GIP receptor pharmacology — my results so far

SarahChen_PharmD said:

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

Pushing back on SarahChen_PharmD 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.

One concrete data point for the thread. 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.CardioMD said:

The "tirzepatide is simply better" summary irritates me.

There is a second half to this that has not been said yet. 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.

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

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

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

Closing the loop on my own question.

Update: the eight-week restart pattern people described is exactly what happened. I nearly abandoned it at week five.