What Ozempic does to the gut-brain axis

https://www.psychologytoday.com/au/blog/mood-by-microbe/202606/what-ozempic-does-to-the-gut-brain-axis

209 520 25 days ago

I'd take them even if they didn't make me lose weight - and I'm the type of person that doesn't like takeing Tylenol unless absolutely necessary.

The best way I can describe it: my body and mind are no longer is in starvation mode. I plan, do, act and sleep well.

diggerboy• 25 days ago

Did you have to reach a certain dose for such effects?

chadd• 25 days ago

the minimum dose of monjaro (2.5mg injection once/week) can often be enough

barake• 25 days ago

Semaglutide does an incredible job of keeping my autoimmune issues in check. The only side effect I've had is needing to drink more water or else I feel like I've got the flu. Minimal tradeoff IMO

npunt• 25 days ago

oh say more?

spbaar• 25 days ago

Thirst affects me in a different way too. My throat doesn't feel dry and uncomfortable because before it reaches that point I almost get naseous.

faangguyindia37• 25 days ago

I remember reading the Hazada paradox, where they found these Hadza tribe members who live an active life, walking miles, hunting, and doing all physical labour, have the same maintenance calories as a Western person.

So where does the energy burn in a sedentary population come from vs highly active Hadza tribe members?

Pontzer’s research showed that while the Hadza were highly active, they actually demonstrated lower baselines of certain markers of metabolic and physiological stress over time compared to Western populations.

Don't quote me on this; I am paraphrasing things I remember from.

faangguyindia37• 25 days ago

my body and mind are no longer is in starvation mode

What does it mean? If a drug reduces your desire to eat food, wouldn't it also decrease your desire to eat food beneficial for your body?

I think the effect most people want is to stop craving junk food but still eat nutritious food required for muscle growth and health.

ceejayoz8• 25 days ago

What if you could intentionally eat good food?

I've heard it widely described as reducing mental noise around food.

sublinear4• 25 days ago

If you want the real answer, people suck at shopping for groceries and don't know how or want to cook.

Long before LLMs, there was a different but similarly misguided hype around making food more convenient. Making money off ignorance is not "innovation", but we live in a world convinced by arrogant and pretentious fearmongering liars.

As always, just do it yourself. It's not that hard after all.

kube-system9• 25 days ago

It does which is why medically supervised weight loss with GLP1s includes diet recommendations to mitigate this.

But in my experience, decreased cravings make it easier to choose food rationally. The food noise that causes people to overeat usually doesn’t cause them to overeat healthy foods anyway.

solumunus2• 25 days ago

Specifically for me it makes junk food unpleasant. My diet is now impeccable. I hardly ever have a takeaway and if I do it needs to be something that is not greasy and is good clean food.

I also find drinking alcohol much less pleasant. I still drink sometimes but after a few beers or glasses of wine it starts to become very unappealing and I stop.

I do bodybuilding and I’m still getting my 150g of protein in.

I’m barely overweight and I’m losing weight very slowly but I’ve decided I’m likely to stay on GLP’s long term, if not forever, just because the lifestyle changes have been so incredibly good.

Perhaps this helps dispel the myth that GLP drugs inherently = relentless starvation.

planckscnst• 25 days ago

You don't desire to brush your teeth (at least not in the way that you desire to consume calorie-dense foods). But you manage to still do it anyway. (maybe not you specifically, but people in general) You can make the same choice about nutrition. The lowered desire makes it easier/possible to do this

lrasinen• 25 days ago

My personal experience is like getting eye glasses for your appetite. Easier to eat reasonably sized portions and they're nutritionally well-balanced.

Also the late night cravings are more specific: instead of vague "need to eat something", it's "I'd love a tomato" or "mmm yogurt" or "actually a load of carbs would hit the spot".

seanmcdirmid• 25 days ago

You lose your appetite but can still shove things in your pie hole. You just have to make an effort to shove vegetables and protein in, rather than making an effort resist eating junk food.

raffael_de3• 25 days ago

considering what we have been learning about the importance of a working gut brain axis I'd be highly worried about Ozempic harming this connection.

dmayle3• 25 days ago

I had the same experience, but not with GLP-1 drugs, but by upping my protein intake to about 0.7g per pound of body weight.

Night and day, stopped always being hungry... I've tried Noom before (eating highly filling, low calorie foods, but filling, not satiating), but that only worked while I was tracking (and always forcing myself to keep it up)...

Losing weight required work on top of that, but the protein just made my hunger response start working properly again.

sublinear4• 25 days ago

I had a similar experience bringing down my A1C.

People talk a lot about meat, but not enough about dairy. My prayers were answered at the altars of feta, greek yogurt, half and half, butter, cottage cheese, etc. They made salads not suck. They opened up a ton of lower carb dessert options. My gut health improved. All of my health improved.

I no longer treat these humble foods as optional extras. They perfectly fill the gap in my daily protein needs. They were never unwelcome, just forgotten.

magicalhippo• 25 days ago

I recall reading a metastudy of EU studies about 10 years ago, where they focused on three different diet classes: calorie counting, low carb, high protein.

Calorie counting diets had no restrictions on what they ate, as long as the participants didn't exceed the calorie target.

Low carb (Atkins) had no calorie restriction but had to restrict carbs.

High protein also didn't have calorie restriction but participants had to ensure at least 20% of the calories in meals were proteins.

They found that while all helped people lose weight, only the high-protein made it stick reliably.

I used that as basis for my own weight loss and it worked very well for me. As you said it made me full in a different way. YMMV.

teliosix4• 25 days ago

I have lost 30lbs this year and even the difference between .5 and .7 is noticeable to me.

