Adding the numbers, since they settle part of this. For anyone assembling their own picture: Tmax is one to three days, terminal half-life about 165 to 170 hours, steady state at four to five weeks, and subcutaneous bioavailability near 89%. Those four numbers explain most of the questions people ask about timing.
One thing that is still open after CarlaRPh_TPA’s answer:
What the dose-response curve actually looks like above 1.7mg, because the trial means hide how few people account for the extra loss?
anders_CPH said:For anyone assembling their own picture: Tmax is one to three days, terminal half-life about 165 to 170 hours, steady state at four to five weeks, and…
There is a second half to this that has not been said yet. The mechanism that matters here is not stomach emptying, it is central. GLP-1 receptor agonism in the arcuate nucleus stimulates POMC neurons and suppresses AgRP/NPY signalling, which is why the effect is appetite and food salience rather than physical fullness. Delayed gastric emptying largely tachyphylaxes over the first months; the appetite effect does not.
I would rather be corrected than agreed with, if it comes to it.
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Browse GL BiochemClosing the loop on my own question.
Following this thread I went back and re-read the extension data properly. The point about trough rather than peak explains the pattern I was seeing on day six, which I had been blaming on the vial.
DebRD_ATL said:The mechanism that matters here is not stomach emptying, it is central.
DebRD_ATL has the substance of this right. The condition it depends on is worth stating. Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak. People who dose late are not losing a peak, they are letting the trough fall, and the appetite effect tracks the trough.