Taking the question as asked, rather than the general version of it. 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.
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.
For anyone assembling their own picture: Tmax is one to three days, terminal half-life about 165 to 170 hours, steady state at four to five weeks, and subcutaneous bioavailability near 89%. Those four numbers explain most of the questions people ask about timing.
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.
Happy to be told the question itself is wrong.
julia.endo said:The mechanism that matters here is not stomach emptying, it is central.
No disagreement with julia.endo. One condition attached. 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.
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View Resultsmia_MS2 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…
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.
Correct me if the detail matters more than I have assumed.
From the other side of the consultation, briefly.
mia_MS2 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.