Taking the question as asked, rather than the general version of it. 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.

If somebody has the primary source to hand I would rather cite it than paraphrase it.

BethLabQueen 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.

pam_columbus said:

I have a family history that makes the labelling relevant to me rather than theoretical, and I want to know what it actually rules out.

Mine went the same way, slower. Posting only so the count is not one.

Clinical perspective, offered as context rather than as advice.

Thyroid cancer screening labs for thyroid monitoring — addressing the boxed warning concern with actual data:

Calcitonin level: 3.0 pg/mL (normal <10). Checked at baseline, month 6, and month 12. Rock stable, no upward trend.

Thyroid ultrasound: normal, no nodules at month 12.

The MTC risk from rodent studies has not been confirmed in human post-marketing data across millions of patient-years. The boxed warning is a regulatory precaution based on animal data. While monitoring is prudent, the clinical risk appears to be negligible.