Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.
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.
Where I think it is weakest: the population was selected and supported in ways a real cohort is not, so I would read the effect size as a ceiling rather than an expectation.
What I am after 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. Happy to be told the question itself is 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: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.
MikeKY_noInsulin 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.
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View ResultsThis one has a reasonably settled answer, so here it is. 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.
DanielChem_CHI 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 matches mine closely enough to be worth saying so out loud. Posting only so the count is not one.