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.
What I am after is how much of the between-person variation is pharmacokinetic and how much is just adherence measured badly.
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. 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.
Ask again with the specifics and you will get a better answer than this one.
PharmD_Rodriguez said:The mechanism that matters here is not stomach emptying, it is central.
That is correct as far as it goes, and here is where it stops going. 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.
If somebody has the primary source to hand I would rather cite it than paraphrase it.
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Shop Reference StandardsMikeKY_noInsulin 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…
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.
From the other side of the consultation, briefly.
MikeKY_noInsulin 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.