What Ozempic does to the gut-brain axis
psychologytoday.com
psychologytoday.com
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.
Is the Modafinil used for alertness or a different off label purpose? I'm always interested in potential helpful interventions.
I use Modafinil and Amitryptiline as a rather unorthodox method for treating dysautonomia which seems to be an intrinsic precursor to ME/CFS, at least in my case where I have hEDS from a number of TNXB variants.
My overall theory is that a combination of anxiety disorders (genetic inability to ameliorate stress) pushes me into a Sympathetic state and keeps me there to the point that cytokines (or some undiscovered small molecule) are created by the immune system to knock me out of that state as a backup to other mechanisms that have stopped working. So I studied some psychopharmacology to design a drug combo that wouldn’t override the autonomic state so I could both work with my natural rhythms (using weaker ligands) and increase the magnitude of the swings so that I could spend enough time in the Parasympathetic state to obviate the need for the immune system backup. I take a lower dose of Modafinil (100mg started and stayed at this dose no apparent tolerance build) and am genetically very sensitive to caffeine so that and one coffee is enough to get me amped for the entire day, but I need amitryptiline to bring me back down to sleep (started as 25mg and many years later I’m at 125mg due to increasing tolerance). I do want to bring down my reliance on amitryptiline but I’m working crazy hours and figure I can wait to titrate down my dose later. I’ve been at this same dose for a year now so it’s at least not getting any worse).
Thanks for the information, it's such a frustrating condition with a dearth of good information and research.
Now if you search "reddit eds glp-1" or tirzepatide you'll see tons and tons of long threads of people all saying the same thing - it's the only thing that actually helps.
For me it was something of a miracle, I have two overlapping immune issues and it seems to just turn me into a much more normal, functional person. Including fixing my sleep.
Never was overweight beyond maybe ~15lbs btw when I started or took it, and the effects are 100% not because of just fasting or weight loss. I had tried keto and OMAD before, and been at healthy weight my whole life.
There's a definite auto-immune modulating mechanism and it's so strong it seems better than basically most first-class drugs. Even things like prednisone which are like nuclear weapons don't give me relief like Tirzepatide does.
Btw highly recommend Tirzepatide of the three GLP-1 drugs, for me at least it's by far the most effective and least side effects.
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.
> Nonetheless, average daily energy expenditure of traditional Hadza foragers was no different than that of Westerners after controlling for body size. The metabolic cost of walking (kcal kg−1 m−1) and resting (kcal kg−1 s−1) were also similar among Hadza and Western groups. The similarity in metabolic rates across a broad range of cultures challenges current models of obesity suggesting that Western lifestyles lead to decreased energy expenditure.
> So where does the energy burn in a sedentary population come from vs highly active Hadza tribe members?
P.S.: One theory I've seen is that the extra sedentary-spend is in the immune-system, which may have both beneficial and harmful effects, depending on whether it's doing useful work versus causing problems.
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.
I've heard it widely described as reducing mental noise around food.
Eating healthy food alone isn't solution, you need to make your life active as well.
https://www.verywellhealth.com/glycemic-index-vs-load-521436...
Blood sugars spikes then drops can have different impacts on food appetite.
Moreover, you dont need to eat anywhere close to 5k to be morbidly obese.
1 cup of roast nuts over TDEE will gain you 100lbs in a couple short years
TDEE rises as body weight rises (heavier body burns more)
Overfeeding increases NEAT in some people (more fidgeting, movement)
In some video a woman was eating 8-10 Oranges a day just as a snack on the side.
No knowledge about sugar or calroies, just the thought "but its a fruit its health". No fruits are not healthy
Yes. Fruits are healthy. One orange is healthy. 10 oranges are unhealthy. Same concept applies to water. Drinking too much can be unhealthy as well, but that doesn't change the fact that water is good.
You made that up tho.
10 oranges have a total of roughly 700 calories and 120 grams of sugar while only having 30 grams of fiber. It's mainly sugar. Eating 10 oranges per day crowds out protein, fat and other nutrients.
It's not a made up claim. You are a made up claim, troll.
I know it ends up as pedantry, but specifying the period with every post/restatement is so critical in these threads. 10 oranges a day is unhealthy, but so is 10 oranges a year to someone trying to make a counter point.
Its an issue if you drink orange juice not when you eat it. Eating takes longer and is getting balanced from the fiber.
A diet can be healthy if it's the nutrient combination of different foods that result in certain number of calories, protein, fat, carbs, minerals and vitamins per unit of time.
Healthy in a way, but surprisingly a lot of sugar ( either added or from the fruits)
https://publications.aap.org/pediatrics/article/139/6/e20170...
>Pediatricians should support policies that seek to reduce the consumption of fruit juice and promote the consumption of whole fruit by toddlers and young children already exposed to juices.
It's a lot harder, as many of the comments mentioned, because of caloric density and lack of appetite hacks (sugar, salt).
A can of Mountain Dew is 170 kcal + 46g of sugar.
A navel orange is ~75 kcal + 13g of sugar + 3.2g of fiber + 1.25g of protein.
So take someone from Appalachia with a 4 can / day habit (modest), and that's ~10-12 oranges. That's a lot of oranges to not get sick of eating.
Which is where I think the sugar + salt difference comes in.
It's far easier to overload on the same food when it's stuffed with these appetite attractants than a caloric equivalent of healthy food, because the health food will taste more similar (read: like itself), which will eventually get boring.
if you one broccoli head with one pound of icecream then sure, you will feel hungry again quite soon
If you have a stomach and appetite that are capable of consuming the 15 to 20 lb you need to eat 3,500 to 4,000 calories of similar foods, you ought to call a research lab
1) you didnt eat the most calorie dense foods
2) you dont need crazy calories to get fat, just above your burn rate.
What part are you confused about?
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.
Addiction-like behaviors related to food transcend not only human culture but also even other species.
Do you know what nutrients are? Deficiencies are the cause of the noise. This is an evolutionary feature, not a bug. Your body is expecting you to keep eating alternatives until you eventually stumble onto the foods that make you feel better and then keep eating those. In severe cases you might need more patience with the right foods, but if you already feel like crap and you know you just started barely eating healthier, why stop now?
This search process has been somewhat disrupted by our modern environment, but it's not like the good food isn't right there. On the other hand, you don't need trial and error anymore. There's plenty of information available. You can even go see a doctor and get a blood test to confirm both your deficiencies and everything else I just said.
Does that answer your question?
EDIT: to reply to replies below and I am "posting too fast"...
TLDR: Y'all need to see a doctor.
I used to weigh 400 lbs, had a bad enough drinking problem to cause numbness in my legs (B12 deficiency to boot), and a sky high A1C. I recovered 100% after a decade of this self abuse. Doctor didn't bat an eye back then nor when I recovered a couple of years later. They see it all the time and my "success" story is very common. Most of us understandably find this all too embarrassing to shout about online. We'd get drowned out by influencers trying to sell you crap anyway.
Also, sorry not trying to be callous, but long term deficiencies can cause permanent damage. If you're still experiencing "food noise" after a serious attempt at a planned diet (and magically never had any other symptoms warning you of the impending damage) I have some doubts, but that's a whole different topic.
Anecdotally: no, it doesn't. Maybe it did for you. I spent most of a year once on a predesigned meal plan, and the only thing it changed about the low-key but constant food noise was better knowing when I had a safe margin to indulge a little bit.
I just eat too much of it, because food tastes good and it's a source of dopamine for me. Like most people with food noise.
