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.
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.
If the honest answer is that nobody knows, that is a useful answer and I would rather have it.
Short answer first, then the reasoning. Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak. People who dose late are not losing a peak, they are letting the trough fall, and the appetite effect tracks the trough.
InsuranceTom said:Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.
No disagreement with InsuranceTom. One condition attached. 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".
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View ResultsDoseLogDan 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…
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.
Clinical perspective, offered as context rather than as advice.
DoseLogDan 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.