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ForumsPharmacology & MechanismsGIP receptor pharmacology — what worked for you?

GIP receptor pharmacology — what worked for you?

Dr.AddMedPHL Sat, Nov 23, 2024 at 8:17 PM 19 replies 1,906 viewsPage 1 of 4
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Dr.AddMedPHL
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Nov 23, 2024 at 8:17 PM#1

I moved from semaglutide to tirzepatide after a long stall and the first eight weeks looked like starting over — which I gather is the usual pattern rather than a lucky one.

The question I want answered is whether anyone has held 10mg long term rather than climbing, and what happened over the following year.

Happy to be told the question itself is wrong.

14 9FitDadDave, RunnerRach, TrialNerd_Beth and 11 others
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DataDave
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Nov 23, 2024 at 8:22 PM#2

Short answer first, then the reasoning. 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. That matters when you are deciding whether a dose step has finished expressing itself.

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traveltech_sara
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Nov 23, 2024 at 10:52 PM#3
DataDave 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.

True, though the ladder is longer and that is not a neutral detail — six dose steps means six opportunities to stall on the way up, and plenty of people never reach the dose the headline number came from.

Last edited: Nov 24, 2024 at 1:52 AM
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claudia_zurich
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Nov 24, 2024 at 1:22 AM#4
Dr.AddMedPHL said:
I moved from semaglutide to tirzepatide after a long stall and the first eight weeks looked like starting over — which I gather is the usual pattern…

This matches mine closely enough to be worth saying so. SURMOUNT-1 landed around 20.9% mean weight loss at 15mg over 72 weeks, against roughly 15% for semaglutide 2.4mg in STEP 1. Different trials, different populations, so the comparison is indicative rather than decisive — but SURPASS-2 was a genuine head-to-head and it pointed the same way.

Last edited: Nov 24, 2024 at 7:22 AM
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PeptideChemSF
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Nov 24, 2024 at 4:21 PM#5

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.

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