Read the primary source rather than the write-up and the two do not agree, so here is what is actually in it.
Four weeks is the pharmacokinetics, not caution. With a one-week half-life you need four to five half-lives to reach steady state, so at two weeks you are dosing on top of a concentration that has not finished rising. Escalating then stacks exposure and you get the side-effect burden of the higher dose before you have seen the benefit of the current one.
Where I think it is weakest: the comparator does most of the work in how this gets reported, and it is not the comparator most people think they are citing.
The narrow version of the question is why the interval is four weeks rather than two, and whether a slower ladder gets to the same place. Not looking for reassurance. Looking for the part I have got 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.
NauseaFreeNow said:Four weeks is the pharmacokinetics, not caution.
Agreeing with NauseaFreeNow, and the qualification matters more than the agreement. Holding longer is the underrated move. A step that is uncomfortable at week two is frequently comfortable at week six with no change in dose, because the gastric-emptying component tachyphylaxes while the appetite effect persists. Escalating at week two throws that adaptation away.
That is the short version; the long version is somebody else's post.
NauseaFreeNow said:Four weeks is the pharmacokinetics, not caution.
I disagree that the ladder is purely tolerability. The maintenance and regain data cluster at the top doses, so a ladder abandoned halfway leaves you outside the evidence base for the part that matters most — keeping it off.
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Browse GL BiochemAnswering the narrow version, because the broad one does not have a single answer. The trials generally allowed a step to be held or reduced and then retried, and people who did that mostly arrived at the same place a few weeks later. The end point of the ladder is set by tolerability, not by a schedule, and there is no evidence that reaching the top faster produces a better outcome.
sarah.morrison said:A step that is uncomfortable at week two is frequently comfortable at week six with no change in dose, because the gastric-emptying component…
This is my experience too, for whatever a second data point is worth.