There is also the variable that you can work out too much. I did a brutal 30 minute glycolytic conditioning session on Friday and it just doesn't matter how much protein I consume the next day. Something with ghrelin goes off the chart and the next day takes huge will power to not just eat everything.

I think it is even worse with max effort weight lifting.

jawilson2• 23 days ago

I had the same experience, but with a strict keto diet, <20 net carbs / day. I started in 2014, and have maintained it more or less since. When I periodically stop it for a month or so, I get anxiety attacks, migraines, and obviously weight gain. So, I just don't stop it.

taurath2• 25 days ago

As a counter example, I found myself unable to eat anything at all even with anti nausea meds, and my head utterly in a fog that felt like I was becoming ill.

catigula5• 25 days ago

This sounds concerning to me.

vladmk• 25 days ago

Mice are not people, but interesting link

randycupertino3• 25 days ago

I'm on GLP-1 and it's completely stopped my urge to online shop. I used to browse/shop for fun and out of habit or when I was stressed out or wanted a treat etc. Entirely resolved! I've also lost 40lbs on it.

sandcat_• 25 days ago

I'm curious, has it affected pleasure at all in other areas of life? Are things you used to enjoy still as enjoyable? Is it more the "addictiveness" of things that has dropped, as opposed to how enjoyable they are?

(Never tried them myself, but very intrigued by them.)

rubicon332• 25 days ago

Do you honestly believe in the so called “free lunch”? I mean there are MANY substances you can presently take that make you feel way better, but always come with a cost or a downside. Why should we believe GLP-1 class drugs are any different?

meetingthrower• 25 days ago

To the others on this reply, I take 1/4 dose of the "clinical dose" and it has been life changing. I've lost 30 lbs. I've done that in the past, but for me that was harder than ranger school in the army.

I LOVE food. Eating out and family dinner were always important to me. I was very worried that I would lose my pleasure in this.

I haven't.

But now I can just eat 1/2 slice of pie. Or 1 scoop of ice cream, etc etc. I don't have the crazy urge to EAT IT ALL.

Also I loved drinking. I actually still love drinking. But I get done at 2.5 drinks. And once a week.

It adds up. Makes you wonder what free will is.Variance in GLPs are naturally occuring. I find the people who say "I forgot to eat" relatable now. Our bodies were not designed for abundance. At least not mine.

microgpt8• 25 days ago

I wonder if it will reduce usage of HN

jbird99• 25 days ago

Could be related to endorphins and BDNF, similar to the effect from fasting.

y-curious• 25 days ago

I got severely downvoted in the past for badmouthing GLP1s here. Then I did my research, got on them and I take it all back. These things are on par with statins in terms of potential societal impacts.

PeterHolzwarth3• 25 days ago

That's quite admirable to correct yourself in public. Good on ya.

nubg• 25 days ago

Yes. I wonder if taking GLP-1 made him have higher morals as well!

sph• 25 days ago

Very weird (or funny?) to use statins as an example of a ‘good and effective’ drug.

incognito124• 25 days ago

Why do you say that? My first exposure to statins was in https://myticker.com and they seem somewhat important

9x397• 25 days ago

That says more about the harmful effects of obesity than anything.

PeterHolzwarth3• 25 days ago

That's kind of the point.

HedonicEscal8r• 25 days ago

GLP-1s are far more effective than statins.

SubiculumCode10• 25 days ago

GLP1s are one of today's real, true, modern miracles. It deserves a Nobel, but not to one person, but the teams upon teams upon teams that made it possible to get here.

api2• 25 days ago

A central flaw in the Nobel is that it rewards one or two people for what is often the work of teams.

taurath2• 25 days ago

It’s so funny, because they did well for you you’re now incredibly on board for all of society.

I tried them and my health got massively worse and I couldn’t eat at all, on a sub minimum dose.

phil218• 25 days ago

These things are on par with statins in terms of potential societal impacts.

I put them just under antibiotics. In terms of quality of life years given back at a population scale.

hellzbellz123• 25 days ago

As a habitual habit developer, Im keeping my hopes up that in 5 or 10 years, this is something that can help me and many others.

I've read experiences from people on illicit substances that claimed they helped them quit.

It would be beat if this carried over to things like caffeine/nicotine/thc/etc.

buck7464• 25 days ago

There's anecdotal accounts of GLP meds helping with a range of addictions. Of course in science anecdotal accounts are the lowest tier of evidence, that's only top shelf in law.

declan_roberts8• 25 days ago

It's not just anecdotes. Eli Lilly is actively in trials with a glp-1 peptide brenipatide for treatment for certain kinds of addictions, such as alcohol, smoking and opioid addictions.

kube-system9• 25 days ago

I believe it. I never heavily drank but I have very little interest in drinking on tirzepatide. The “it would be nice to have a drink or two” on a Friday evening just vanished.

zhivota3• 25 days ago

Tirzepatide at 1mg/week reduced my muscle soreness. I felt less depressed but this might just have been situational because I've been plagued by bad soreness after working out for years.

Unfortunately after twelve weeks I had to stop because I felt a lot of nausea and tenderness in my upper abdomen, and was worried it might be pancreatitis developing. I'm not sure why it would happen at such a low dose but the symptoms reduced pretty quickly as it wore off.

I may go back on later with a dose spread over a longer period with the hypothesis that the drug has a longer half life in my body and what I experienced was a gradual build up. Considering I lost 15 pounds over 3 months as well, I believe this to be very plausible.

tapoxi3• 25 days ago

I got pancreatitis from Zepbound, but it was indirect.

