What Ozempic does to the gut-brain axis

>my body and mind are no longer is in starvation mode

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

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

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

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

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

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

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

This sounds concerning to me.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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