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ForumsTirzepatide (Mounjaro / Zepbound)GIP receptor: the underappreciated half of tirzepatide's mechanism — need advice Page 3

GIP receptor: the underappreciated half of tirzepatide's mechanism — need advice

Dr.EM_Chicago Tue, Nov 4, 2025 at 7:40 AM 15 replies 1,283 viewsPage 3 of 3
Dr.PathRoch
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Nov 5, 2025 at 12:34 PM#11
Dr.Martinez 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.

Thank you — that is the clearest version of this I have read, and I have read a lot of them. Sending this to two other people who asked me the same thing last week.

20 20MikeFit_NJ, InsuranceTom, WendyG_ATL and 17 others
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GenomicsKate
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Nov 6, 2025 at 10:24 AM#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.

19 19KristenIndy, MarkLI_maint, Dr.PeteFamMed and 16 others
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PharmD_Rodriguez
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Nov 7, 2025 at 8:14 AM#13
james_edin said:
The mechanism is more central than most summaries suggest.

Pushing back on james_edin here. I would resist the confidence. Half of what this board was certain about two years ago has since been quietly dropped, and nobody went back to correct the threads.

18 18robert_kc, dan_philly, MeganSA_TX and 15 others
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VendorMark
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Nov 8, 2025 at 6:05 AM#14

Adding the numbers, since they settle part of this. If you are going to change something, change one thing and give it long enough to express itself. Four weeks is the usual minimum for anything pharmacological on this board, and two weeks of data has told you almost nothing.

17 17Dr.PeteFamMed, claudia_zurich, nancy_portland and 14 others
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Admin
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Nov 9, 2025 at 3:56 AM#15

Moderator note: two posts asking for a source have been merged into one. Please search the thread before asking again. Tagging this one for the weekly digest.

Last edited: Nov 9, 2025 at 7:56 AM
16 16PeptideSynthNJ, Dr.KarenChen, Dr.NateNeph and 13 others
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