Micro-dosing semaglutide — 12 month update

TrialNerd_Beth said:

The mechanism that matters here is not stomach emptying, it is central.

I read this differently from TrialNerd_Beth, on substance rather than tone. Halving the dose and calling it splitting is not the same intervention, and this thread keeps mixing them. One changes the schedule; the other changes the exposure.

I would rather be corrected than agreed with, if it comes to it.

The figures, for anyone assembling their own picture. 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.

RetaRick_CA said:

Halving the dose and calling it splitting is not the same intervention, and this thread keeps mixing them.

There is a second half to this that has not been said yet. The dose-response is real but shallow at the top. Across STEP 1 and STEP 4 the gap between 1.7mg and 2.4mg is a couple of percentage points of body weight on average, and the average is carrying a wide spread — plenty of people at 1.7mg sit above the 2.4mg mean. If a dose is working and tolerable, "working" is the relevant variable, not "maximal".

One thing that is still open after amsterdam_pete’s answer:

How much of the between-person variation is pharmacokinetic and how much is just adherence measured badly?

Reporting back.

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.