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
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.
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?
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.
Yes, it’s a miracle cure. It makes you realise the almond milkers were just lying to you the whole time. It’s not about willpower, it’s about them not having that condition. Skinny people don’t even feel hunger.
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.
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.
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.
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.
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
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.
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 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...
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.
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.
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 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.
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.
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.
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.
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?
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.
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.
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
What naturally is supposed to produce GLP-1 in our bodies ?
Eating high satiety foods
https://www.hsalist.org/tools/satiety-index/
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.
2 replies →
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?
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.
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.
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, it’s a miracle cure. It makes you realise the almond milkers were just lying to you the whole time. It’s not about willpower, it’s about them not having that condition. Skinny people don’t even feel hunger.
> 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.
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.
> 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.
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.
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.
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
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.
2 replies →
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 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.
1 reply →
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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.
> 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.
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.
4 replies →
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.
1 reply →
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.
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
1 reply →
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.
1 reply →
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.
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.
You might find Slime Mold Time Mold's "A Chemical Hunger" interesting: http://achemicalhunger.com/
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?
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.
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.
Legalizing weed was an inside job to sell WeGovy! Kidding, but the timing is a touch funny.
> could there be a molecule that does the opposite?
Yes! It's sugar. And yes, it's highly addictive.
There are plenty of medicines that cause people to gain weight. Corticosteroids are notorious for increasing hunger leading to weight gain.
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