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ForumsPharmacology & MechanismsGLP-1/GIP receptor co-agonism — anyone have experience? Page 2

GLP-1/GIP receptor co-agonism — anyone have experience?

Dr.NephBHM_UK Thu, Apr 2, 2026 at 2:36 AM 36 replies 1,378 viewsPage 2 of 8
Dr.ObesityMed
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Apr 2, 2026 at 7:25 AM#6
anders_CPH 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.

Pushing back on anders_CPH here. The "tirzepatide is simply better" summary irritates me. It is better on mean weight loss, and the cardiovascular outcome evidence is far thinner than semaglutide's. If the reason for treating is cardiovascular risk rather than weight, the evidence base points the other way.

48 18EndoResFellow, PharmacoVig_BOS, SurmountFan_IN and 45 others
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josh_phd_bmore
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Apr 2, 2026 at 9:18 AM#7

Adding the numbers, since they settle part of this. Numbers worth memorising for this class: Tmax one to three days for the weekly peptides, terminal half-life about a week for semaglutide and about five days for tirzepatide, steady state at four to five half-lives, subcutaneous bioavailability high enough that site choice is irrelevant.

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PedsEndoPhilly
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Apr 2, 2026 at 11:11 AM#8
Dr.ObesityMed said:
The "tirzepatide is simply better" summary irritates me.

Coming at Dr.ObesityMed’s question from a different direction. The pharmacokinetics explain nearly every practical question asked here. Albumin binding above 99% slows clearance enough to make weekly dosing possible; a terminal half-life near a week means four to five weeks to steady state and therefore a four-week titration interval; subcutaneous bioavailability around 89% means injection site barely matters. Those three facts answer most timing questions before they are asked.

Correct me if the detail matters more than I have assumed.

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emma_london
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Apr 2, 2026 at 1:04 PM#9

One thing that is still open after claudia_zurich’s answer:

How much of the tirzepatide advantage is the GIP component and how much is simply that the dose ladder goes higher in receptor-occupancy terms?

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Dr.NephBHM_UK
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Apr 2, 2026 at 10:04 PM#10

Closing the loop on my own question.

Reporting back after another eight months at the same dose. Still losing slowly, no new side effects, and no reason I can find to climb further.

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