Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.
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 follow-up is short relative to how long people actually take these drugs, so durability is an assumption here rather than a finding.
What I actually want to know 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.
JakeBK_lifts said:The dose-response is real but shallow at the top.
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.
Happy to go further on any of that.
JakeBK_lifts 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 ResultsTaking the question as asked, rather than the general version of it. 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.
Happy to go further on any of that.
PharmacoVig_BOS 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.