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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

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

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

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. Numbers rather than impressions, if you have them.

— SleepFixSam · corrections welcome and will be edited into this post with credit
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FDA_TrackerJim
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Mar 7, 2024 at 6:46 AM#2
SleepFixSam said:
Four weeks is the pharmacokinetics, not caution.

No disagreement with SleepFixSam. One condition attached. 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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Dr.NutriCornell
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Mar 7, 2024 at 7:13 AM#3
SleepFixSam 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.

Ask again with the specifics and you will get a better answer than this one.

Last edited: Mar 7, 2024 at 9:13 AM
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Dr.GutHealth
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Mar 7, 2024 at 7:40 AM#4

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

Ask again with the specifics and you will get a better answer than this one.

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greg_boulder
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Mar 7, 2024 at 10:05 AM#5
FDA_TrackerJim 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…

Mine went the same way, slower.

Last edited: Mar 7, 2024 at 12:05 PM
1 21ben_calgary
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