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Comment by Aurornis | Hacker News Reader

That is the question now. Some studies have some early evidence that GLP-1s might reduce inflammation markers a little more than weight loss alone.

Giving GLP-1s to normal weight people doesn’t work well because they can have to work harder to maintain their weight. That can be a real problem as people get older where maintaining muscle mass is important for quality of life and longevity. I remember how hard it was to keep some of my grandparents at a healthy weight, so adding a GLP-1 to a non-obese elderly group is a no-go for study purposes. Going to be hard to separate these effects out.

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I'm normal weight and am on a low dose (1mg every 10 days) of tirzepatide. I'm able to maintain my weight at this dose, and I've seen improvements in inflammation and other blood markers as well. It's not impossible, it's just difficult to do within the normal health system parameters (specific dosages tested for weight loss, etc.). I use a gray market supplier direct from China and reconstitute the dose myself.

I have no trouble eating maintenance calories at 25.0 BMI on 3.5-4.5 mg/wk of tirzepatide, lol. (1mg every 10 days normalizes to 0.7mg/wk.)

My assumption was that GLP-1's don't suppress appetite so much as suppress the compulsion to eat when not necessary/more than necessary?

It’s both. That’s why it’s so effective.

They also clearly have some impacts on metabolism. It’s well known that a challenge with dieting isn’t just eating less, it’s metabolic changes that make weight loss harder. GLP-1’s avoid that.

They do slow down the metabolism, yes.

They seem to also act on some reward mechanism - making some stuff (not just food. Alcohol, gambling, porn, smoking, other drugs have anecdotally been reported to feel less attractive / addictive) have a reduced pull on one's will. They also measurably delay gastric emptying - to the point that some medicines, meant to be taken on an empty stomach, are not safe to take within up to 3 hours from the last meal, compared to one hour or so for other people.

It’s not clear to me that they slow down metabolism consistently, although that does seem to be the effect in some people.

I rather think the opposite is true, that by increasing signals that the body is satiated in many cases it is avoiding a metabolism slowdown caused by hunger.

> metabolic changes that make weight loss harder

Which are vastly overblown. I diet every year as part of bodybuilding, at a range of intensities and durations, and have never had issues with sudden metabolic changes that make it harder to lose weight.

That’s very nice for you, but it is a phenomenon that is well documented by research: https://pmc.ncbi.nlm.nih.gov/articles/PMC4989512/

It's not as significant as most people make it out to be (also born out by the research).

Your body naturally tries to maintain homeostasis. When you cut your food supply below what your average is, and probably has been for years, your body will fight you in every way it can.

For example, I eat too much and started eating less. I now eat normal portions instead of portions fit for 2 people. I have more than enough food and energy, and yet, I am hungry. The hunger is fake, I certainly don’t need more calories. But my body thinks it does based off of its knowledge.

See that’s the problem. What works for you doesn’t work for others like me that have tried dieting. It’s the food noise that’s the problem and it’s a mental issue. Glp-1 has helped me a lot. The metabolic changes are kind of insane. Even doing keto which did help lose weight didn’t have this kind of effect on me.

> It’s the food noise that’s the problem and it’s a mental issue.

Yes, I've been through this, and I think it's the reason I got fat in the first place. I had a constant feeling of hunger, but which was "fake", as some other commenter put it, since I was clearly eating more than enough.

But I've found that one way to fight this, which at least worked for me, was not just eating less, but eating differently. I increased foods with low calories per volume, such as salads, peppers, peas, and the like, and combined them with some form of high-protein, low-fat meat. This fills my stomach for a good while, and this feeling of fullness chased away the food noise. I just couldn't think about eating anything, since my belly still seemed full a long time after the meal.

That’s nice. Many peoples’ experience differs. Congrats on it working on your computer.

Personally on the whole I’ve had no issues with controlling my weight. I’ve had a couple of isolated instances where I felt hungry all the time and started gaining weight rapidly despite my best efforts. Circumstances changed and it stopped. It sucked and I learned a new level of empathy for the people who get this all the time and not just as a one off.

Bodybuilding, eh? That makes you vastly more likely to believe in bro-science.

"This doesn't happen to me, so clearly it doesn't happen to enough other people to be a real thing."

Also consider that, as a bodybuilder, everything about you that matters to this discussion is significantly different from someone who is not a bodybuilder, which is most people.

What is appetite?

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