This is the version of the explanation I wish somebody had given me, written down before I forget what confused me. It is about the titration schedule, and it is deliberately narrow — everything I am not confident about is marked as such.
What is actually established
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.
The condition it depends on
That is right for the weekly injectables. For the daily agents the interval logic is different and the four-week convention does not transfer.
The practical version
The arithmetic in one line: half-life about a week, so steady state at four to five weeks, so a four-week interval is one steady state per step. Two-week intervals mean every step is dosed onto a rising curve.
What I am not sure about
The bit I cannot resolve on my own 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. Numbers rather than impressions, if you have them.
JennaRN 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…
JennaRN has the substance of this right. The condition it depends on is worth stating. 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.
JennaRN 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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Shop Reference StandardsTaking 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.
FDA_TrackerJim 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…
Second this. Posting only so the count is not one.