Turns out rapid weight loss can cause gallstones, especially if you're genetically predisposed to them. I had one that ended up stuck in the bile duct, causing acute pancreatitis. I had to get my gallbladder removed shortly after and hundreds of stones were found.

I would consider getting an ultrasound since the stones don't just go away when you stop taking the drug.

(Gallbladder removal aside I had no lasting issues and kept the weight off.)

zhivota3• 25 days ago

Thanks for sharing, it makes sense. Even before taking Tirzepatide I have had issues my whole life with greasy / fatty stool, and now that I've had reason to research the gall bladder, it does make me wonder if perhaps I also have stones.

perilunar• 25 days ago

Wouldn't that be cholecystitis (and a cholecystectomy), not pancreatitis?

rossdavidh• 25 days ago

Might be worth trying live yogurt in the meantime, per the article?

zhivota3• 25 days ago

Yep one thing I did as part of going off tirzepatide was go immediately on a high fiber and fermented foods diet. It has helped a lot actually.

It's quite hard to maintain over time is all, I have a lot of social occasions where healthy choices are not really available, and from experience I know that over time I'll slowly drift back towards an unhealthy eating pattern. The modern world is just geared that way, unfortunately.

storus• 25 days ago

Metabolic theories of mental illnesses and cancer are seriously understudied.

joshuamcginnis3• 25 days ago

Studies show almost all subjects regained the weight and reversed gains within 2 years. This means underlying issues (e.g., food addiction) aren't being addressed. Short of changing habits, the only maintenance solution is lifelong drug use and that doesn't sit well with me.

crooked-v15• 25 days ago

Plenty of people have lifelong drug use of, say, caffeine, or aspirin as a blood thinner, or various antihistamines. Why is this somehow worse? Particularly keeping in mind that it's very easy to make, so once the patents expire, it's going to be dirt cheap as generics everywhere.

joshuamcginnis3• 25 days ago

I'm just sharing my personal preference and not trying to tell people how to live their lives. I don't like personally like the idea that I'll only be healthy if I take this drug for the rest of my life when I could (again - speaking for me), be more disciplined about the food I put into my body.

wpm5• 25 days ago

Why not? People take depression meds, blood pressure meds, all kinds of meds for their whole life. I'll be on omeprazole for reflux my whole life. It doesn't solve the underlying problem of my gut being prone to overpumping acid into my stomach. So omeprazole is problematic?

The underlying issue is being treated, it's treated by taking the drug. It works. It's doing its job.

I'd be curious as to how you came to this conclusion.

joshuamcginnis3• 25 days ago

I think there's a distinct difference between taking medicine for things you can fix on your own (diet + exercise) vs things you cannot (excess acid production).

9x397• 25 days ago

If they were a normal weight they would not have been prescribed the drug. The underlying issue is they're overweight because they eat too much. Anything more is speculation.

There is usually no free lunch when it comes to pharma, and extrapolating long term or lifetime dependence as being equivalent to short term interventions is an unsupported leap.

hamhock6662• 25 days ago

If you can find a way to use your own free will and self-discipline to stop the bad condition then that seems preferable to using a drug. Maybe someone doesn't have the willpower in which case it's good that we have the drug.

With regards to omeprazole, I changed my diet a bit and no longer needed the omeprazole. I don't know exactly what it was, but if you can get off of a drug because you don't need it anymore that seems ideal.

htk• 25 days ago

No, the symptom is being treated, not the underlying issue. And that's ok, but treating the underlying issue, when possible, is better, as the problem ceases to exist.

soared• 25 days ago

Omeprazole is not great long term FYI - worth talking to your doctor or getting a second opinion to discuss.

ElProlactin2• 25 days ago

People take depression meds, blood pressure meds, all kinds of meds for their whole life.

And a lot of these medications have side effects that can affect quality of life negatively in other ways. That doesn't mean they're not helpful, or shouldn't be taken. But the "no free lunch" rule usually applies, sometimes to a noticeable degree.

Netcob3• 25 days ago

Because usually you can't study long-term effects before releasing a drug, and even then it can take a long time for them to surface.

I took antihistamines basically throughout my 20s. My allergy specialist said there's no reason not to. I developed some other issues and wanted to stop taking antihistamines to see if that would help (or get a hint whether they were causing it) - but that got me into itching hell for weeks.

In some online forums people reported the same and shared ways to get out of that "addiction" without going insane from itching.

My doctor didn't want to believe it and there was no research on it. That only appeared a few years later in the form of a paper called "Unbearable Pruritus After Withdrawal of (Levo)cetirizine" (2016). In the US, the FDA issued a warning in 2025, which is also the time when I heard about it. None of the doctors I went to back then reported this to anyone, so I'm surprised it got discovered at all.

As for my other issues I have no way of knowing whether they had anything to do with long-term antihistamine use. I'm a sample size of one, and none of the other stuff is quite as clear-cut as "unbearable itching".

I've had other issues with prescription drugs that didn't make the official list of side-effects and sometimes those side-effects don't just go away once I stop taking the drug.

That's why I'm very cautious when trying drugs I never had before, and even more so when it comes to taking them long-term.

herbst5• 25 days ago

I know several people who stopped both of your examples and only used them for a while until the underlaying issues got fixed. I am just in the progress of stopping with anti depression meds. Without bigger issues.

Maybe in America you do, here in Europe I am not so sure about that

jbaber• 24 days ago

First, I agree with your comment.

But since you specifically bring up omeprazole: I backed off of pantoprazole by getting a prescription for half-dose pills (since they're time released, you can't just cut them in half), then decreasing frequency (alternating days, then tapering off) and retained the benefits.

