This gets cited here weekly, usually second-hand, so it is worth setting out what it does and does not establish.
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 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.
What would genuinely help is knowing 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.
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.
DerekSJ_a1c said:The dose-response is real but shallow at the top.
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.
DerekSJ_a1c 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.
Ask again with the specifics and you will get a better answer than this one.
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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.
TirzTom said:Agreed, though "tolerable" needs defining.
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.