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ForumsDosing & ProtocolsHas anyone dealt with weekend vs weekday injection?

Has anyone dealt with weekend vs weekday injection?

mel_PDX Wed, Jul 2, 2025 at 4:53 PM 34 replies 1,505 viewsPage 1 of 7
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mel_PDX
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Jul 2, 2025 at 4:53 PM#1

This gets cited here weekly, usually second-hand, so it is worth setting out what it does and does not establish.

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.

Where I think it is weakest: the population was selected and supported in ways a real cohort is not, so I would read the effect size as a ceiling rather than an expectation.

The narrow version of the question 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.

Note on sourcing:
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
12 7Dr.NateNeph, PharmD_Rodriguez, julia.endo and 9 others
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amsterdam_pete
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Jul 2, 2025 at 6:10 PM#2
mel_PDX 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…

mel_PDX has the substance of this right. The condition it depends on is worth stating. 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.

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Dr.MetabolicMD
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Jul 2, 2025 at 7:27 PM#3
mel_PDX 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…

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.

10 5HealthEcon_DC, PedsEndoPhilly, SleepDoc_PDX and 7 others
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Dr.Martinez
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Jul 2, 2025 at 8:44 PM#4

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

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DeniseRN_TPA
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Jul 3, 2025 at 4:11 AM#5
amsterdam_pete 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…

This is my experience too, for whatever a second data point is worth. Nothing to add that would improve it.

Last edited: Jul 3, 2025 at 7:11 AM
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