GIP receptor pharmacology — January 2024

anders_CPH said:

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

This is where I part company with the consensus forming above. 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.

Worth separating that from the pharmacology, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.

Dr.MetabolicMD said:

The "tirzepatide is simply better" summary irritates me.

Coming at Dr.MetabolicMD’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.

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

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

Reporting back.

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.