kate.chem said:

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

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.

That is the short version; the long version is somebody else's post.

kate.chem said:

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

Pushing back on kate.chem here. 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.

This one has a reasonably settled answer, so here it is. The dose-response is real but shallow at the top. Across STEP 1 and STEP 4 the gap between 1.7mg and 2.4mg is a couple of percentage points of body weight on average, and the average is carrying a wide spread — plenty of people at 1.7mg sit above the 2.4mg mean. If a dose is working and tolerable, "working" is the relevant variable, not "maximal".

TirzTom said:

Agreed, though "tolerable" needs defining.

All true, with one condition: that curve is for people who reached the dose on schedule. Anyone who slowed the ladder for tolerability is on a different, flatter curve, and comparing yourself with the published mean will make you feel like a non-responder when you are not.