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ForumsDosing & ProtocolsInjection technique: subcutaneous depot formation and absorption — my results so far

Injection technique: subcutaneous depot formation and absorption — my results so far

FitDadDave Tue, Feb 11, 2025 at 11:36 AM 14 replies 1,830 viewsPage 1 of 3
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FitDadDave
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Feb 11, 2025 at 11:36 AM#1

I titrated faster than the label because I felt fine, hit a wall at the third step, and had to come back down — which I now think was the predictable outcome rather than bad luck.

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.

The question I want answered 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.

43 13Dr.NephBHM_UK, kim_atl_prep, sarah_TO and 40 others
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Dr.NutriCornell
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Feb 11, 2025 at 11:44 AM#2

This one has a reasonably settled answer, so here it is. 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.

That is the short version; the long version is somebody else's post.

42 12Dr.SleepRoch, laura_annarbor, JenMemphis and 39 others
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SarahChen_PharmD
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Feb 11, 2025 at 11:52 AM#3
Dr.NutriCornell 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 right for the weekly injectables. For the daily agents the interval logic is different and the four-week convention does not transfer.

Last edited: Feb 11, 2025 at 2:52 PM
41 11paul_denver, TinaHashiRN, robert_kc and 38 others
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dave_SLC
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Feb 11, 2025 at 12:00 PM#4
FitDadDave said:
I titrated faster than the label because I felt fine, hit a wall at the third step, and had to come back down — which I now think was the predictable…

Same position here, arrived at the long way round. 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.

40 10FranDenver, Dr.BariatricHTX, LindaRN_retired and 37 others
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Dr.Martinez
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Feb 11, 2025 at 12:40 PM#5

Clinical perspective, offered as context rather than as advice.

PSA for titration users considering the 0.25mg starting dose: this dose is NOT intended for weight loss. It's a titration dose to let your body adjust. Don't be discouraged if you don't lose much in the first month.

The therapeutic dose for weight management starts at 1.7mg (semaglutide) or 5mg (tirzepatide). Be patient with the ramp-up.

39 9adam_van, Dr.SurgeonPGH, rachel_ABQ and 36 others
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