make a person uninterested, and even in some cases unable, to eat more.
Whew, lots of moralizing to unpack here.
Where do morals come into this thread? Obestity isn't a moral question, neither is self-control.
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.
> Skinny people don’t even feel hunger.
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.
That impulse you feel in the morning, imagine you felt it every half hour for the rest of your life.
I hear you. That's what i agree it's a miracle drug!
It totally solved my food addiction. It flipped it like a switch - I knew what most people are like, where food isn't a thought every 15 minutes. What a glorious time. So much free head space
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.
I just started Ozempic about 4 weeks ago.
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.
> 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.
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.
>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.
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.
Not to argue with you—but walking has been a part of my regimen for a decade now (twice a day—after breakfast and dinner, FWIW) and there has been no obvious weight loss (I record it twice a week in Apple's Health app—have been for 8 years now).
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.)
I do not even use a car or mass transit. Every day I walk 40 minutes by foot to work in the morning, and 40 minutes by foot to home in the evening. Yet I couldn't lose a single kilogram.
But then I took the pill (orforglipron) and the kilograms started disappearing.
> 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.
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.
This may or may not have worked for you but I’ve found a lot of people just don’t give their bodies enough time to adjust to caloric deficit, it takes a couple weeks.
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.
I'm sure it works for some folks, but for those of us with "the little fat dude in our head", the hunger never goes away. The drugs work wonders, though. Cardio definitely always just made me more hungry even after 1-2 months of race training.
I did keto for 9 months and was also doing cardio and resistance training.
The hunger never went away.
Ive never found cardio to suppress hunger. If anything I end up eating more after a large workload (fuel the afterburn i suspect). That said there are certainly lots of stabilizers from cardio…. Maybe if i was in a study id see a reduction in snacking or something..
> Another natural hunger suppressant is cardio which reduces hunger
It can also increase it! Both effects are scientifically plausible
> The price of this drug is damn near criminal.
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.
In the U.S. — it might be 6 or 7 years away (I was told by a pharmacist).
I'm curious if you've tried any methods to increase your endogenous GLP-1 activity?
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.
Natural GLP 1 is an extremely different molecule to these drugs. Natural GLP 1 gets used in minutes. It's like a house key. It fits in the lock, and it's easy to remove.
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'm not the GP, but I can answer this.
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.
GP here, yup, was about to write something like that.
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
I’ll add, I did keto and found I lost weight and was relatively able to control hunger, but my food choices were very narrow and everything needed careful planning, additionally my cholesterol and blood lipids went up a concerning amount, enough that my doctor recommended medication.
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%
I'm going to say something brave and controversial (/s), and I'll accept the downvotes and flagging: I don't believe you. I don't believe keto (or keto-ish) didn't lead to lower hunger cravings. Maybe you're missing some things from your story? maybe you're misremembering some things?
For those who may have tried other variants... is there a big difference between Ozempic/Wegovy/Mounjaro? My doctor prescribed WeGovy but my insurance does not cover it - my spouses does. However Mounjaro is covered by both insurances. Is it worth (effectiveness) switching to Mounjaro? I heard it is a 'double agonist' - what exactly does that mean?
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.
I've lost 28 lbs on Mounjaro in about 3-4 months. One injection per week, self-administered, completely painless. No more 6-8pm food cravings. That's on top of the money I save vs. eating out all the time (spending maybe $500-600 less per month than I used to, vs. $800 every 6 months for the medicine itself, without insurance). YMMV if you cook at home a lot, but I consider it one of the best lifestyle decisions I've made in recent memory.
Mounjaro is the more effective option of the 3 anyway so if that’s your goal and it’s covered, go with it. Double agonist means it targets two hormone pathways. I was on mounjaro for 6-8 months and no regrets. I was offered the 3 alternatives, and was explained the efficacy of mounjaro so went with that one. No reported downsides other than sulphur burps but I think that’s universal.
It works quite well. I have a ton of friends that have lost a ton on it. But the main benefit is the health side. My blood sugar with not just the the weight loss is back to normal.
Folks really only discontinue because of cost … which is because our health system is a disaster
Wegovy has a pill, super convenient if you don’t want to prick yourself with an auto injector every week, but requires a 30 minute fast every morning and might be less effective. Also, the pills travel better since they don’t require refrigeration. I pay out of pocket with an HsA around $330/month on Amazon.
I'll add that Zepbound is the same as Mounjaro, I believe (both add tirzepatide to the basic Ozempic/Wegovy drug).
I started wegovy 3 weeks ago (1.5mg oral dose) and so far have felt absolutely nothing, good or bad.
I'm assuming this is normal and something will happen when I up the dose.
Ya, you are still ramping and the smaller doses are to see if there will be problems before you hit 30mg. You should notice something when you hit 10mg though.
