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Evidence-based GLP-1 & peptide discussion since 2023
ForumsPharmacology & MechanismsGLP-1/GIP receptor co-agonism — what worked for you? Page 2

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 2 of 3
DataDave
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May 17, 2025 at 10:09 AM#6
MikeFit_NJ said:
The GIP arm is doing real work rather than padding the label.

Pushing back on MikeFit_NJ 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.

39 9VendorMark, COA_Karl, MikeFit_NJ and 36 others
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wendy_avl
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May 17, 2025 at 10:01 PM#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.

38 8DoseLogDan, SleepFixSam, PurityPaulOR and 35 others
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EndoResFellow
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May 18, 2025 at 9:53 AM#8
DataDave said:
The "tirzepatide is simply better" summary irritates me.

Coming at DataDave’s question from a different direction. The mechanism is more central than most summaries suggest. Receptor agonism in the arcuate nucleus activates POMC neurons and inhibits AgRP/NPY signalling, and the downstream MC4R pathway is the same one disrupted in monogenic obesity — convergent genetic evidence that the target is the right one. Peripherally there is glucose-dependent insulin secretion, glucagon suppression and delayed gastric emptying, but the gastric component largely adapts over months while the central effect persists, which is why the durable effect is appetite rather than fullness.

37 7paul_denver, TinaHashiRN, robert_kc and 34 others
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BrianDallas92
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May 18, 2025 at 9:46 PM#9

A narrower follow-up, since the general answer is now clear:

Whether anyone has held 10mg long term rather than climbing, and what happened over the following year?

Last edited: May 18, 2025 at 10:46 PM
36 6Dr.EndoEP, GraceAZ_72, carl_compliance and 33 others
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zoe_NC
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May 21, 2025 at 6:48 AM#10

Reporting back.

I stayed at 10mg. Another six months, another 7kg, no new side effects, and my reading of the dose-response says the last two steps were never going to be worth what they cost me.

Last edited: May 21, 2025 at 7:48 AM
38 11mike_mealprep, NicoleRaleigh, james_edin and 35 others
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