adam_van said:

No disagreement, though it depends on where somebody is starting from, and this thread has been assuming a starting point nobody stated.

Second this. Posting only so the count is not one.

adam_van said:

No disagreement, though it depends on where somebody is starting from, and this thread has been assuming a starting point nobody stated.

Coming at adam_van’s question from a different direction. 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.

The figures, for anyone assembling their own picture. If you are comparing against somebody else’s result, check that you are comparing the same measurement taken the same way. Most of the apparent contradictions in these threads dissolve at that step.

That is the short version; the long version is somebody else's post.

Following on from adam_van — and this may be the naive question:

Which effects tachyphylax and which persist, because the answer explains why tolerability improves while the appetite effect keeps working?

TrialTracker_MD said:

If you are comparing against somebody else’s result, check that you are comparing the same measurement taken the same way.

Pushing back on TrialTracker_MD here. I think the framing smuggles in the conclusion. Ask it the other way round and the obvious answer reverses, which usually means the question is doing the work.