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ForumsPharmacology & MechanismsGIP receptor pharmacology — why GIP agonism enhances GLP-1 Page 3

GIP receptor pharmacology — why GIP agonism enhances GLP-1

NeuroNate Sun, Jun 7, 2026 at 1:36 PM 13 replies 219 viewsPage 3 of 3
AmyNC_wife
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Jun 7, 2026 at 8:54 PM#11
Dr.LeslieOBGYN 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.

Saving this. It is the first explanation that did not require me to already understand it.

27 0JessicaM_2024, TomFromTexas, mike.trainer_LA and 24 others
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jim_asheville
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Jun 8, 2026 at 3:00 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: Jun 8, 2026 at 6:00 AM
28 1BenResearch_OR, MikeKY_noInsulin, Dr.RaviCardio and 25 others
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Dr.GutHealth
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Jun 8, 2026 at 9:05 AM#13
rachel_ABQ said:
The mechanism is more central than most summaries suggest.

This is where I part company with the consensus forming above. Filing an objection on the n=1 problem. Personal experience is genuine evidence about one person and very weak evidence about anybody else, and this thread keeps promoting the first into the second.

Last edited: Jun 8, 2026 at 2:05 PM
29 2jennifer_SEA, tyler_CSCS, VanRx_Mike and 26 others
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raj_cambridge
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Jun 8, 2026 at 3:10 PM#14

Adding the numbers, since they settle part of this. The boring version of this is the one that works, and the boring version is: measure a baseline, change one variable, wait, measure again under the same conditions. Nobody wants that answer and it is still the answer.

30 3PharmHunterJen, TomTeleRx, DoseLogDan and 27 others
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mike_mod
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Jun 8, 2026 at 9:15 PM#15

Moderator note: leaving this open. It is being argued well and the disagreement is the useful part. Report rather than reply if it drifts again.

31 4PurityPaulOR, MaxMetOK, MounjBrad and 28 others
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