Semaglutide cardiovascular benefit: SELECT trial deep dive — looking for input

LarryQC_SD said:

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

This is where I part company with the consensus forming above. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.

Adding the numbers, since they settle part of this. 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.

Dr.LipidDallas said:

The "earlier than weight loss explains" argument is weaker than this thread makes it sound.

Adding the part of the answer the thread has not reached. 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".

Following on from mia_MS2 — and this may be the naive question:

Whether anyone has held at a sub-maximal dose long term and kept the result, or whether the maintenance data only exists at 2.4mg?

OP back with an update, since a thread like this is useless without one.

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.