Also when I get up and finish eating, within 30 minutes my brain is thinking what's going to be the next meal I eat. Food noise.
Yes, some people can lose massive amounts of weight by "just eting right", my brother in law lost 20kg by just not drinking beer anymore. I haven't had a beer in 3 years and didn't lose a single kg. Food noise.
Agreed, and often the root cause is something else in a person’s life (stress, feelings of losing control etc ).
Adding new labels related to food doesn’t do anything to fix the underlying conditions and if anything distracts from them and points the blame at food and physiology, which is not often the root cause of over or under eating.
the perpetrators are the people selling poison under false auspices.
we're not blaming people with pica for eating drywall.
We're blaming profiteers for shoveling garbage into the mouth of anyone with a buck while systematically lobbying to maximize garbage advertising and minimize actual food where feasible and simultaneously incentivizing sales groups as much as is profitable -- all the while trying to convince medical professionals and scientists to produce overtly narrow results to support the public consumption through bogus 'science' papers.
Go into any western supermarket and there are massive aisles of fruit and veg, along with various types of protein.
None of these eating disorders are new. If anything it is far easier to be healthy now.
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.
"Food noise" is much more than just craving calories, we have cravings for most of the different nutrients we need. That is how people ate a balanced diet in history even though it was much harder to do back then, peasants craved meat and vegetables even though it was easier to just eat potatoes for calories.
I think there’s a distinct difference between what people are describing as “food noise” and a normal appetite.
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.
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".
I can link to Wikipedia too. Which part is the straw man?
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.
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.
I'm not advocating for a crazy diet. I'm just saying people ignore the basics and assume that healthy food has to be miserable. Small changes add up and make a big impact.
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.
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.
You can use the drug to loose weight while trying to understand the underlying problem.
Looking at this a different way, maybe the discipline / self-regulation needs to be applied at the societal (not individual) level, to improve the environment in which we all live?
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.
We have decades of research showing this is more in the "excess acid production" realm of things.
It seems unlikely to extend to bariatric surgery outcomes.
> This idea that Americans are genetically pre-ordained to be fat seems like fanciful thinking.
This idea that Americans are genetically pre-ordained to lack willpower seems like fanciful thinking.
This seems like one of those "replication crisis" claims.
> That's why they could stop being fat, if only they chose to.
So they're pre-ordained not to?
I have a loved one who certainly chooses to, to the point of having had bariatric surgery; GLPs have been an important follow-up. It's really not as simple as you make it out to be.
> You don't go from 12% obesity to 40% obesity in 40 years due to a genetic shift, but rather a cultural one.
What if that cultural one is letting the processed foods industry engineer everything to be deeply addicting?
No. I'm saying it's within their power, so they aren't pre-ordained either way. You were suggesting that it's impossible for a large percentage of the population to not be obese without medical intervention, that it was comparable to excessive acid production which is a genetic anomaly and out of an individual's own control.
> What if that cultural one is letting the processed foods industry engineer everything to be deeply addicting?
Sure, the industry bears some blame and is part of the cultural issue, but even if presented with addicting substances, it is both an individual choice to consume them and a collective cultural choice not to regulate them.
Plus, cars and all "comforts" eating into your physical activities?
The timing is just about right to blame it on Reagan, either the theory that neoliberalism leads to "structured stress" or than some environmental chemical got approved in that time frame.
The idea that it being genetic or not should matter is odd? Who cares why people are fat? They inarguably are fat and will by all available evidence be skinnier and healthier on a glp drug.
I fail to see the need for additional analysis or consideration?
Digging into the root cause or petitioning to tweak the food supply to reduce HFCS are admirable, but entirely orthogonal to the questions: "will taking ozempic et al make an overweight person's life better?" and "will making ozempic et al widely available improve America as a whole?"
Having 40% of your population on a lifetime drug seems like it could cause significant issues in the long-term, especially if there are unforeseen longterm side effects. Medical intervention seems like it should be a last resort, not something half the population is subscribed to by default, so if the problem can be addressed by other means, it really should be.
GLP-1s have been used widely for 20+ years now.
Look up what percentage of people take antidepressants. Why don't they just try being happy?
Look up what percentage of people regularly take OTC pain killers, Benadryl, etc. Why don't they just tough it out?
You are only picking on GLP-1s which happen to treat obesity among other illnesses. All of the other medications I listed are treating conditions with non-pharmaceutical interventions, but you haven't stated a problem with a huge percentage of the population using them.
If your problem is with chronic medication use, this isn't the one to pick on. It is insanely effective.
> not something half the population is subscribed to by default, so if the problem can be addressed by other means, it really should be.
What makes you think that these people haven't tried other options. What makes you think this is the default option, and not a later option? Do you think they are unaware of diet and exercise? Do you think that they choose to be fat? Do you think that people that can get PHDs doing world changing science, climb mountains, run Fortune 500 companies, hell - run marathons, are just too undisciplined or stupid to lose weight?
If there's a genuine chemical imbalance that needs correcting, whether that's causing obesity or depression it certainly warrants medical intervention. That should only account for a couple of % of people, however. If 40% of your population is on antidepressants, in other words 40% of your population is chronically depressed, that points to much, much deeper root issues pervading society, and I do not in fact think it's a great idea to "solve" that by drugging up half the population on antidepressants for life either.
> Look up what percentage of people regularly take OTC pain killers, Benadryl, etc. Why don't they just tough it out?
It's funny you mention this because American doctors will in fact tell people who literally need painkillers to function to tough it out, after overcorrecting for a period where they were handing out chronic medication like candy and causing more problems than they solved.
> If your problem is with chronic medication use, this isn't the one to pick on. It is insanely effective.
My problem is with the scale of chronic medication use. Chronic medication is life-saving as a targeted intervention for people who genuinely need it, and I have no problems with that. Using it as a population-wide bandaid for every societal issue instead of fixing root causes is bound to end poorly, though. What happens when 50% of the population is on some cocktail of GLPs, stimulants, painkillers, sleep meds, and antidepressants simultaneously because it was deemed easier and more instantly gratifying to prescribe chronic medication for everything than addressing any actual causes?
> Do you think they are unaware of diet and exercise? Do you think that they choose to be fat?
I think they are perfectly aware of diet and exercise and mostly choose not to bother because it has become culturally accepted to disregard one's own health for the joy of a Big Mac and a Coca Cola or 15. It is worth noting that the obesity rate for Asian Americans is only 16%, despite being exposed to the same environment and food industry. Did eg. caucasian American genetics take a nosedive in 40 years, or did they just normalise being self-indulgent to an unhealthy degree? I think one of those explanations is more likely than the other, even if it's not something they'd like to hear.
Don't you then start trying to figure out how you can reduce the uses of those precriptions, while maintaining the health figures they're helping to produce? Isn't the answer to do something better than doing nothing? Work with the problem in front of you? etc.
I dunno. What happened when 99% of the population got the polio and measles vaccines?
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.
For many people food is one of the few things in life that gives them some form of joy. I won’t ever take any drug that will take that away from me. Life is depressing enough as is.
What we need is a weight loss drug that lets you eat unlimited amounts of food, preferably even suppressing the feeling of fullness, without gaining weight.
They don’t stop eating, just overeating. Getting joy from food is different from self medicating with overconsumption. (For the record, I love food. I also don’t have an issue maintaining a healthy weight and physique.)
I am on GLP-1 (Zepbound). I have done Weight Watchers multiple times. I'd lose the weight for a little bit, then it would come back. The reason was _I was hungry all the time_. It's not sustainable. As someone else in WW told me: "The easy bit is losing the weight. The hard part is continuing to eat that way your whole life."
