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 completion rate deserves as much attention as the headline, because a large effect among those who finished is a different claim from a large effect among those enrolled.
What would genuinely help is knowing what the dose-response curve actually looks like above 1.7mg, because the trial means hide how few people account for the extra loss. Numbers rather than impressions, if you have them.
TrialTracker_MD 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.
TrialTracker_MD said:The mechanism that matters here is not stomach emptying, it is central.
This is where I part company with the consensus forming above. 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.
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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.
NeuroNate 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.