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.
Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak. People who dose late are not losing a peak, they are letting the trough fall, and the appetite effect tracks the trough.
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 would genuinely help is knowing how much of the between-person variation is pharmacokinetic and how much is just adherence measured badly. Happy to be told the question itself is wrong.
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.
Dr.MetabolicMD said:Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.
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.
Dr.MetabolicMD said:Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.
Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. 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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Browse GL BiochemShort answer first, then the reasoning. 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".
julia.endo 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.
If somebody has the primary source to hand I would rather cite it than paraphrase it.