It's simply a faulty hunger sensor in my body. It was not what I was eating, simply how much.
GLP-1s fix the sensor. It's really simple. Nothing else to it.
I still enjoy food (although my palette has turned away from anything greasy, which is for the better anyway), but I can finally understand why someone would eat half a plate of something and say "I'm good" and actually mean it rather than trying to diet/starve themselves.
I was able to drink an Italian soda this week and not feel like "oh God I'm drinking my calories I'm going to be punished for this on the scales later".
Sure, I don’t get the instant giant dopamine spikes from binge eating $30 worth of Taco Bell or a couple large pizzas. Once in a while I do miss that, but I can still do it now that I’m a few years into the weight staying off. It’s just not worth how shit I feel the next couple days afterward.
But healthy Whole Foods? What was once kind of meh for me is now something I look forward to and explore. Both going out to foodie type spots, and cooking at home. Both gourmet and basic. Just tasting the nuances and everything in some well prepared veggies or whatnot is great and not something I used to appreciate.
I also don’t constantly feel like crap with stomach issues either. I suppose there is less “addictive” type vice enjoyment in my life in some way, but the tradeoff has been life changing. I certainly still get plenty of joy from many of my meals when I feel the need!
Totally transformative.
I'm pretty sure when food goes right through me that I'm not getting any of those calories. Otoh, I have some idea of what types of foods (and how much) will trigger and the foreknowledge of that certainly reduces the joy of eating some foods I otherwise enjoy.
I still have trouble with calorie balance, but although I enjoy many kinds of ice cream, I have no problem going into an ice cream shop with friends and not ordering anything, even if I'm hungry. A 'single' scoop is way beyond my limit, and if I order a scoop, I won't order a scoop, take two bites and toss the rest, I'll eat the whole thing, so it's not worth it.
When I was doing bike commuting with real hills, I could eat anything, but now I work from home and can't convince myself to put that much time in the saddle just to eat whatever.
This is the problem to be addressed, not hoping for a miracle drug that will let you chuck down 5,000 calories a day and be healthy, imho.
Woe is them I guess for their chemical dependence.
There's metabolism, food density, food availability, psychology, culture, economics, etc in play, but it's important not to lie to ourselves that the proximal cause of obesity isn't from over consumption.
I dislike the rejection of evidence. These drugs solve a problem. Preaching personal responsibility does not. In that way it almost reminds me of drug prohibition and abstinence-only rhetoric.
Yes. Specifically, how basal metabolism is not a consciously-controlled rate that modifies itself against diet and exercise to the point that in some people with serious metabolic syndrome it may be impossible for them to lose weight through diet and exercise without suffering nutritional shortfalls.
Also, the clinical evidence around what works for people losing weight and getting healthier and what doesn’t. Like, I get we have a powerful fast-food and sugary-drinks lobby in America, but wow is it wild seeing people get uppity about third parties’ private healthcare decisions like this.
The average person does not understand how weight loss works; many people do not know the concept of maintenance calories, and don't know how calorie surplus or deficit works.
Simply putting them on drugs for life isn't a solution. The average person does not have metabolic syndrome, yet the average person is increasingly becoming obese or perhaps already is obese in many countries.
Plenty of people are on drugs for life for a variety of things that have less health impact than being overweight.
It literally is "a" solution.
The questions should be: is it the best solution that currently exists? And is it the best that can exist?
It may be that widespread availability of weight loss drugs that actually work ends the economic incentives to promote foods which themselves promote over-eating.
Or it may be that it triggers an arms race with food manufacturers seeking out things that override the weight loss drugs.
Or there may be negative side-effects we have yet to learn about, like there have been for so many other things that previously seemed amazing or miraculous.
That said, 2026 US GLP-1 healthcare sales projections run between 60 and 100 billion [1]. it will be interesting to see if these miricle drugs can really provide that much benefit/offset that much cost.
For comparison, Medicare part D is ~150 billion in its entirety. https://evolvancemarketresearch.com/reports/glp-1-weight-los...
The payment part is almost entirely pushing against GLP-1 agonists. Nobody has a long-term financial stake in patient costs to care that lifetime costs will likely be lower; insurers are just looking at the next couple years against expected churn. Another cost of tying health insurance to employment.
Why I ate too much is uninteresting to me. I also don’t have some moral hang up over it. Give me that easy button all day long so I can focus on shit in my life that actually matters.
If it makes someone feel better about themselves to believe in woo-woo science that violates the laws of physics and ascribe magical properties to GLPs, why do you care?
Why we should not care about putting people on drug who do can benefit from making lifestyle changes, being less sedentary and leaning about maintenance calories and how calorie surplus and deficit works?
if there is no resistance, simply prescribing GLPs to average person may become a new normal.
Because it's useless advice that doesn't work in practice. As witnessed by decades of failure, with the only thing turning the tide on the obesity epidemic on a population scale being GLP-1 drugs.
> if there is no resistance, simply prescribing GLPs to average person may become a new normal.
Probably not ideal, but until Western society decides to change from the ground up it's better than the alternative which showed literally nothing but failure. One is something that works, the other is something that will take multiple generations to correct.
I think you are looking at research on obese people but applying it to average people who are simply overweight.
Why is it a problem if there's wider access to these drugs? So far, afaik, there's been no long term major adverse effects, and especially I've seen no reports of adverse effects that extend beyond use of the drug (as has been the case with previously popular weight loss drugs that could injure people's hearts).
We're 5 years since fda approval specifically for weight loss and 9 years since fda approval for type 2 diabetes. That's a pretty good amount of time to find serious problems, although certainly many withdrawn drugs were on the market for longer, ex wikipedia says Ranitidine was the biggest selling prescription drug in 1987, but was found to be problematic in 2019 (apparently a new formulation is available as of late 2025!)
Sure, there are other ways to work on weight, just like there are other ways to work on allergies and exercises some people say are effective for vision problems. But we don't force people to give up pets or move somewhere that has fewer triggering allergens, we let them take allergy pills; we let people use eyeglasses or contact lenses or have their eyeballs adjusted so they can see; etc. There's a tool that's effective for many people, why not use it?
I spent every ounce of effort I could muster last year to lose weight and dropped 36 kg, however there was never a point where that got easy to maintain, where my body wasn't screaming at me to eat. Crying oneself to sleep from hunger after walking 20000 steps per day is not how I could live the rest of my life. I understand that that is not the case for you, but you must understand that hunger and food cravings are not the same for all people.
There are people literally starving to death because they can't force themselves to eat and of course many more people eating until it kills them. How can you not realize that you happen to be naturally in between these two extremes?
Basically, you walking 20,000 boosts your maintenance calories up, since
deficit = tdee (maintenance) - intake
Once you've lost the weight, there is no need to maintain "deficit" to stay at that weight when you do not understand something as simple as this. I’ve no doubt what you did was perhaps over-restrictive, which made you suffer.
which means no you do not need to walk 20K steps for life, nor you need to perma lower your calorie intake, you just need to eat at maintenance calories after getting to your target weight.
>There are people literally starving to death because they can't force themselves to eat and of course many more people eating until it kills them.
They are rare, so rare i don't run into them at all.
so what?
Until starting tirzepitide I always thought about food, now I don't. Had depressive issues since I was a teenager as well. I took Wellbutrin for 20 years and had an interruption in the last six weeks due to an insurance issue. Payed for the tirzepetide out of pocket, take that once a week, my depression is manageable without the Wellbutrin for the first time in my life. I'm still going thru depression, but that's due to my husbands death in early March. If I wasn't taking my weekly shot I would easily be morbidly obese and probably suicidal. The cost isn't an issue either, I would spend more on food that I'm not buying or eating each month than it costs to buy the medication.
