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Evidence-based GLP-1 & peptide discussion since 2023
ForumsDosing & ProtocolsBest time of day to inject? I keep forgetting at night — looking for input

Best time of day to inject? I keep forgetting at night — looking for input

SleepFixSam Thu, Mar 7, 2024 at 6:19 AM 12 replies 2,216 viewsPage 1 of 3
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SleepFixSam
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Mar 7, 2024 at 6:19 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

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

What I actually want to know is why the interval is four weeks rather than two, and whether a slower ladder gets to the same place. Practical detail welcome, however dull — the duller the better.

— SleepFixSam · corrections welcome and will be edited into this post with credit
5 0pete_nash, hank_denver, carlos_SATX and 2 others
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Dr.CardioMD
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Mar 7, 2024 at 6:46 AM#2
SleepFixSam 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…

That is correct as far as it goes, and here is where it stops going. 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: Mar 7, 2024 at 12:46 PM
4 24Dr.NephBHM_UK, kim_atl_prep, sarah_TO and 1 other
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NeuroNate
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Mar 7, 2024 at 7:13 AM#3
SleepFixSam 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.

3 23sarah_TO, wendy_avl, jason_paloalto
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newstart_MO
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Mar 7, 2024 at 7:40 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.

2 22TrialNerd_Beth, HPLC_Greg
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TinaHashiRN
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Mar 7, 2024 at 10:05 AM#5
Dr.CardioMD said:
Four weeks is the pharmacokinetics, not caution.

Adding a me-too, because a thread of one person's experience is not much use. Posting only so the count is not one.

1 21MikeNYC_runner
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