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 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 I am trying to establish is how much of the between-person variation is pharmacokinetic and how much is just adherence measured badly. Practical detail welcome, however dull — the duller the better.
A1cHero_PHX 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.
A1cHero_PHX said:Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.
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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Browse GL BiochemThis one has a reasonably settled answer, so here it is. 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".
TirzTom 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.