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.
What I actually want to know 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.
MikeKY_noInsulin said:Four weeks is the pharmacokinetics, not caution.
MikeKY_noInsulin has the substance of this right. The condition it depends on is worth stating. 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.
MikeKY_noInsulin 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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View ResultsTaking the question as asked, rather than the general version of it. 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.
Dr.ObesityMed 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…
Same pattern here, and in the same order. Nothing to add that would improve it.