Just because something might not be interesting to someone doesn't mean it has no value. I have no interest in sports, but that doesn't mean they shouldn't exist. I could argue they shouldn't be as prominent in society but that's a different argument.
If you have struggled with your weight, depression, have early warning signs of cardiac problems and a range of other conditions it can be worth considering semaglutide or terzepitide. As long as you stick to the lowest dose that's effective the side effects are minimal to non existent. Categorically dismissing these drugs is as silly as refusing pain meds because "god designed us to experience pain".
So I'm not sure your first sentence is universally accurate.
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.
It’s possible to ignore sadness as well as hunger.
This is all that needs to be said and this is also not that profound of a point. It's literally just harm reduction.
Why do people have such a problem with harm reduction? Why do they feel the need to feel oh-so-smart and point out "weeellll acccktschually there is still some harm so its better if you didn't need the harm reduction therapy and instead just i dunno magically not require it"
Not understanding calorie balance, not understanding calorie density of the food they eat.
How many people know 1kg fat = 7700kcal that if they could create deficit of 7700kcal they could potentially lose 1kg bodyfat? Ofc, i know the relationship isn't that simple but for most people this roughly holds true.
If you are eating granolas in breakfast, it may come across as a shock how many calories they pack, go ahead look it up many people believe that's a low calorie health breakfast option.
Many people don't know
1g of carb or protein = 4kcal
1g of fats = 9kcal.
If what you actually mean to say is "you're wrong, there's no way you could eat like that", the response is "give me nothing but heads of lettuce with salt and pepper, and there are days when I could still continue eating them the entire day whenever my stomach isn't literally full".
People with that low of maintenance calories are usually sedentary and undermuscled.
I think I'm not the ignorant one.
>I've been on a diet since I was 12 years old, and am now approaching 50. I've lost and regained the same 60lbs about 4 times now
You can lose weight by crash dieting, which does not prove much. The first thing that comes to mind for people is simply: "I'll just eat very little and lose weight." It even works, but people quickly get results; it makes them miserable, and they gain it back.
People get stuck between "eating too little" and "binge eating".
>I have logged every bite that goes into my mouth, and lived with a constant hunger for as long as I could take it
This proves you are sincere in calorie tracking, but it doesn't tell us much about what kind of deficit you were in. What were your maintenance calories, and how did you calculate them?
What kind of deficit did you run over what time period?
In my experience, while people know all these things, execution still requires knowing all the "gotchas".
Going from 2700kcal calories to 1000kcal a day diet will make anyone hungry and miserable.
In my experience, people that think they know all the "gotchas" don't really know as much as they think they do.
Knowing fat is calorie dense is great. Without context one would attempt to try to cut it out of your diet almost entirely. Sort of like what literally happened with the food industry in the 80's/90's and 00's.
But then they would wonder why they are so hungry and likely consuming more sugars. Which is even worse for most folks due to glycemic index and how that interacts with hunger.
A little bit of knowledge can be actively harmful. Common sense on this topic actually does far better than most who think they know better. Almost everyone knows what "healthy food" looks like without needing to know anything about much else. Education is not the issue.
https://www.reddit.com/r/tirzepatidecompound/comments/1omfgx...
which is often shared on fitness subreddits, nowhere it asks people to completely stop eating fats.
furthermore i run dieting app with thousands of users so i am not the one who is going to promote zero sugar or fat diet.
My app: https://macrocodex.app/
it's an ad free, subscription free app, i don't make money from this.
I highly doubt this. A lot of people think stuff like juice smoothies, granolas or dates are healthy. Or more generally organic or grassfed or "no added sugar" or "high-protein" high-sugar or "unprocessed" stuff.
People are actively misinformed about what's healthy by a constant bombardment of ads, fads and "common sense".
People tend to not want advice when they're not seeking it, and when someone wants to dissect every detail of what they've done that hasn't worked, when they mentioned it merely as an anecdote, it tends to be perceived as condescending.
About advise part, I am not looking to offer him any advise I am simply defending the method and ideas, so that other people can find success with it similar to what I've done for me and for many others.
How much weight did you lose, and how long have you kept it off?
Giving up the very difficult route of changing lifestyle for the easier alternative of taking drugs for weight loss comes with both biological and social consequences.
The people talking about that shouldn't be bullied to feel ashamed of not taking or recommending taking drugs.
The unbelievably low success rate of diet and exercise programs for long-term weight reduction is widely documented and quite consistent with the earlier poster's experience.
where is your data from? what protocol did they follow?
Curious: how big of a calorie deficit did you run, and what was your macro (protein/fat/carbs) balance.
My personal experience is going low on carbs (especially added sugars) and high on fiber and protein made running a deficit suck much less in terms of feeling satisfied.
Also, a 10% deficit was okay (I was hungry but could mostly ignore it). A 25% deficit was very annoying and about as much as I'd care to do.
For some people, diet and lifestyle changes help control blood pressure. Other people need to take meds for the rest of their lives, anyway. We don't shame them for it.
But this intelectual knowledge doesn't really help if your body is telling you it's hungry all the time and it's hard not to eat something. Better choices can help, because different calories deliver different satiety; but some people don't get much satiety no matter what they eat.
Calories in vs calories out is true, but it's very hard to measure calories out, so it's sometimes helpful and sometimes completely unhelpful.
These drugs seem to help a lot of people in different ways, but if the underlying issue is that they don't get the satiety signals they need to eat healthy amounts without it, of course it's not surprising that when they stop medicating, they stop getting the satiety signals.
There's a lot of variance among humans, but everybody seems to want a one size fits all approach to eating. That doesn't work; you have to find all the things that work for some people, and then try the most promising options until you find something that works for you. Many people crave novelty, and anyway people change over time, so something that works for someone today might not work for them next year, etc.
Maybe try to figure out why you’re feeling hungry. Is it because you’re running a 1000 kcal deficit?
Can your body really tell whether you ate 200–300 kcal less today than you did yesterday?
Most of us can easily notice a 1000 kcal difference, but very few can reliably detect a day-to-day difference of just 200–300 kcal.
What are your maintenance calories? Are they around 1800 kcal, where even a 300 kcal deficit puts you on a 1500 kcal diet? That’s very little food for many people.
In that case, it may be better to focus on increasing your maintenance calories by becoming more active in daily life.
Deficit = TDEE - Intake
either drop intake or boost tdee or do both.
If you managed to boost your tdee to 2500kcal, now a deficit of 300kcal means you eat 2200kcal day to day and 2200kcal isn't very little food making diet easy to follow.
>There's a lot of variance among humans, but everybody seems to want a one size fits all approach to eating.
I think there isn't as much variance as people like to believe, how many people you see walking around you with 3 eyes? and 4 hands?
I know several people who are feeling hungry because they're not dead, regardless of how much calorie surplus or deficit they have.
We can do the same activities and eat the same meals and I'll be satied and they will be hungry. Or I can confuse the hell out of them when we do some big activity and I say "i'm not hungry, we worked too hard"... or when we miss a meal by several hours and I tell them "I'm not hungry anymore, it's been too long... but I should probably eat something"
> I think there isn't as much variance as people like to believe,
Oh sure, I don't think everyone is really a unique snowflake, there are patterns. You can find lots of people in these threads who have a broken hunger sensor. You can find lots of people in these threads that can manage this intellectually. I don't see a lot of people in these threads like me who keep a healthy(ish) weight because IBS punishes them for bad food choices, but I'm sure they're out there. Plenty of people out there where celiac drives their relationship between calories in and calories out.
