Collecting this in one place because it comes up every few weeks and the answer is always assembled from scratch. It is about semaglutide, and it is deliberately narrow — everything I am not confident about is marked as such.
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".
That holds for the injectable. The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people quote them as if they were.
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.
What I am after is how much of the between-person variation is pharmacokinetic and how much is just adherence measured badly. Numbers rather than impressions, if you have them.
BethLabQueen said:The dose-response is real but shallow at the top.
Agreed, though "tolerable" needs defining. A dose you tolerate by eating almost nothing is not tolerated, it is being paid for somewhere else — usually in lean mass, sometimes in adherence three months later.
BethLabQueen said:The dose-response is real but shallow at the top.
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.
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Browse GL BiochemThis one has a reasonably settled answer, so here it is. Steady state is the thing most people miss. The terminal half-life is about a week, so every dose step takes four to five weeks to fully express itself. Judging a step at day ten is judging the ascent, not the plateau, and it is the single commonest reason people escalate before they needed to.
MikeFit_NJ said:Agreed, though "tolerable" needs defining.
All true, with one condition: that curve is for people who reached the dose on schedule. Anyone who slowed the ladder for tolerability is on a different, flatter curve, and comparing yourself with the published mean will make you feel like a non-responder when you are not.