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 am trying to establish 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.
This 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.
FDA_TrackerJim said:Steady state is the thing most people miss.
FDA_TrackerJim has the substance of this right. The condition it depends on is worth stating. The mechanism that matters here is not stomach emptying, it is central. GLP-1 receptor agonism in the arcuate nucleus stimulates POMC neurons and suppresses AgRP/NPY signalling, which is why the effect is appetite and food salience rather than physical fullness. Delayed gastric emptying largely tachyphylaxes over the first months; the appetite effect does not.
Correct me if the detail matters more than I have assumed.
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Browse GL BiochemMASHdoc_SA 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.
Clinical perspective, offered as context rather than as advice.
MASHdoc_SA 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.