Diet research would be a lot more interesting if there were ways to classify people by their 'metabolism type' and then see what can work for which type. Maybe there would be more reproducability that way, too.
Are you saying 1000kcal vs 200kcal deficit makes no difference?
>Diet research would be a lot more interesting if there were ways to classify people by their 'metabolism type' and then see what can work for which type. Maybe there would be more reproducability that way, too.
You can easily track your maintenance calories, by tracking your weight vs intake overtime.
For a lot of people, the reason they feel hungry is because the way their brain works is that they feel better when they feel full and their life sucks for some reason, so they want to feel better. Hence overeating. It’s entirely a psychological issue for a person like this. Counting calories is not going to help them. In fact, them even being able to maintain a calorie counting regime is downstream of resolving their anxiety/stress/depression. In other words, diet and exercise are not the beginning in the causal chain required for them to lose weight.
And you’re getting absolutely no traction in this thread because you’re completely oblivious to this. Which is common for someone for whom diet and exercise is easy to control.
i am not trying to gain traction, i already know what i am saying applies to vast majority of people and i've yet to come across people who feel 200-300kcal deficit is impossible to apply for them because of their insane appetite.
In most cases where people say this, they are sedentary so their TDEE is very low, applying deficit makes them end up in very low calorie zone where they feel miserable.
Why all these people who are failing can't actually define their fitness journey by putting some numbers into perspective?
because they calculated nothing, they just winged it. I am not denying that there aren't people who cannot control eatingg, there are but they are rare.
I regularly hear from overweight and obese people who come to me, “I’m genetically predisposed to being fat.” Yet after a few months, we often make significant progress.
Many of them have also tried “deficit dieting,” and it didn’t work for them. But when I looked more deeply into their methods, I found they had calculated their maintenance calories incorrectly.
They were running huge, unsustainable deficits. They weren’t doing any Zone 2 cardio, which is an easy way to boost maintenance calories, and most of them were largely sedentary.
Many times, their diet consisted mostly of packaged, processed foods, and they weren’t eating enough protein or healthy fats or vegetables.
Simply fixing these issues led to major transformations. I’ve yet to come across someone who is truly resistant to these changes.
I do not doubt existence of people who simply cannot sustain even a small deficit or people who have no control over their diet but i've among 1000s of people i worked on i never found even 1 such person.
I keep an open mind maybe i'll eventually find such person, so far i've not.
For me I always feel hungry. Always ready to eat more. Always.
It doesn't seem to matter what I eat or how much, I have no "off switch" apart from maybe being asleep. I sit at big family meals like Christmas or thanks giving and people around me are all "man I am going to pop if I have another bite" and yet I am still reaching for more while simultaneously thinking about what is for dessert. Once I start eating for the day, that's it game over I am going to be thinking about when I can eat next the entire waking time. I have done calorie counting for years (with deficits of usually around 400-800, tracking macros etc making sure I get enough protein) and am fairly active (running 20-25km a week, strength sessions 1-2 times a week) but even when I am not counting calories or especially active that doesn't stop me wanting to eat the whole damn time.
Dieting or not, exercising or not, it makes no difference I am always ready and willing to eat more. I am in a constant mental state of food binge.
I usually stop eating when the food physically runs out on my plate, so portion control when making meals etc needs to be airtight. I work at a BigCo where there is unlimited free food at every turn, so just going to get a coffee is a nightmare as you can imagine as I am surrounded by things to eat. Like e.g. on a bad day I might end up having 6 or 7 bananas a day just to avoid picking up a chocolate bar or donut instead. It's nuts (..and yes there are nuts too and also too easy to just grab a handful...)
I think of it like an alcoholic. But an alcoholic can "go sober" and just cut it out and not get that first taste that leads to the spiralling binge. I've got to eat to stay alive though so every day I "fall off the wagon"
I am seriously considering the pill form now that is a thing. The refrigerated injections just seemed like they were incompatible with a normal busy life with travel etc
It's totally overwhelming and often hard to concentrate with this constant overriding urge to think about eating all the time. It's like gravity, inescapably pulling me in.
People say "Oh I forgot to have lunch!" and it simply does not compute for me. How can someone forget?! Having lunch is my overriding constant nagging thought since having that last mouthful of breakfast. It only stops when I get to start thinking about eating dinner as soon as I have stopped eating lunch. Repeat. Every moment of every day. Eat. Eat. Eat.
It's a like a stuck record or whatever. Over and over. I want to turn it off.
I'd get it if I was solely existing on a diet of junk food that is designed to do this, but I am not. Since I've been tracking every last gramme of food I've been eating on and off for well over a decade I can tell you that it is very much "healthy" and low in processed and/or junk foods. I just never feel full and want to eat more.
Everyone knows what they need do to loose weight.
The problem is we have an environment that in every way promotes over eating and eating hyperpalatable food is pleasurable in the moment.
Yeah, humans should have more free time and do enough work or exercise each day to keep their body in shape.
Why would you eat 2700+800 = 3500kcal? when you can do with 2700kcal?
There are a million reasons like this. You need quite consistent motivation in order to not overeat; overeating is the default for most overweight and obese people.
This is similar to how most people drink alcohol occasionally, maybe sometimes get drunk at a party and even enjoy it, would even be unhappy to have to significantly reduce their alcohol consumption (e.g. when taking some medication) - and yet have nothing similar to alcoholism, might go weeks without drinking without even noticing, and would never even consider having a drink before work.
I've helped many people lose weight, become jacked, and go from underweight to a healthy weight. I regularly hear from overweight and obese people who come to me, “I’m genetically predisposed to being fat.” Yet after a few months, we often make significant progress.
Many of them have also tried “deficit dieting,” and it didn’t work for them. But when I looked more deeply into their methods, I found they had calculated their maintenance calories incorrectly.
They were running huge, unsustainable deficits. They weren’t doing any Zone 2 cardio, which is an easy way to boost maintenance calories, and most of them were largely sedentary.
Many times, their diet consisted mostly of packaged, processed foods, and they weren’t eating enough protein or healthy fats or vegetables.
Simply fixing these issues led to major transformations. I’ve yet to come across someone who is truly resistant to these changes.
I do not doubt existence of people who simply cannot sustain even a small deficit or people who have no control over their diet but i've among 1000s of people i worked on i never found even 1 such person.
I keep an open mind maybe i'll eventually find such person, so far i've not.
Note that I'm not speaking as someone who has just accepted being overweight/obese. I was hovering around 105kg in my early 20s, then I gathered the motivation to go down to ~75kg over the course of a year, then maintained myself around 80-85kg for the next 5 years, then in a bad period went back to overeating and was hovering around 100kg again for a few years, and now I'm in the process of going back down (currently around 86-88kg after 6 months of actually working on losing weight - so about two thirds of the way to where I'd like to be, given I've also been building some muscle mass).
So I'm not someone who just throws up their hands and says "I'll always be fat", or maybe pushes themselves for a fad diet one month and is proud of losing 5kg that come back right away. My experience though is that appetite control and managing food cravings are the most important parts of managing my own weight, and that the nutrient content of food has virtually nothing to do with it. I can eat a whole steak with 400g of steamed peas and some asparagus, with some butter and cheese, and then feel hungry and unsatisfied 4-6h later when the stomach isn't as full. And if I'm not in a good headspace, I may well then grab a McDonald's menu to get rid of the feeling of hunger and get some satisfaction that the steak and vegetables didn't actually address on that day - and the exact opposite can happen on other days.