There are plenty of confounding factors in my case, but checking occasionally if you can back out of a drug is worthwhile.

spicyusername• 24 days ago

Because it's pretty likely some of these have negative long term effects. And some of those long-term effects are probably pretty serious.

Many people taking these kind of drugs are gambling with their well being. No doubt that in many cases that gamble is worth it.

But issues that can be solved with non-pharmaceutical solutions, such as with weight loss and lifestyle changes, are really better solved that way if possible. There's no risk of longterm effects and it helps foster a larger culture of healthy living in society generally, reducing the lilihood of the problem in the general population.

butlike4• 23 days ago

But isn't the point to not have to be tethered to a medication forever?

anon291• 25 days ago

Why? If you have too much help or whatever being produced such that your body eats too much, just take a drug. The harm of being fat is worse than anything ozempic does

PeterHolzwarth3• 25 days ago

A couple years of reduced weight, and all the benefits that entails, doesn't sound bad.

vidarh3• 25 days ago

Given that we know that diets and changing habits doesn't have lasting effects, what doesn't sit well with me is to risk my health to avoid taking a drug that helps.

brazukadev2• 25 days ago

changing habits do have lasting effects, I'm not part of this "we" that doesn't know that.

gedy• 25 days ago

The "underlying issues" are not all moral failings as you hint. In my case, as I've aged my appetite due blood sugar/insulin resistance/etc means I'm basically hungry all the time if I restrict calories to maintain lower body weight. Yes - even if I exercise frequently. Yes - even with healthy food and snacks. My wife tells me my stomach is growling at night.

I will slowly gain about 10-15lbs a year due to excess calories if I try to maintain weight at < overweight BMI. GLP-1 drugs have been great to take that edge off.

LaurensBER• 25 days ago

I've gained and lost 10kg twice in my life. Maintaining the weight loss isn't that hard once you've a rhythm dialed in.

In my case I just weight myself daily, track the weight and scale my food consumption with the current trend. If I'm gaining weight I'll skip a meal.

It takes a while to figure out what works for you but I can tell you that making small lifestyle changes to maintain your weight is fairly easy compared to figuring out how to lose 10 kg.

kolinko6• 25 days ago

Just because it wasn’t hard for you doesn’t mean it isn’t hard for the others. Grom what you said it seems you just had some bad habits you had to fix and that’s it.

coffeemug• 25 days ago

When I was lifting weights I went from 170lbs to 210, and back to 170. Doing that isn’t technically hard, and maintaining is even easier. But I had to think about it _all_ the time. Maybe it’s because I’m older now, but I just don’t want to spend that much effort thinking about food.

3stacks• 25 days ago

It’s the food equivalent of declaring bankruptcy. If you don’t fix the behaviours you’ll just end up in debt again.

kolinko6• 25 days ago

This assumes underlying behaviours are core reason. Research (tein, adoption) suggests otherwise

flextheruler• 25 days ago

Unfortunately for a lot of people with weight issues it stems from becoming overweight during puberty which is uniquely bad. Your body's appetite signals are permanently impaired if you become overweight during puberty because during this window your fat cells don't just increase in size, but also in number and this increased quantity does not go away once created. Fat cell shrink as weight is loss, but they are not destroyed and they are responsible for appetite signaling. It's one of the reasons that childhood obesity is actually leagues worse than it first appears and I think should be considered child abuse in extreme circumstances.

apt-apt-apt-apt• 25 days ago

What you said isn't unique to puberty, it's the same with being overweight in adulthood (AIUI).

SubiculumCode10• 25 days ago

And this morning, I cut another hole in my belt. Turns out, losing weight and being thin was never about willpower or laziness in the face of absolute food abundance. It was mostly about whether a person was born lucky enough to have a moderate appetite, or was born burdened by exaggerated appetite.

The underlying issue is physiological food cravings, not some personal failing or lack of willpower, and GLP-1 absolutely addresses those "underlying issues". That it isn't some one and done pill is hardly a realistic expectation as that would require probably genetic and epigenetic reprogramming.

nihonde• 25 days ago

The idea that appetites are assigned at birth is a bold claim. Is there evidence to support it?

fragmede4• 25 days ago

The drug stops working if you stop taking it? Shocking! Heart medication for hypertension also stops working if you don't take it. Sure there's a vast conspiracy by the pharmaceutical industry to hook us all on drugs because we can't learn to exercise, but that's hardly Ozempic's fault. Now if you were looking at brain surgery that zaps the reward center of the brain causing permanent changes so the patient was less addicted to food, but the patient kept needing to have brain surgery, then you'd have a point, but "drug stops working if you don't take it" is hardly the gotcha some make it out to be. Insulin also stops working for diabetics if they don't take it. That's kind of medication's whole deal.

Now that we know obesity can be controlled via medication, and it'll cost $foo over the lifetime of the patient, the next step is to optimize. If there is a treatment involving ultrasonic brain surgery that costs less than $foo, the expectation is for the market to find that. Ultrasonic brain surgery is in its infancy, but it's already showing utility for Alzheimer's and addiction. The real question is if the pharma companies are going to be able to keep it from going mainstream because it's less profitable for them.

JumpCrisscross8• 25 days ago

almost all subjects regained the weight and reversed gains within 2 years

Source? I thought it was 2/3rds of the weight regained, which is still a substantial long-term loss.

shlant3• 25 days ago

supposedly that comes mostly from observational studies whereas RCT's seem to show that at some point full regain will probably happen (although can take 1-2 years). The Observational studies don't seem to control for people stopping GLP-1's but still trying other drugs/weight loss methods which is where the discrepancy from RCT's seems to be.

