Answering the narrow version, because the broad one does not have a single answer. 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".
I have been on semaglutide for nine months, currently holding 1.7mg rather than pushing to 2.4mg, and the last two dose steps bought me much less than the first two did.
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.
So the question, as narrowly as I can put it: what the dose-response curve actually looks like above 1.7mg, because the trial means hide how few people account for the extra loss.
Practical detail welcome, however dull — the duller the better.
DanielChem_CHI said:The dose-response is real but shallow at the top.
That is correct as far as it goes, and here is where it stops going. 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.
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Shop Reference Standardsgreg_boulder said:I have been on semaglutide for nine months, currently holding 1.7mg rather than pushing to 2.4mg, and the last two dose steps bought me much less than…
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.
From the other side of the consultation, briefly.
greg_boulder said:...but the FDA says semaglutide...
Interesting point. I want to add some regulatory nuance: the FDA labeling reflects the specific clinical trial data submitted for approval. Real-world clinical practice often extends beyond the FDA label based on emerging evidence and clinical judgment.
Example: semaglutide was first approved for diabetes (Ozempic), then obesity (Wegovy). The molecule didn't change — our understanding of its applications expanded. Similarly, semaglutide may evolve as more data accumulates.