This is why for me things like One Meal A Day (OMAD) has been mucn more useful than actual careful nutrient tracking. Being able to tell myself "it's OK that I'm feeling hungry right now, I'll eat that X tomorrow and be satisfied" has been the single biggest helper. I've not yet been tempted to try out GLP-1s (afraid of the side effects, the food problem isn't that bad), but I imagine they could be a huge help if they removed the need for such willpower-based mechanisms.
From my experience stuff like Intermittent fasting, OMAD is not really needed.
Something especially useful to many people is being able to visualize, their maintenance calories vs calorie intake, see this: https://macrocodex.app/assets/hero-tdee-line.png
When dieting properly, you should focus on long term weight trends rather than daily fluctuations.
Yeah I know bodybuilders manage to get jacked and many of them are doing nothing but maintain their body and are taking anabolic steroids and thyroid hormone and stimulants and who knows what.
People in pro sports take PEDs.
>can be very physically active and muscular but still pretty fat.
you can retain higher muscle mass at higher bodyfat% like Sumo Wrestler.
being lean limits amount of lean mass you can carry.
>Yeah I know bodybuilders manage to get jacked and many of them are doing nothing
bodybuilders who take PEDs do not easily gain fat because steroids change nutrition partitioning.
also, some bodybuilders take DNP, clen, t3 etc... but many bodybuilders also do hours of zone2 cardio.
operative phrase in that sentence "how they live". They need to live more active lives. And that's better than a weight loss drug because inactivity causes systemic disease beyond weight gain.
GLP-1 drugs do to hunger what pain meds do to pain, but if you're overweight and your back is aching because you're sedentary the solution isn't a cocktail of drugs, it's to get off your ass, because that lifestyle is going to cause you biomechanical, metabolic and even cognitive issues down the road.
There's disease you can't do anything about and need to treat with medicine, but if you're experiencing symptoms because your lifestyle is abusing your body change your life. There'll come a moment where there's no wonder pill to fix your issues and in that moment you're better of if you know how to actually get control of yourself. Which most import of all is going to give you the confidence that you can change. You don't want to be 50 years old and your only cope in life is praying that a pharma company mutes whatever symptoms plague you.
When I become more active, I also become more hungry due to the extra energy consumption. The net effect is little weight loss and more often than not weight gain. While being physically active is beneficial to health in many ways, it does little for losing or maintaining weight, at least for me.
Active life = higher TDEE which means you can eat more food while still maintaining same deficit.
For example, a lifting session may burn 200-300kcal and then they'd think they've burned a lot, so they will end up eating 500kcal back.
so as a result there is no deficit there.
Even people who track their calories perfectly often eat when hungry because it is the most basic of human instincts and our brains and bodies are wired to respond accordingly.
>Even people who track their calories perfectly often eat when hungry because it is the most basic of human instincts and our brains and bodies are wired to respond accordingly.
Many people can track calories, hardly any of them are tracking calorie burn and no the ones from your watches or displayed on cardio devices aren't correct.
Many times the eating more issue you are seeing is because average guy may estimate that 1 lifting session burns 800-1000kcal. How do i know? i've asked random people in gym this question.
It is hard to accurately calculate the calories burned in a lifting session but the ability to count calories has little to do with the causes of obesity. Even if a person could count them perfectly that doesn’t mean they are capable of manipulating the numbers to meet their goals.
If you live in a place where waking to get your daily life needs met is possible, good for you!
Personally, I look at GLP-1 agonists 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. That said, it's not one or the other, it's always great to be more active.
Also that's how my mum got it in the swiss test run. It was never supposed to be long term, just to help change eating habits.
Why would this sentence make any sense?
I stand by my words that just using Ozembic without changing your habits on the way can't be the right way. And as far as I know studies suggest that that is actually the case. Like with any diet really
That's a semantic argument. The "issue", medically, to most people viewing this as a health problem, is excess body fat and not eating behavior.
I mean, you're not wrong, but this seems silly. YES, it would be better to have developed a cure for disordered and unrestrained eating. We didn't. And we don't really even know how. Oops, as it were. But we do have a treatment that avoids the most significant impacts of those problems.
Medicine is harder than software engineering. Not all bugs are shallow even with all the eyes in the world.
It would be an incredible advancement if we figured out a reliable and replicatable way to just eat less food, but until then I think a drug that makes you do that is pretty decent.
Yes, obviously. Which is why sustainable weight loss takes a commitment to making a change in lifestyle.
What’s more sustainable, changing your lifestyle to maintain the weight you lost, or being beholden to taking a drug to maintain that same lifestyle change for a hope at maintenance?
We’ve tried shaming people into being healthy. Amazingly enough, it doesn’t work very well.
It could definitely use more support, but it doesn't do a ton if the structure of people's lives is being changed by other factors. (Car based commutes, long work hours, lack of exercise at their job, the cheapness of certain kinds of foods, food advertising.)
If we had a lot more political power to work on public health programs, maybe. But obesity rates are rising throughout the developed world regardless of local culture so there is a ton of work needed there.
Well-studied problem.
It makes more sense when you realize that something like sheer dieting/exercising willpower isn't why some populations are skinnier than others. Pick another country with a healthier-weight population, start placing some of them in the US, and they'll gain weight. Put them back, and it'll drop again.
If "just diet and exercise" (the advice, and individual effort to that effect) aren't what are keeping some populations skinnier, why would it cure a population with an obesity epidemic?
Just off the top of my head the food (portions, quality, etc) in the USA combined with how much people no longer can walk vs being required to drive are a huge contributor to weight gain of immigrants to the USA.
There are of course other decisions that might help cope, like moving to one of the few walkable cities we have or structuring your life to reduce the lifestyle, but those all have a lot of other effects like completely upending your current life.
What’s a person supposed to do about a problem that’s probably tangled up in several major areas and would require large reforms across the economy? We can’t even get mandatory minimum paid leave or healthcare for everyone (both of which might well be components of fixing it “right” anyway!)
This is likely a problem that spans our food culture, business culture, economic structure, built geography, and social benefits system, among other things.
You can spend a lifetime fighting those and be fat the whole time because despite massive effort and objectively incredible achievements you and your movement only got us 5% (that’s a lot!) down the road towards fixing these things, in fifty years.
Or you can take a weekly shot and be well on your way in a month.
Working on the “real” fix is definitely something we should do (it’s not like the causes of this aren’t causing other things to suck, too) but even people doing that would probably like something available that they, not just their great-grandchildren, can have.
That's some pretty... charged language. But even so: the drug, clearly. People take drugs reliably as a matter of empirical fact. People likewise emphatically don't "change their lifestyles" as a general rule. If they did we wouldn't be talking about this new drug, would we?
People take drugs if they can afford them; will GLP-1’s be available dirt-cheap to the masses or limited to those fortunate enough to have health insurance.
(For comparison: Countless scores of diets are discontinued daily.)
Meanwhile: Diets have been discontinued by people of all income levels for as long as we've had diets to discontinue. Some people succeed with their diets, and some don't.
I don't even know I read this board and all the fucking dumb opinions.
Their R&D is directed at treating common chronic conditions with drugs that you have to take forever. That's what makes them money. Treatments for rare conditions or true solutions do not. It's just economic incentives.
That's also why when they do develop something for a rare condition, it costs you a bankrupting amount of money if you need it.
