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.
The question I want answered is how much of the between-person variation is pharmacokinetic and how much is just adherence measured badly. I have searched first, so if this is covered somewhere point me at it and I will read it.
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.
hyun_seoul said:Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.
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.
Correct me if the detail matters more than I have assumed.
hyun_seoul said:Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.
Pushing back on hyun_seoul here. 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".
PharmD_Rodriguez 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.