One concrete data point for the thread. Worth knowing that the injection site changes very little. Abdomen, thigh and upper arm are bioequivalent for semaglutide, so a site change is not a plausible explanation for a bad week.
One thing that is still open after DebRD_ATL’s answer:
How much of the between-person variation is pharmacokinetic and how much is just adherence measured badly?
PharmacoVig_BOS said:Worth knowing that the injection site changes very little.
Adding the part of the answer the thread has not reached. 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.
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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.
carl_compliance said:The mechanism that matters here is not stomach emptying, it is central.
Agreeing with carl_compliance, and the qualification matters more than the agreement. 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.