SOLAR_FIELDS• 25 days ago

Statins are a well understood mechanism of action for controlling cholesterol. We generally understand that people with cholesterol problems leverage statin therapy to address those, and there is a well audited corpus of placebo controlled double blind trials that demonstrate the efficacy of the solution for statin therapy. If you discontinue the statins, you lose the benefit to some extent. How is this situation fundamentally different?

tqi2• 24 days ago

Agree, same can be said of exercise.

I think people consciously or unconsciously consider being overweight a moral failing and so are quick to point out the flaws.

mukbangpervert• 25 days ago

What facts do you have that make you certain that the underlying issue is "food addiction" rather than, say, a difference in body chemistry that changes perceived hunger levels?

PaulHoule3• 25 days ago

It's not like anything else in terms of drugs, surgery, or lifestyle changes has been proven safe and effective. A person who is dependent on opiates or caffeine or cannabis can possibly live without those substances, you can't go "cold turkey" from food.

Funny I just shot myself with a Zepbound autoinjector for the first time! My primary care doc told me he thought I was a good candidate a year ago but that he had trouble getting insurance to pay for it, it took me a year to get in with a specialist, insurance approved it right away, and now I am supposed to keep a food an exercise log.

I am well in the obese BMI range but I've been active my whole life (e.g. I can't see how people can get through the day without going to the gym or something) so I have a high lean mass and don't look that fat with my clothes on. I've struggled for years with various conditions associated with "metabolic syndrome" and I'm on numerous maintenance medications already and may be able to delete some of them.

I am currently around 250 lbs which has been my usual for the past 20 years or so. Had some luck with Zone, ketogentic and bean plan diets but couldn't stay on any of them indefinitely. Got my weight down to about 208 lb in six months when I quit taking antidepressants at my doctor's suggestion (never went back), had something like a manic episode where I manifested an "evil twin" who was vain highly motivated [1] and worked out like... a maniac and I also discovered I had TMJ dysfunction and took load off my jaw by throwing comically random food (cashews, seaweed, celery, potatoes, carrots, pork, ...) into a pot and grinding it with an immersion blended. Not sustainable, not least because my evil twin's antics got me kicked out of the gym.

[1] as-a-fox one axiom is that "I never push on a string" and have a hierarchy of goals, non-goal goals and non-goals; my non-goal goals are his OKRs

dmayle3• 25 days ago

The issue isn't food addiction, it's a broken hunger response (broken by Howard Moskowitz intentionally in the name of profits)...

You have to change your food regimen completely (higher fiber, more protein, less sugar, less carbs, less fat), and that's tough to do when you're surrounded by options that aren't...

I think the real problem is that the symptom we're trying to treat is "overweight", and it's actually a two-stage problem... Fix the hunger response... and only then work on fixing the weight... Fixinig the latter without fixing the former means you'll always gain the weight back, fixing the former doesn't guarantee you lose weight (and is only temporary, if you're using drugs for it)... You have to go after both problems.

basch• 25 days ago

We shouldn’t ignore grocery stores and marketing.

Aisles and aisles of sugar drinks and colorful sugar packaging.

The way society leaves it up to people to make their own decisions creates the problem at scale.

Society essentially has to take weekly injections to avoid the temptation of coca cola.

mynameisash2• 25 days ago

What breaks the hunger response, and how does one fix it?

Maybe it's well-known, but I read the starvation response Wikipedia page[0] and didn't grok it.

[0] https://en.wikipedia.org/wiki/Starvation_response

rfv6723• 25 days ago

The only underlying issue is an evolutionary mismatch: human evolution is too slow to keep pace with the modern abundance of food.

What we now call food addiction is exactly what kept our ancestors alive during famines.

epihelix• 25 days ago

If your biology is working against you, why not fix your biology?

I'm not someone who needs to take GLP-1 receptor agonists, but if I had any issues with weight then I'd have no issue taking them life-long. The long-term health benefits are already strong enough to make it a no-brainer. If you are overweight and a GLP-1 drug helps you lose that weight, you will very likely live a longer, healthier and happier life by taking the drug.

All that said -- this article was discussing a new paper in Cell Host & Microbe (high-impact Cell Press stable journal), https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(2... . And the point of that paper is that, at least in mice, the anti-depressive effect of GLP-1 receptor agonists was related to a change in gut microbiota, and not to activation of the GPL-1 receptor. It's work in mice only, so whether or not this holds in humans is unclear, but the researchers showed this worked in mice lacking the GLP-1 receptor and via fecal microbiota transplantation of bacteria from the guts of mice taking GLP-1s.

So, if all you cared about were the mental health benefits of taking GLP-1s, then potentially you could gain these by simply changing your gut flora, without taking a GLP-1 drug at all. That might sit much better with you, by the sounds of it.

port11• 24 days ago

If the food abundantly available is full of unhealthy ingredients and nutrient combinations meant to make you addicted, why not fix that?

We blame biology and people’s willpower a lot, instead of considering how plenty of other or previous societies don’t/didn’t have this issue.

mullingitover• 25 days ago

Diet programs as a weight loss strategy are utter failures, and it’s malpractice to push them as a treatment. Yet there are still people pushing them as something that’s perfect, if only you didn’t screw them up.

When a treatment can’t fail and can only be failed, it’s big red flag for me.

thaw135793• 25 days ago

The issue is that our modern world has engineered our food to be highly energy-dense and incredibly appealing, so the root cause is an evolutionary mismatch with our environment, which has diverged incredibly from early humans.

