Short answer first, then the reasoning. The mechanism is more central than most summaries suggest. Receptor agonism in the arcuate nucleus activates POMC neurons and inhibits AgRP/NPY signalling, and the downstream MC4R pathway is the same one disrupted in monogenic obesity — convergent genetic evidence that the target is the right one. Peripherally there is glucose-dependent insulin secretion, glucagon suppression and delayed gastric emptying, but the gastric component largely adapts over months while the central effect persists, which is why the durable effect is appetite rather than fullness.

Dr.BariatricHTX said:

The mechanism is more central than most summaries suggest.

Agreed, and the adaptation point cuts both ways: tachyphylaxis to gastric emptying is why tolerability improves, and it is also why people who were relying on physical fullness feel the effect fade while the appetite effect is still working.

bbq_ray_KC said:

Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.

Mine went the same way, slower.

Adding the clinical framing, because it changes how the question reads.

bbq_ray_KC said:

...we're creating a generation dependent on cardiovascular risk...

I understand the concern, but consider this analogy: are we "creating a generation dependent on" blood pressure medication? Cholesterol medication? Thyroid medication?

Obesity is a chronic disease with biological drivers. Treating it with medication is no different from treating any other chronic condition. The "dependency" framing implies weakness or moral failure — neither of which is accurate.

If ongoing medication is what keeps someone healthy, that's successful treatment, not dependency.