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Evidence-based GLP-1 & peptide discussion since 2023
ForumsDosing & ProtocolsPK/PD modeling for tirzepatide — looking for input Page 3

PK/PD modeling for tirzepatide — looking for input

Dr.EndoIndy Tue, Jun 25, 2024 at 7:43 PM 15 replies 1,918 viewsPage 3 of 3
hank_denver
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Denver, CO
Jun 26, 2024 at 2:02 PM#11
sophie_paris said:
SURMOUNT-1 landed around 20.9% mean weight loss at 15mg over 72 weeks, against roughly 15% for semaglutide 2.4mg in STEP 1.

That reframing is the part I needed.

32 5ingrid_STO, pete_nash, hank_denver and 29 others
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rachel_ABQ
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Albuquerque, NM
Jun 26, 2024 at 5:29 PM#12

From the other side of the consultation, briefly.

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.

33 6DadBodDave, AmyNC_wife, SkepticalSean and 30 others
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Dr.BariatricHTX
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Jun 26, 2024 at 8:56 PM#13
pat_auckland said:
The pharmacokinetics explain nearly every practical question asked here.

Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. I think the framing smuggles in the conclusion. Ask it the other way round and the obvious answer reverses, which usually means the question is doing the work.

34 7Dr.EM_Chicago, pete_RVA, CarlaRPh_TPA and 31 others
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Dr.AddMedPHL
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Jun 27, 2024 at 12:23 AM#14

Adding the numbers, since they settle part of this. For anyone reading later: the numbers in this thread are worth checking against a primary source before you act on them, including mine. Half the figures circulating in this community trace back to a secondary summary that dropped a qualifier.

35 8TomFromTexas, mike.trainer_LA, sarah_nash92 and 32 others
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mike_mod
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Jun 27, 2024 at 3:50 AM#15

Moderator note: the sourcing question belongs in the vendor section and has been split out.

36 9PurityPaulOR, MaxMetOK, MounjBrad and 33 others
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