And anyway, demonstrably not true given that pharma companies are working on a number of drugs that are one-and-done treatments for things like Lp(a). We should figure out a way to make them fabulously wealthy for achieving breakthroughs like that even without a lifetime prescription.
You: The drug is a bandaid; just make good food choices.
Antidepressants are the best analogy here. If the core problem is in your brain (or brain-body integration), then, for now, exogenous compounds are the only way to address the core issue.
Not a doctor, but I would at least try to look into this. Best of luck!
You’re not providing anything of note, so merely saying “I’ve looked into it. I’m good” seems like it’s the correct reply.
Long term PPI use has non-trivial risks, including magnesium and other micronutrient deficiencies, and can lead to things like SIBO and other primarily gut related morbidity.
I would definitely suggest sitting down with your doctor if you were not specifically instructed to take it for that long.
I’d recommended getting up to date knowledge about the options before providing advice on them, starting with safer h2 antagonists like famotidine.
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.
Oh, there’s consequences? One of those is an almost universal weight gain measured in the dozens of kilos? You want help with that?
Sorry, it’s against Calvinist/puritan morality to help you with that by providing a medicine to counteract that. You need to do it the hard way (regardless of the statistics that show you will just be obese now until you die thanks to the meds which, I maintain, that you must take).
Wow. I had no idea.
Come on, why is it that whenever GLP-1s come up on this site, the comments are filled with people helpfully pointing out this fact as if no one knows it already?
First, I don't personally have it out for GLP-1s specifically.
Second, here's the thing about side effects: there are a good number of examples across multiple categories of drugs showing that some people experience side effects doctors and pharmaceutical companies have insisted aren't real or are exceedingly rare, with evidence later showing this not to be the case.
For instance, there is a growing body of evidence that a subset of people who take SSRIs experience life-altering sexual dysfunction that persists long after the SSRIs are discontinued. Up until fairly recently, that this was happening at all was basically dismissed by all but a small number of practitioners. Now, there's a name for this and even some warning labels.
In the US, which is only one of two developed countries in the world that allows pharma companies to advertise directly to consumers, there are huge incentives to minimize side effect profiles and even to bias clinical trials so that benefits are exaggerated and downsides are underestimated.
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.
My experience was about antihistamines, which are definitely effective.
My impression was it was weekly at first for 1-few months then monthly for like 5 years.
Wish i had started like yestercade :(
In any case, it's worth doing the skin prick allergy shot testing so you can have some idea of what common allergens affect you and the intensity of each.
GLP1 agonist type incretins have been available for over 20 years at this point. The first marketing approval was in 2005 for exenatide (Byetta), indicated for T2DM. Exenatide was the first in class for GLP1 agonists. Then came Liraglutide (Victoza) for the same indication around 2010, and received marketing approval for weight loss (as Saxenda) 4 years later. After that around 2017 was semaglutide (Ozempic & Wegovy).
T2DM is a chronic disease, so patients who started exenatide had to stay on it life long.
These drugs are nothing new and were already being used for T2DM. It only caught public attention because semaglutide achieved double the mean BW loss over liraglutide, making it meaningful for weight loss. Novo Nordisk first got approval for Ozempic for T2DM in 2017 and then received approval for it to be marketed for weight loss under Wegovy only in 2021, but by then clinicians were already prescribing it off-label, strictly speaking, for weight loss.
I don't know how much we could extend this "they've been around for a long time" to tirzepatide (Eli Lilly: Mounjaro & Zepbound) because it's the first dual agonist. It targets GLP1 and GIP, and thus it's meaningfully separated from the others. This goes for retatrutide (again Eli Lilly) as well if it eventually comes to market as it would be the first triple-agonist targeting the aforementioned + GCGR, the glucagon receptor.
After discontinuation, most patients regain around 60-80% of the weight they've lost with the medication - but this figure is limited to the study duration, so the weight regain might have continued beyond that. A good starting point for dipping your toes into outcomes would be the STEP and SURMOUNT trials, these were the trials they did for marketing approval. (They did multiple rounds of these, I believe STEP4 and SURMOUNT4 specifically had groups that stopped therapy mid-way).
We see this rebound effect with weight loss mediated solely via lifestyle modification as well, however. Still no idea why. Very broadly speaking, only a small proportion of obese/overweight patients will manage to keep the weight off, and the rest of the patient population tends to be divided into two groups: those who regain most of it (usually around half of the lost weight will be regained within 2 years, and 80% by follow up year 5), and those who regain more weight than they had lost. There hasn't been a way to tell preemptively which group the patient will land in at the time of beginning of lifestyle modification.
On top of this, yoyo-ing is also a phenomenon we tend to see. Obese and overweight patients who've managed to lose weight once will regain, lose again and so on. This phenomenon is associated with worse outcomes than being obese alone, so it is important to do long-horizon thinking when initiating therapy (be it lifestyle or pharmacotherapy) e.g. is the patient willing to stay on pharmacotherapy indefinitely? what about an indefinite maintenance dose if the patient succeeds with lifestyle modification alone? has the patient had lost and regained significant amount of wt prior? etc.
Maybe in America you do, here in Europe I am not so sure about that
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.
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.
> Many people taking these kind of drugs are gambling with their well being. No doubt that in many cases that gamble is worth it.
You use the word "gamble" and it is correct, but the connotation is a negative one.
We take a risk in everything we do. We seldom know the long term effects of anything. Right now I drink tea, and I drink tea quite often. Is this healthy? Does it have long term negative effects?
With GLP-1 medications, deciding to not take one, if you are overweight, is also a gamble. A pretty huge one. Obesity very often leads to type-2 diabetes, and the first step is prediabetes. Should someone with high BMI and high A1C avoid GLP-1 because we don't yet know the long term effects? We do know the long term effects of being overweight.
No, it's really not "pretty likely." These drugs are extremely well studied, have been for a long time across now hundreds of thousands of clinical trial participants over decades.
The downsides of obesity however are immense. Far, far worse than people intuit.
Agreed non-pharmaceutical interventions are preferable when they work. But it turns out – empirically – that it's very hard to implement these successfully.
Think about how we describe contraceptives, medically speaking: a failure rate is tracked and promoted that’s the in the wild rate of failure, not the ideal-use rate of failure (which can be effectively zero!). The diet and exercise equivalent of a contraceptive couldn’t be sold, because its failure rate would be way higher than its success rate.
So “we” (people who’ve paid attention to the science on it) know it doesn’t work (on a population level), like for-sure definitely does not work, but a person reads this assertion of fact and goes “but wait it worked for me, this person must be dumb or something” but that’s not it. It’s two different perspectives on what it means for it to “work”.
Last I checked, researchers in the specific area of high-touch weight interventions were excited that they finally had a tool that might more-than-barely work… in glp-1 agonists.
Informing people that they can avoid pregnancy and STDs if they’d just stop fucking each other doesn’t work at scale either.
However, all the evidence is that the vast majority of people fail at changing their habits in ways that produce lasting weight loss, so it does not generally work as advice for reducing your weight.
So you're technically right, but it is irrelevant, because we don't know how to actually get people to change habits with any meaningful rate of success.
At this point it is downright harmful and wildly unethical to recommend it when we now have a far more successful option.
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.
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.
Without calorie deficit, you'll not lose much weight by lifting alone.
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.
Not unlike if you shatter your legs, your recovery may be long and incomplete.
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.
Source? I thought it was 2/3rds of the weight regained, which is still a substantial long-term loss.
Do you have one you’d recommend reading?
I think people consciously or unconsciously consider being overweight a moral failing and so are quick to point out the flaws.
