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Evidence-based GLP-1 & peptide discussion since 2023
ForumsDosing & ProtocolsTirzepatide titration: 2.5→5→7.5→10→12.5→15mg guide Page 3

Tirzepatide titration: 2.5→5→7.5→10→12.5→15mg guide

Dr.Martinez Mon, Feb 19, 2024 at 5:20 PM 181 replies 34,127 viewsPage 3 of 20
mel_PDX
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Feb 22, 2024 at 12:45 PM#11
chris_chi24 said:
Steady state is faster than people expect: half-life about five days, so you are at plateau in roughly three to four weeks rather than five.

Saving this. It is the first explanation that did not require me to already understand it. Sending this to two other people who asked me the same thing last week.

39 14Dr.NateNeph, PharmD_Rodriguez, julia.endo and 36 others
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SarahChen_PharmD
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Feb 23, 2024 at 2:43 AM#12

Clinical perspective, offered as context rather than as advice.

Dose-response modeling for tirzepatide: Emax model fitting to the STEP/SURMOUNT dose-finding data shows:

Semaglutide: ED50 ≈ 0.6mg, Emax ≈ -18%, Hill coefficient ≈ 1.3
Tirzepatide: ED50 ≈ 6mg, Emax ≈ -25%, Hill coefficient ≈ 1.5

Clinical implication: most patients achieve >80% of maximal response by the mid-range dose (1.7mg sema, 10mg tirz). Going to the maximum dose provides diminishing returns — possibly not worth the additional side effect burden for some patients. Individualize dosing based on response vs tolerability.

Last edited: Feb 23, 2024 at 5:43 AM
38 13NurseKim_ATL, paul_denver, TinaHashiRN and 35 others
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pete_manc_UK
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Feb 23, 2024 at 4:41 PM#13
Dr.PathRoch said:
The GIP arm is doing real work rather than padding the label.

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.

Last edited: Feb 23, 2024 at 10:41 PM
37 12FitDadDave, RunnerRach, TrialNerd_Beth and 34 others
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TirzTom
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Feb 24, 2024 at 6:38 AM#14

The figures, for anyone assembling their own picture. 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.

36 11SandraNC_45, Dr.EndoIndy, tom_AK and 33 others
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Admin
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Feb 24, 2024 at 8:35 PM#15

Moderator note: leaving this open. It is being argued well and the disagreement is the useful part.

35 10PeptideSynthNJ, Dr.KarenChen, Dr.NateNeph and 32 others
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