Appetite effects looks different depending on whether you are reading the primary literature or the summaries of it, and the difference is not in our favour.
Everything in post #26 holds. The case it does not cover is the one I have.
The useful distinction on appetite effects is between what was measured and what was inferred from it. Both end up in the same sentence and only one of them has error bars.
Receptor occupancy required for a clinical effect is not the same as full occupancy, and dose-response curves flattening at the top is what you would expect from that.
None of the above is medical advice and I am not qualified to give any.
Where I part company with post #40, and it is a narrow parting.
I read the earlier replies on appetite effects twice before writing this, because I had assumed the opposite and wanted to be sure I was disagreeing with what was said rather than what I expected.
Narrowing post #60, because the general version has more than one answer.
Cross-reactivity and selectivity: the compounds are not perfectly selective for their target receptors. Semaglutide has some activity on other receptors; tirzepatide activates both GLP-1 and GIP with different affinities. The off-target effects are part of the overall pharmacology.
Worth reading the earlier posts in this thread before acting on mine.
What I would check first on appetite effects is whether the thing being measured moved or whether the way of measuring it moved. Those look identical in a graph.
The area postrema sits outside the blood-brain barrier and is where a great deal of the nausea signalling in this class originates. That is why the effect is central and not gastric irritation.
The rule of thumb is fine; the edge cases are where it earns its keep.
Read the full topic (91 posts)
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