GLP-1/GIP receptor co-agonism — my results so far

PeptideChemSF said:

The GIP arm is doing real work rather than padding the label.

Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. 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.

The figures, for anyone assembling their own picture. 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.

Dr.ObesityMed said:

The "tirzepatide is simply better" summary irritates me.

Adding the part of the answer the thread has not reached. 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.

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?

Closing the loop on my own question.

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.