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
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.
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.
Maybe it's well-known, but I read the starvation response Wikipedia page[0] and didn't grok it.
There's a part of my brain that constantly thinks about food. It's like tinnitus. GLPs stopped that cold.
For me, stopping fast food, most restaurant/takeout food, and processed food such as bread, pastries, chips, cookies, and any prepared/convenient "snack" items drastically reduced how often I felt hungry or just wanted to eat for no apparent reason.
Tinnitus really is the best way I can describe it. I didn't even realize how pervasive it was until it shut off.
What we now call food addiction is exactly what kept our ancestors alive during famines.
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.
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.
When a treatment can’t fail and can only be failed, it’s big red flag for me.
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.
If you ingest less calories, you lose both muscle and fat mass.
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.
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.
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.
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.)
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.
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.
Grey market references stuff like HIMS where you are getting a real doctor to write you a prescription and a shady compounding pharmacy takes those Chinese black market peptides, compounds them, and ships them to your door.
Black market is just going direct to the source in China and getting them for yourself without a prescription.
Even after all that it comes down to like $50 a month at the highest dose.
Cremieux is a popular biohacker on Twitter who has a paid Substack describing the process.
That's enough to get anyone started.
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...
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:
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.
I tried them and my health got massively worse and I couldn’t eat at all, on a sub minimum dose.
I put them just under antibiotics. In terms of quality of life years given back at a population scale.
Edit: the title should have such a tag
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.
Positive or negative, I don't want drugs in my water.
Also worth mentioning GLP1's are known to cause anhedonia. So there's that...
I do notice it makes it harder for me to get up and do certain harder, outdoor chores.
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.
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.
It's all mostly just anecdotal and empirical.
Same with the fecal transplant stuff, which (AFAIK) basically replaces one persons gut biome with a different one. Which causes cravings to change completely for the recipient, in some cases resulting in weight loss.
Which, to me, kinda tells that it's not a willpower or brain thing, it's just the gut biome controlling what you "want" to eat.
What was the downside of washing hands before surgery?
Typically, if something "works", there often appear to be side effects. A free lunch is rare.
https://www.uclahealth.org/news/article/understanding-medica...
Of course we already manipulate brain chemistry in other more direct ways with antidepressants so perhaps any unwanted second-order effects could be minor in comparison to the profile of existing antidepressants .
https://pmc.ncbi.nlm.nih.gov/articles/PMC7105351/
I've been watching developments on how GLP1s seem to go beyond just hunger/insulin response, even how they may affect symptoms of polycystic ovarian syndrome (PCOS), which is difficult on women who have it:
Unless it’s literally a deficit. There isn’t a downside to treating vitamin C deficiency with vitamin C.
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.
That’s not how evolution works.
We evolved in an environment where every bit of food took hours of effort and food preservation was impossible, so the only logical thing to do with extra food was feast and store up as much fat as possible for lean times. We're still many generations away from evolving to compensate for the discovery of fire, let alone everything that came after that.
This is the only way that happen - noticeable evolution is always driven by population bottlenecks or strong selective pressure. In the absence of those, mutation just keeps expanding the gene pool so more different candidates are available for the next bottleneck.
In case an event happens where only red-haired people survive, good thing some are available, otherwise there's no reason to think everyone will have red hair in the future.
https://theconversation.com/how-childhood-infections-requiri...
https://www.scientificamerican.com/article/a-single-course-o...
If you're tired and don't have energy you'll also feel depressed but that doesn't automatically mean you feel tired solely because of depression.
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.
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.
That said, exercise has a direct impact on metabolic health which is pretty necessary to maintain a healthy weight.
This depends on your VO2max/FTP. At very modest 150W FTP it would be ~550 kcal.
> Something you can easily overcome by eating a donut
Don't eat a donut then? It's not like donuts randomly fly into your mouth and you have no control.
>Exercise is absolutely useless for weight loss if it isn't coupled with a controlled diet.
That's obvious. It's not "absolutely" useless as it will take much more effort to gorge on food (e.g. I don't know anyone who would be able to eat a donut after an hour of a vigorous exercise, least crave one) and you also have less time to stuff your face and think of snacks. But it's entirely possible to still overeat while 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.
>Is there any source on this?
Other than the people saying they hate exercise and are glad they can take a drug instead in the comments here? This https://sciencesources.eurekalert.org/news-releases/1130958 for example.
>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.
Is there any source on this?
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.
2. Not necessary here either if dietary habits are permanently altered, which can happen more easily after several months on GLPs.
3. Perhaps!
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?
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
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.
I imagine though that on-balance they'll be net positive because being overweight is just so bad for you.
(Never tried them myself, but very intrigued by them.)
It stopped me cold and has gotten me almost back down at the lowest I was at after my diet so far and I keep losing at a slower pace but basically without effort.
In terms of pleasure, I'd say mostly no with some caveats. I have fewer snacks, and drink less coke, and I enjoyed both. I don't find chocolate or baked goods as enticing any more, but it's not stopped me from enjoying them on occasion.
It's more that it's stopped me from wanting them as often. I find it easier to tell myself not to grab a snack when I'm already full in particular. Before I might overeat to the point of discomfort.
So when I now actively choose to enjoy those things, I'm more likely to actually enjoy the whole experience.
I'd say the exception is probably coke, which I do find less enjoyable.
That's the best way I can describe it. I could basically always eat before and now I just...don't feel like it lol.
I will say, they are rough when you first start out on them. During the 1st 6-8 weeks I had several instances of maaaaaybe five seconds of warning between feeling nauseated and vomiting.
It settles down after a couple months and it was never bad enough to be a dealbreaker, but it's a fun time.
I had to conscientiously try and find new "fun" things in my life to replace food, which used to be my treat/highlight of my life lol.
I notice a little less joy, pizza used to make me soooo happy lol. Now even if I have pizza- which I still totally can, I just accommodate for it, but it's just like... okay, whatever here's some pizza, cool. I can have 1 or 2 slices and feel fine and not go hog on the entire thing and have it be this amazing fantastic binge.
Outside of eating, I drink less, but do have occasional beers. I enjoy them.
And my relationships are not less fulfilling, and I don't find my life and work less interesting. All in all, the only thing I don't like is the occasional "egg" burps I get from it.
For me the pros outweigh the cons, I don't obsess over food constantly, my belt size went down and my watch band closed a few notches and even my dental hygienist mentioned last week my face was thinner. Overall it's a huge win.
I pay out of pocket $450 a month for it and it's worth it. The money I saw from no more online shopping habit and no more doordashing or drinking probably breaks even.
Yes. Why not? A body is a complex biomechanical system, that can be influenced by certain chemicals. Some of them can solve the underlying problem.
Why everything has to be a morality play?
> Why should we believe GLP-1 class drugs are any different?
Why are they any different from, say, antiretroviral drugs? Or from something like statins?
I started the GLP-1 drugs with liraglutide, a predecessor of Ozempic. It works similarly but its half-life is just several hours, so you had to get a daily injection. It has been in use for two decades by now with great results.
I know people who have had miraculous benefits from psych meds. No downside. Using them for years. Or if there is a downside it’s massively outweighed by the upside.
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.
With same dose do you get flat and consistently low appetite or do the effects lose power if you dont up the dose?
My experience has been the appetite suppression goes down after a while but doesn’t go away entirely. With each change in dose there’s always a more pronounced effect in the beginning. I don’t take it for weight loss though, I take it for T2 and my A1C is a 4.3 so it works very well for that and it’s unlikely I’ll change doses again because it’s well controlled.