[molsongolden]

With these drugs, is there any mechanism at work beyond "patients have a lower appetite and eat less food"?

I've only read a few papers and articles but what I've seen is that all of the hormone triggering leads to 1) decreased appetite 2) slowed gastric emptying which also decreases appetite.

Patients lose weight due to eating less but usually regain the weight when stopping the drug since they then go back to their normal level of eating.

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Are these drugs fixing/replacing a system failure where people don't feel satiated normally?

Can the same effect be replicated by eating a higher fiber and higher fat diet with more whole foods to feel full longer and slow gastric emptying?

[quux]

GLP-1 affects a lot of systems beyond just appetite and gastric emptying. For instance it acts in the pancreas to promote insulin secretion. GLP-1 receptors are also found in a lot of other tissues, including heart, tongue, adipose, muscles, bones, kidneys, liver and lungs. The effects of GLP-1 in these tissues are an area of intense research.

[petesergeant]

> With these drugs, is there any mechanism at work beyond "patients have a lower appetite and eat less food"?

Those are definitely the key routes, but I suspect from my experience (and so the do the drug companies!) that there's some kind of mediation of reward system going on there too. Simply put: I no longer get a massive dopamine hit from sugary food. A candy bar still tastes great, but I don't immediately want to eat another one like I used to, even if I'm genuinely hungry. My addictive response to food is gone.

My favourite foods still taste great, I just no longer have to expend all of my energy in not having three portions.

> Can the same effect be replicated by eating a higher fiber and higher fat diet with more whole foods to feel full longer and slow gastric emptying?

No. Like many people who've been on a perpetual diet, I have tried -- at length -- virtually every style of eating known to man. The food noise always comes back. Even before I started, I was eating very healthily as a base-line, mostly vegetables, mostly vegan, mostly whole foods, tracking my fiber to make sure it was high. But I've also tried and sustained for many months keto, paleo, "slow carb", all sorts.

[aantix]

- Tirzepatide may activate brown fat, which might be a metabolic advantage.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396640/

- Another study - there was a 16% weight loss for those that received semaglutide/diet/exercise/counseling versus a loss of 5% for placebo those that received diet/exercise/counseling without semaglutide.

But they didn't control for calories, so it may just be proving that dietary adherence with the medication is better than without.

https://pubmed.ncbi.nlm.nih.gov/33625476/

https://classic.clinicaltrials.gov/ct2/show/NCT03611582

[Shekelphile]

> Are these drugs fixing/replacing a system failure where people don't feel satiated normally? > Can the same effect be replicated by eating a higher fiber and higher fat diet with more whole foods to feel full longer and slow gastric emptying?

I think it simply takes a long time for your body to adjust back to where it should be after a period of extended binging and these drugs make it happen much faster. The only time I consistently lost weight in my life was when I lived in a food desert and had no car and not much money, so I was forced to only buy the cheapest vegetables and meats (usually chicken) and make what I could out of that and make it last for the week. Even then it took more than 6 months before I felt normal eating that way.

Of course, it's extremely easy to fall off the wagon when your body works this way too. Even a day can wipe out weeks of gains and you can always 'relapse' even after months of doing the right thing, and end up stagnating or completely reversing any progress you've made. In a way it seems that food is the most addictive drug of all. You can easily quit alcohol, cigarettes, hard drugs with a couple weeks of willpower (and I have multiple times). You can't ever stop eating food if you want to be around to experience life.