NurseAsh_DET said:

Maintenance phase reality on maintenance dosing: reached my goal 8 months ago and now I'm in maintenance.

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".

The figures, for anyone assembling their own picture. 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.

A narrower follow-up, since the general answer is now clear:

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

Dr.NateNeph said:

Worth knowing that the injection site changes very little.

I will push back on the "any working dose is fine" framing. The maintenance evidence sits overwhelmingly at the top studied dose, and the extension data shows regain tracking dose reduction rather than tracking stopping. Holding low is reasonable; pretending it is evidentially equivalent is not.

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

Dr.NateNeph said:

Worth knowing that the injection site changes very little.

The concept of "metabolic set point" and its relevance to maintenance dosing: the body actively defends a weight set point through hormonal feedback (leptin, ghrelin, insulin, GLP-1). After weight loss, these signals shift to promote weight regain[1].

GLP-1 agonists may work in part by resetting this set point — or at least overriding the counter-regulatory signals that drive regain. This would explain why continued treatment maintains weight loss while discontinuation leads to regain.

Understanding maintenance dosing through this lens reframes the drug from "weight loss tool" to "metabolic set point modulator."