Read the primary source rather than the write-up and the two do not agree, so here is what is actually in 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.
Where I think it is weakest: the subgroup findings are the part I trust least — with enough subgroups something is always significant, and these were not all pre-registered.
What I am trying to establish is what the trials actually did with participants who could not tolerate a step, because that is the situation I am in and the protocol summaries skip it. Tell me what I have not thought of.
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.
traveltech_sara 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…
Agreeing with traveltech_sara, and the qualification matters more than the agreement. 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.
traveltech_sara 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.
If somebody has the primary source to hand I would rather cite it than paraphrase it.
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Shop Reference StandardsThis 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.
Dr.RenalNash said:Four weeks is the pharmacokinetics, not caution.
Same pattern here, and in the same order. Nothing to add that would improve it.