Collecting this in one place because it comes up every few weeks and the answer is always assembled from scratch. 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
One condition: holding indefinitely at a dose that is not doing anything is not patience, it is a stall with a nice name. The distinction is whether appetite has changed at all at the current step.
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 question I want answered is why the interval is four weeks rather than two, and whether a slower ladder gets to the same place. Not looking for reassurance. Looking for the part I have got wrong.
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…
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.
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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Browse GL BiochemShort answer first, then the reasoning. 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.
RetaRick_CA 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.