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ForumsDosing & ProtocolsWhen to hold at a dose vs continue titrating — looking for input

When to hold at a dose vs continue titrating — looking for input

rick_sfbay Tue, Sep 2, 2025 at 4:03 AM 13 replies 1,233 viewsPage 1 of 3
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rick_sfbay
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Sep 2, 2025 at 4:03 AM#1

A reference post rather than a discussion. Corrections are the point; I would rather this be right than mine. 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

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.

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

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. Not looking for reassurance. Looking for the part I have got wrong.

— rick_sfbay · corrections welcome and will be edited into this post with credit
21 16mike_mealprep, NicoleRaleigh, james_edin and 18 others
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BariatricNurseD
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Sep 2, 2025 at 4:09 AM#2
rick_sfbay 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…

No disagreement with rick_sfbay. One condition attached. 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.

Last edited: Sep 2, 2025 at 9:09 AM
20 15roxy_nash, tony_orlando, Dr.NephBHM_UK and 17 others
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MikeFit_NJ
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Sep 2, 2025 at 4:15 AM#3
rick_sfbay 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.

19 14DeniseRN_TPA, SandraNC_45, Dr.EndoIndy and 16 others
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Dr.SurgeonPGH
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Sep 2, 2025 at 4:21 AM#4

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.

Last edited: Sep 2, 2025 at 7:21 AM
18 13RickReta_CO, PharmHunterJen, TomTeleRx and 15 others
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SleepDoc_PDX
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Sep 2, 2025 at 4:50 AM#5
BariatricNurseD said:
Four weeks is the pharmacokinetics, not caution.

Can confirm. Same sequence, different timescale. Nothing to add that would improve it.

17 12mel_PDX, Dr.AddMedPHL, newstart_MO and 14 others
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