This gets cited here weekly, usually second-hand, so it is worth setting out what it does and does not establish.
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.
Where I think it is weakest: the population was selected and supported in ways a real cohort is not, so I would read the effect size as a ceiling rather than an expectation.
The bit I cannot resolve on my own is how much of the between-person variation is pharmacokinetic and how much is just adherence measured badly. Numbers rather than impressions, if you have them.
Dr.GutHealth said:Steady state is the thing most people miss.
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.
Dr.GutHealth said:Steady state is the thing most people miss.
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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Shop Reference StandardsTaking 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.
If somebody has the primary source to hand I would rather cite it than paraphrase it.
labquiet_amy 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.