Personally, I look at GLP-1 agonists as akin to wearing glasses. Some people are just born without the ability to regulate their appetite in accordance with our society, but there is a tool / prosthetic to change that, often that's a lifelong solution.

sakopov• 25 days ago

Does loss of muscle mass, commonly associated with Ozempic weight loss, become an issue after regaining the weight? Can it result in proportionally more fat at the same body weight as before if exercise wasn't part of the regiment?

theshrike795• 25 days ago

_All_ weight loss results in loss of muscle mass unless you do something about it.

If you ingest less calories, you lose both muscle and fat mass.

amanaplanacanal7• 24 days ago

I believe loss of muscle mass is commonly associated with other weight loss methods too. It's not just ozempic. You need protein and exercise no matter how you are losing weight.

teliosix4• 25 days ago

Totally agree. My father is 75 and started taking GLP1. He stopped drinking immediately, lost 25lbs already and I can't imagine hasn't already added some time to his life.

The calculus at 75 is much different than at 35 in terms of what "for life" means.

It seems like there could be an issue too that it just stops working that well 10 years down the road. Not an issue for my father at 85 the way it would be for someone at 45.

whazor• 25 days ago

What were the numbers again? Because I remember a significant amount of people actually did not regain weight. Although the majority did.

amunozo• 25 days ago

But it does sit well with pharma companies.

theshrike795• 25 days ago

Blood pressure and high cholesterol can both be genetic. So people just are on meds for both all their life. It doesn't cure anything - it's not supposed to.

QuantumGood• 24 days ago

The "here's where you're getting it wrong" discussions on glucagon‑like peptide‑1 receptor agonists are paralleling AI discussons. Interesting to watch these two domains of knowledge sparking (mis)framing arguments happening at roughly the same time.

crooked-v15• 25 days ago

I'm curious if this post will also have the same phenomena I've seen before of people springing out of the woodwork to post moralizing comments about people shouldn't rely on drugs, about how actually GLP-1s are bad because they don't fix problems indefinitely with a single dose, about how people should fix their problems by just having more willpower, talking about 'but what about the unknown side effects?' of drugs that have been in use for twenty years already, etc.

nonethewiser• 25 days ago

Why shouldnt it?

buck7464• 25 days ago

Semaglutide has been used for diabetics for roughly 20 years. The FUD angle is just people rambling against something that doesn't affect them personally. Everyone knows the only things that matter are what effects "you", everything else is just fantasy. If we could rid ourselves of that mindset we could build a much better world.

SubiculumCode10• 25 days ago

And it surely did. Like clockwork. And it is annoying.

sp527• 25 days ago

A lot of people have had to accept that they've wasted a considerable amount of time and energy on something that is being heavily devalued by GLP-1's. They've also lost an important vector for status signaling. This particularly offends narcissists and the hyper-competitive.

They desperately need to restore status, and one easy option is, in effect, "oh you're still ugly on the inside."

By way of analogy, it has the same underlying motivation as the various sumptuary laws that arose in response to the mass-manufacture of silk.

The Elizabethan Restrictions: In 1574, Queen Elizabeth I passed strict sumptuary laws to curb "unprecedented social mobility". The Crown decreed that no woman could wear silk cloaks unless her husband was at least a knight, and restricted fabrics mixed with gold or silver to Earls and above.
Income Thresholds: In 14th-century England, if an esquire or merchant wanted to wear silk, they had to legally prove they made at least £100 a year. If they didn't meet the financial threshold, wearing the fabric was a criminal offense.

metalman• 25 days ago

so, the whole mouse thing is a scam, and now they are openly testing on us, first, and publishing in psychology today to see if we notice.fiendish.

microgpt8• 24 days ago

all of life is an experiment. If you're religious, you might consider evolution as a god. If not, just know there are so many random variables that everyone is a unique experiment with sample size of 1.

OptionOfT• 25 days ago

My insurance stopped covering, now I'm looking at $450 for Zepbound / month. Just the weight coming back is making me more depressed...

jzkdroid2• 25 days ago

You can probably use some coupons like goodrx to get it for $300 a month.

cjbgkagh6• 25 days ago

I get mine on the black market, 50c/mg for semaglutide, $3 per month at my current rate of usage. I’ve been on it for years, I was getting gray market at $12/mg for 3 years before RFK clamped down on that market. It’s exactly the same stuff (for me, no guarantee for others), had it tested in a lab and as the side effect profile is on point. It massively relieved my ME/CFS, back when I started there was no way I could have gotten a prescription let alone insurance to cover it.

declan_roberts8• 25 days ago

GRAY market is way undercounted in peptide use. Go to the gym and there's like 25% of the people there taking gray market peptides (some for weight, some for injury repair, etc)

faangguyindia37• 25 days ago

Without long term positive dietary changes most people are unlikely to keep the weight off unless you want to take this stuff for life.

declan_roberts8• 25 days ago

I have to exercise and go to the gym for life already?

declan_roberts8• 25 days ago

Gray market peptides are excellent. You can do you own independent lab testing, buy with a group who's testing, or buy from a reputable vendor who pre-tests before sales.

Even after all that it comes down to like $50 a month at the highest dose.

relaxing• 25 days ago

Where do you even start finding sources for all this?

whatthesmack• 25 days ago

I had the same issue with Zepbound (tirzepatide) 10mg/0.5ml when they wanted to push me to Wegovy (semaglutide), even though Zepbound was already working and helping. Zepbound isn't even on their formulary now.

