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.
What I actually want to know 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.
I have searched first, so if this is covered somewhere point me at it and I will read it.
Dr.AddMedPHL said:The dose-response is real but shallow at the top.
Dr.AddMedPHL has the substance of this right. The condition it depends on is worth stating. 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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View Resultsgreg_boulder 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…
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.
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.