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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

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

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 actually want to know 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. If the honest answer is that nobody knows, that is a useful answer and I would rather have it.

— 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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Dr.RenalNash
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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…

Agreeing with rick_sfbay, 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.

Last edited: Sep 2, 2025 at 9:09 AM
20 15pam_stl, wei_SG, cory_ATX and 17 others
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Dr.CardioMD
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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 14tony_orlando, Dr.NephBHM_UK, kim_atl_prep and 16 others
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PharmHunterJen
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Sep 2, 2025 at 4:21 AM#4

Taking the question as asked, rather than the general version of it. 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.

18 13Dr.PainCLE, mike_mealprep, NicoleRaleigh and 15 others
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MaxMetOK
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Sep 2, 2025 at 4:50 AM#5
Dr.RenalNash said:
Four weeks is the pharmacokinetics, not caution.

This matches mine closely enough to be worth saying so out loud.

Last edited: Sep 2, 2025 at 9:50 AM
17 12PurityPaulOR, MaxMetOK, MounjBrad and 14 others
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