30mg is an extremely high dosage, far beyond the maximum Semaglutide (Wegovy) trials (which initially topped out at 2.4 and years later validated a new max of 7.2) and likely to land you in a hospital.
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.
Oral Wegovy is dispensed in higher doses than injection presumably because uptake via the gut is lower.
Yeah, came here to say you can't compare dosages across drugs—they are in some cases an order of magnitude different.
I misremembered the dosage, it’s 25 mg, not 30 mg. It’s pretty standard for oral, since absorption is different from injection.
Ozempic and wegovy are a much more primitive drug and gave me worse side effects. Mounjaro is significantly better and proven to be more effective. Ozempic is cheaper though.
I had a lot more success and less side effects on Zepbound vs Wegovy. I pay out of pocket for Zepbound through Lily Direct and even with a coupon it's $500 a month. Without the coupon it would be $2k a month! It's worth it for me, though even though it hurts my wallet.
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...
Whoa, thru amazon pharmacy you can get it for 300 after the $200 Lily coupon FYI.
Zepbond is $300/month from the pharmacy (CVS) as well… with the Lily coupon.
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.)
!! I will check that out. I used to use Amazon pharmacy and it was $700 a month so I switched to Lily Direct which was $200 cheaper. Thanks for the tip.
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These drugs are a godsend for so many (me included, on retatrutide) but especially for those of us here in America - legal environment broad enough to get them, relatively wealthy enough to afford them, and notably fat enough to benefit from them. The diffusion of this technology through the US might well increase American lifespan in a notable way.
Now all we need is an easy pill that makes you hate opioids.
Zepbound has been a godsend for me—trying unsuccessfully to lose weight for two decades now…
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.
How are you getting retatrutide? Are you in a trial? How is it working for you?
Small peptide suppliers make them. You order by generic identifier & compound yourself. My identical twin & I are running an exponent: I'm on foundayo, he's on retatrutide. I'm down about 10 lbs. he's down 35.
Real gamble, that. You're injecting something that no regulatory body that said was safe and that that supplier is giving you what they say they are? Just like injecting whatever it is they happen to give you?
If you're doing this sort of thing, usually you batch your orders together (ideally with some friends) and randomly lab test a few vials selected from the large batch you receive. The powder form vials you receive before mixing will last more or less indefinitely in a freezer, so you can order multiple years worth of supply at a time.
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.
Profoundly stupid shit.
Risky. Not necessarily stupid. I wouldn’t do it. But we’d have to observe the injury rate before being able to conclude anything.
No, you can know that decisions are stupid before knowing their outcome. In fact, decisions can be stupid even when they result in a neutral or positive outcome.
What's the experiment?
"Person A takes Foundayo, Person B takes mystery drug?"
Not sure what you think you're learning from that.
Are you asking if we're learning about the general population, or about ourselves? We're 100% identical twins with nearly identical blood work across a fairly deep blood panel. We're learning precisely what we need to know to maximize efficacy for us.
I'm saying that the "retatrutide" test subject has no way to access known-good retatrutide.
Supposedly narcan does that. Instead of after an overdose, if you have narcan administered beforehand, opioids are no fun.
Not about to try and get some first hand experience with that tho!
No, it blocks the effects of opioids, but it doesn't remove the cravings or withdrawal
And it only lasts minutes.
There is an injection for opiods that works for a month at a time. It really annoys me because we’re still giving people methadone every day even though this injection exists.
Anecdotaly: at least for some GLP-1 initially seems to work by curbing appetite. But many seem to find their was around it by going for the most caloric foods before the feedback kicks in and sheer habituation/plowing through.
if you want to hear endocrinologists talk with researchers and other qualified professionals about this space, I highly recommend this podcast.
https://docswholift.com/
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
If a molecule can downregulate (downmodulate?) cravings so effectively, could there be a molecule that does the opposite?
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.
Processed food companies have been trying to find that for the last century and they've largely succeeded without specifying any particular molecule. You know Pringles chips?
> could there be a molecule that does the opposite?
Yes! It's sugar. And yes, it's highly addictive.
You might find Slime Mold Time Mold's "A Chemical Hunger" interesting: http://achemicalhunger.com/
There are plenty of medicines that cause people to gain weight. Corticosteroids are notorious for increasing hunger leading to weight gain.
https://en.wikipedia.org/wiki/Prader%E2%80%93Willi_syndrome
Thanks for the link, haven't heard of this disease before. Sounds absolutely miserable. At least the root cause is a clear one.
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.
Fun!
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.
>could there be a molecule that does the opposite?
sugar
Legalizing weed was an inside job to sell WeGovy! Kidding, but the timing is a touch funny.
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