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 dose-response is real but shallow at the top. Across STEP 1 and STEP 4 the gap between 1.7mg and 2.4mg is a couple of percentage points of body weight on average, and the average is carrying a wide spread — plenty of people at 1.7mg sit above the 2.4mg mean. If a dose is working and tolerable, "working" is the relevant variable, not "maximal".
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. If the honest answer is that nobody knows, that is a useful answer and I would rather have it.
NeuroNate said:The dose-response is real but shallow at the top.
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.
NeuroNate said:The dose-response is real but shallow at the top.
I will push back on the "any working dose is fine" framing. The maintenance evidence sits overwhelmingly at the top studied dose, and the extension data shows regain tracking dose reduction rather than tracking stopping. Holding low is reasonable; pretending it is evidentially equivalent is not.
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View ResultsShort answer first, then the reasoning. 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.
anders_CPH 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.