I wrote the insurance company a detailed letter (helped by AI) containing evidence for the benefits of Zepbound over Wegovy and Zepbound over nothing, as well as documented the benefits I already experienced taking the medication. They approved coverage based on this pushback, and I just paid $25 for 3 months' supply.

Might be a potential avenue for some folks...

gavinray2• 24 days ago

Posted prices of Chinese gray market bulk peptides on Twitter recently

It's $95 for 10 vials of 30mg Tirzepatide, which at the highest dose of 15mg/wk, is still 20 weeks for less than $100...

https://x.com/GavinRayDev/status/2067348581418434564/photo/1

Finnrick will even test your peptides if you agree to them publicizing the results and the vendor:

https://www.finnrick.com/products/tirzepatide

replwoacause4• 25 days ago

Hasn't done jack shit for my depression.

Also worth mentioning GLP1's are known to cause anhedonia. So there's that...

jfaat• 25 days ago

Known to who? I just did a quick search didn't see anything that like a scientist or physician said about this. Someone who describes himself as a 'biohacking educator' said it without citing sources though.

declan_roberts8• 25 days ago

I can say the things I like, I like the same or even more (higher sex drive is one noted example). I can sit and program for hours now without thinking about other things. I assume this is what people who took Ritalin felt.

I do notice it makes it harder for me to get up and do certain harder, outdoor chores.

downrightmike• 25 days ago

Yup, helps Gila monsters go so long without eating/doing anything

devcatapult• 25 days ago

What about the reports of bone density loss? Any downsides to this?

kolinko6• 25 days ago

What reports?

pitaj• 25 days ago

From what I've seen it's mostly related to just losing weight in general (less weight -> less musculoskeletal stress -> weaker bones and muscles). Weightlifting can counteract it.

phil218• 25 days ago

Like all weight loss, you will lose lean muscle mass and bone density as part of it if you do not take corrective measures. And even with such measures, you will likely lose some either way for the medium term. It's very difficult to lose only fat during a long term calorie deficit.

The answer is getting into a regular schedule with resistance weight training. Obviously not all that many people will pull it off, but if you can pull it off you can stave off the worst of the side effects in many cases.

swalsh• 24 days ago

I have a composition scale, and regularly get vitamin d, and calcium tests (had issues with both) since taking the wegovy pill in Feb, I have not loss any bone density, and pretty minimal amount of lean muscle (i think any weight loss will have some lean mass loss). I have lost fat, kicked drinking, and my lipids improved dramatically.

dyauspitr2• 25 days ago

What’s the downside to this magical drug. There has to be a downside…

ceejayoz8• 25 days ago

Why does there have to be a downside?

What was the downside of washing hands before surgery?

9x397• 25 days ago

Because our bodies are delicate systems of networks, and inputs in one area can have complex/unpredictable outputs elsewhere, it seems.

Typically, if something "works", there often appear to be side effects. A free lunch is rare.

https://www.uclahealth.org/news/article/understanding-medica...

OscarCunningham• 25 days ago

One argument would be that Ozempic doesn't give your body any additional resources. It just triggers your body to behave in a different way. But if the changes it causes are universally good, why didn't evolution already make your body work that way?

I suppose the counterargument would be that modern life is different from the evolutionary environment, and so it's possible for a change to be beneficial now that wasn't beneficial then. But it would still be good to understand better the mechanism of the effect of Ozempic on things like addiction.

kolinko6• 25 days ago

And downsides of penicilin? There are some but they are massively offset by not having alt consequences

subtlejellyfish2• 25 days ago

Penicillin resistant bacteria?

culi• 25 days ago

There are massive downsides to any antibiotic. A single dose of a broad-spectrum antibiotic can permanently alter a kid's gut microbiome and make them more likely to develop a variety of mental health issues like depression

https://theconversation.com/how-childhood-infections-requiri...

https://www.scientificamerican.com/article/a-single-course-o...

sevenseacat2• 25 days ago

As someone with a severe allergy, lots of downsides to me!

Aaargh203184• 25 days ago

The downside is that they make you eat less thereby taking away one of the few things that make life worth living.

SubiculumCode10• 25 days ago

That is the silliest take ever. I am on GLP-1s, and I still enjoy my food..maybe more than ever before.

microgpt8• 24 days ago

You should get in touch with a therapist to help you find meaning in life that isn't just eating food. Or get a girlfriend - i heard that helps most people.

cflewis4• 25 days ago

Nothing in this world is free, GLP-1s have their downsides (excluding cost).

Mostly it's nausea and gastrointestinal distress side effects. These tend to cool down over time, but it'll put a ceiling on how big a dose you can tolerate. Some people can't tolerate a dose at any level.

pandaman4• 25 days ago

Even if there are zero effects other than the advertised weight reduction, one downside is obvious from the comments here - some people will stop exercising.

While exercise has many positive effects, which I'd argue are more important than the weight loss, the latter is the primary reason many people exercise and likely to stop when given the weight loss by other means.

subtlejellyfish2• 25 days ago

We should stop telling people that exercise is a primary driver of weight loss.

That said, exercise has a direct impact on metabolic health which is pretty necessary to maintain a healthy weight.

chrisco2552• 25 days ago

Most people are achieving weight loss by dietary changes. It takes a massive amount of exercise to significantly alter your calorie balance. Definitely good for you either way but most people who exercise also want to be toned or muscular.

phil218• 25 days ago

one downside is obvious from the comments here - some people will stop exercising.

Is there any source on this? The precise opposite has happened in my experience. I was an early evangelist for these drugs, and have many dozens of people who I talk to regularly who have since taken them over the years. I cannot think of a single person who went from regular exercise to reducing or eliminating it after taking the drug. Exactly zero.

