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 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.
The question I want answered is what the dose-response curve actually looks like above 1.7mg, because the trial means hide how few people account for the extra loss. I would rather have one careful answer than five confident ones.
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
MASHdoc_SA said:Steady state is the thing most people miss.
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.
MASHdoc_SA said:Steady state is the thing most people miss.
I read this differently from MASHdoc_SA, 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.
Ask again with the specifics and you will get a better answer than this one.
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Shop Reference StandardsShort answer first, then the reasoning. 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.
Dr.SurgeonPGH said:All true, with one condition: that curve is for people who reached the dose on schedule.
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.