This one has a reasonably settled answer, so here it is. 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".
Six months in at 2.4mg. The first four months were close to the trial curve and the last two have been flat, which is roughly what the STEP 1 figure predicts if you read the tail rather than the headline.
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.
The question I want answered is 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.
HPLC_Greg said:The dose-response is real but shallow at the top.
Agreeing with HPLC_Greg, and the qualification matters more than the agreement. 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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Browse GL BiochemDr.EM_Chicago said:The first four months were close to the trial curve and the last two have been flat, which is roughly what the STEP 1 figure predicts if you read the…
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.
Adding the clinical framing, because it changes how the question reads.
Dr.EM_Chicago 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.