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Evidence-based GLP-1 & peptide discussion since 2023
ForumsTirzepatide (Mounjaro / Zepbound)5mg → 10mg → 15mg titration — looking for input

5mg → 10mg → 15mg titration — looking for input

MikeKY_noInsulin Thu, Mar 21, 2024 at 9:19 PM 30 replies 2,350 viewsPage 1 of 6
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MikeKY_noInsulin
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Oct 2024
Louisville, KY
Mar 21, 2024 at 9:19 PM#1

Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.

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.

What I am after 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. Happy to be told the question itself is wrong.

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.
38 8sean_dublin, hannah_MT, Dr.SportsMedIN and 35 others
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DanielChem_CHI
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Mar 21, 2024 at 9:36 PM#2
MikeKY_noInsulin 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…

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

37 7Dr.DermMIA, fiona_VT, denise_HTX and 34 others
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NurseKim_ATL
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Mar 21, 2024 at 9:53 PM#3
MikeKY_noInsulin 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.

36 6ingrid_STO, pete_nash, hank_denver and 33 others
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DeniseRN_TPA
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Mar 21, 2024 at 10:10 PM#4

This one has a reasonably settled answer, so here it is. 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 22, 2024 at 1:10 AM
35 5LindaRN_retired, tommy_boulder, hyun_seoul and 32 others
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KetoKyle
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Mar 21, 2024 at 11:42 PM#5
DanielChem_CHI 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 matches mine closely enough to be worth saying so out loud. Posting only so the count is not one.

34 4JakeBK_lifts, DerekSJ_a1c, paige_pharma and 31 others
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