Dr.Martinez 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…

Dr.Martinez has the substance of this right. The condition it depends on is worth stating. 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.

Happy to go further on any of that.

Dr.Martinez 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…

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.

Ask again with the specifics and you will get a better answer than this one.

This one has a reasonably settled answer, so here it is. 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.

PeptideChemSF said:

Four weeks is the pharmacokinetics, not caution.

Agreed, and subgroup analyses deserve particular suspicion. With enough subgroups something is significant by chance, and pre-registered subgroups are a different animal from ones found afterwards.

Correct me if the detail matters more than I have assumed.