De-escalation protocols — looking for input

SandraNC_45 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…

That is correct as far as it goes, and here is where it stops going. 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.

SandraNC_45 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…

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.

Taking the question as asked, rather than the general version of 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.

Dr.ReproEndo said:

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…

This is my experience too, for whatever a second data point is worth. Nothing to add that would improve it.