Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using 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.
Where I think it is weakest: the follow-up is short relative to how long people actually take these drugs, so durability is an assumption here rather than a finding.
What would genuinely help is knowing 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.
ben_calgary said:The mechanism that matters here is not stomach emptying, it is central.
That holds for the injectable. The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people quote them as if they were.
That is the short version; the long version is somebody else's post.
ben_calgary said:The mechanism that matters here is not stomach emptying, it is central.
I read this differently from ben_calgary, on substance rather than tone. The trial means are being read too generously in this thread. STEP populations were selected, supported, and titrated by protocol, and the real-world curves are consistently a few points worse. That difference is not noise, it is what happens when you remove the study infrastructure.
If somebody has the primary source to hand I would rather cite it than paraphrase it.
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Browse GL BiochemShort 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.
Dr.SurgeonPGH said:The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people…
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.