I can think of well over a dozen folks who started regular exercise for the first time in their lives after losing 50 or more pounds.

Certainly many who did not change their habits either way. But overall this matches with what the trainers in my gym report. They were initially worried GLP-1s would reduce their client base, but the exact opposite has happened for them. It's brought an entirely new demographic into play and business is booming.

which I'd argue are more important than the weight loss,

You would be making an argument contrary to most established science on the topic. Exercise is important and quite beneficial to health. Obesity is far worse. Not many obese people working out regularly to start with though, so I don't think this point holds much water to begin with. We are not a nation full of obese gym rats.

tayo42• 25 days ago

Don't they age your face pretty badly?

sevenseacat2• 25 days ago

Not by themselves - its the result of weight loss that can make your skin sag a bit.

declan_roberts8• 25 days ago

Some downsides:

1. They make you stop eating, which for most of human history kills you.

2. They are a life-long treatment and kind of expensive unless you go gray market.

3. Gastrointestinal issues especially when titrating up.

chrisco2552• 25 days ago

1. They don't make you stop altogether, they just make you feel full on less calories, which is good when you are in a calorie dense environment like modern society.

2. Not necessary here either if dietary habits are permanently altered, which can happen more easily after several months on GLPs.

3. Perhaps!

weregiraffe3• 25 days ago

What's the downside to antibiotics?

dyauspitr2• 24 days ago

Gut biome destruction that has some far reaching effects including mental ones.

cagenut• 24 days ago

the downside is it allows us to continue to avoid solving the real problem

ideologues will tell you this is that all mankind suddenly lost their ability to exert self-discipline a few decades ago

science points to a broad combination of things like corn syrup and seed oils simply making food too addictivly-rewarding and calorie rich for our nervous and endocrine systems to handle.

so, do we reform the farm bill and fast food industries, or do we take the antidote?

microgpt8• 24 days ago

No one is steering the ship. You have the same right to try to fuck over Pepsi (which owns like half of all addictive food brands) by taking GLP1RAs as they do to try to fuck you over by putting who knows what in their food.

Some of that stuff they put in food is probably designed to antagonize your GLP-1 receptors, you know. They didn't know what those were, but they did know when they put it in food, you bought more! *cough* Pringles

mathgladiator• 23 days ago

Solving the underlying problem has been amazing. I wish more people could do it.

I have given up helping others since my solution was to embrace a carnivore lifestyle. But then im just in a tribal cult with amazing health.

danny_codes• 24 days ago

Long-term downsides tend not to show up in studies for many years. For example, these drugs might increase cancer rates, but we wouldn't know for a few decades.

I imagine though that on-balance they'll be net positive because being overweight is just so bad for you.

TMWNN• 25 days ago

The more I hear about GLP-1 drugs, the more I think there is something to the joking suggestion of putting it in the water supply.

crooked-v15• 25 days ago

I personally think that once the patents expire, it will be about as universal as antihistamines, or if not, only because of the larger side effects like rapid weight loss causing gallstones.

qsxfthnkp23222• 24 days ago

Thank god I have RO at home with people suggesting things like this.

Positive or negative, I don't want drugs in my water.

jona-f2• 25 days ago

The "gut-brain axis" is mostly bullshit invented to cope with the fact that doctors have sent patients to shrinks for decades with real sicknesses. Everybody knows you feel bad when your digestive is out of balance. It's the same english word for "I'm sick" and "I feel sick" since forever. No magical newly found "gut-brain axis" needed.

Eating junk food, especially sweetened food is a drug. You can do a withdrawal and get the reduction of food noise reported with semaglutide without getting dependent on another drug with so far unknown long-term effects.

theshrike795• 24 days ago

But the drug feeds the flora in your gut, which tells your brain to crave more of it.

Like if you completely cut off sugary foods for 2-4 weeks you won't crave them as much. Why? The gut flora that feeds off sugar specifically dies off and can't send as strong signals to your brain.

Thus: gut-brain axis. It's a thing and will become more important when we study it more. Your brain isn't as much in control as you think.

jona-f2• 24 days ago

Your explanation doesn't seem plausible to me. If your stomach and small intestine is working properly, the bulk of the bacteria shouldn't see much sugar. Afaik the mechanisms how the intestines regulate the gut flora are not well understood. At least not to the point where there are any working treatment for the many widespread digestive problems. There is some slow progress around fecal transplant research.

blubber• 25 days ago

In mice

Edit: the title should have such a tag

Illotus3• 25 days ago

Great drugs. Have dropped 10+kg couple of times and tried a few more with low carb. Dropped 20+kg with Ozempic and it boosted me to exercise. Its wonderful that even a string of bad nights don't push me to overeat: even if I eat more during the day it tapers of in the evening whereas before ut would just continue.

tsoukase• 25 days ago

From my real world experience of a few dozen patients, there is definitely a mood boost but only to those who lost weight. The effect may be due to the weight loss confidence and/or other mechanism. The cause seems difficulty to find.

My advice: in monopolar depression with increased weight especially due to binge eating take the SSRI Fluoxetine 20mg 1 up to 2 daily. It will make wonders.

sleight42• 25 days ago

Wish I had that microbe. Ozempic made me suicidal. Still here though. Zepbound doesn't that that effect. Maybe the smaller dosage of the GLP-1.

microgpt8• 24 days ago

It just says 403 Forbidden?

butlike4• 23 days ago

There's no free lunch so what's the downside? I don't believe in ghosts, and I DON'T believe in miracle cures.

What Ozempic does to the gut-brain axis

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