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ForumsPharmacology & MechanismsGLP-1/GIP receptor co-agonism — what worked for you?

GLP-1/GIP receptor co-agonism — what worked for you?

zoe_NC Fri, May 16, 2025 at 4:25 AM 13 replies 1,641 viewsPage 1 of 3
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zoe_NC
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May 16, 2025 at 4:25 AM#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.

Numbers rather than impressions, if you have them.

44 14Dr.BariatricHTX, LindaRN_retired, tommy_boulder and 41 others
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Dr.GutHealth
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May 16, 2025 at 6:25 AM#2

This one has a reasonably settled answer, so here it is. 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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mike.trainer_LA
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May 16, 2025 at 8:25 AM#3
Dr.GutHealth 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.

Agreed on the mechanism, with the caveat that the head-to-head used semaglutide 1mg, not 2.4mg. It is still the best direct evidence available, but it is not the comparison most people think they are citing.

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Dr.PathRoch
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May 16, 2025 at 10:25 AM#4
zoe_NC 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…

Same position here, arrived at the long way round. 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.

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andrew_nyc
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May 16, 2025 at 10:17 PM#5

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: May 17, 2025 at 3:17 AM
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