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ForumsDosing & ProtocolsDo you inject morning or night? Does it matter? — looking for input

Do you inject morning or night? Does it matter? — looking for input

TomTeleRx Sun, Dec 28, 2025 at 6:24 PM 8 replies 986 viewsPage 1 of 2
TomTeleRx
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Dec 28, 2025 at 6:24 PM#1

Writing this once so I can stop repeating it across threads. 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

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.

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

So the question, as narrowly as I can put it: why the interval is four weeks rather than two, and whether a slower ladder gets to the same place. Happy to be told the question itself is wrong.

— TomTeleRx · corrections welcome and will be edited into this post with credit
21 16pete_manc_UK, anna.melb_AU, mark_tokyo and 18 others
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Dr.NateNeph
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Dec 28, 2025 at 6:59 PM#2
TomTeleRx said:
Four weeks is the pharmacokinetics, not caution.

That is correct as far as it goes, and here is where it stops going. 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.

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MikeFit_NJ
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Dec 28, 2025 at 7:34 PM#3
TomTeleRx said:
Four weeks is the pharmacokinetics, not caution.

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.

Last edited: Dec 28, 2025 at 10:34 PM
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Dr.DermMIA
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Dec 28, 2025 at 8:09 PM#4

Answering the narrow version, because the broad one does not have a single answer. 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.

Last edited: Dec 28, 2025 at 10:09 PM
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PharmHunterJen
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Dec 28, 2025 at 11:23 PM#5
Dr.NateNeph 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…

This is my experience too, for whatever a second data point is worth.

Last edited: Dec 29, 2025 at 5:23 AM
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