Dr.PeteFamMed said:

The mechanism is more central than most summaries suggest.

Agreed, though "tolerable" needs defining. A dose you tolerate by eating almost nothing is not tolerated, it is being paid for somewhere else — usually in lean mass, sometimes in adherence three months later.

steph_laguna said:

Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.

Thank you — that is the clearest version of this I have read, and I have read a lot of them.

Dr.PeteFamMed said:

The mechanism is more central than most summaries suggest.

This is where I part company with the consensus forming above. The trial means are being read too generously in this thread. STEP populations were selected, supported, and titrated by protocol, and the real-world curves are consistently a few points worse. That difference is not noise, it is what happens when you remove the study infrastructure.

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.

Moderator note: reminder that nothing in this thread is medical advice, and that clinical claims need a source.