Comparative pharmacokinetics: semaglutide vs tirzepatide vs retatrutide — need advice

JessicaH_TX said:

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

I will push back on the "any working dose is fine" framing. The maintenance evidence sits overwhelmingly at the top studied dose, and the extension data shows regain tracking dose reduction rather than tracking stopping. Holding low is reasonable; pretending it is evidentially equivalent is not.

One concrete data point for the thread. Worth knowing that the injection site changes very little. Abdomen, thigh and upper arm are bioequivalent for semaglutide, so a site change is not a plausible explanation for a bad week.

HPLC_Greg said:

I will push back on the "any working dose is fine" framing.

Adding the part of the answer the thread has not reached. Steady state is the thing most people miss. The terminal half-life is about a week, so every dose step takes four to five weeks to fully express itself. Judging a step at day ten is judging the ascent, not the plateau, and it is the single commonest reason people escalate before they needed to.

A narrower follow-up, since the general answer is now clear:

What the dose-response curve actually looks like above 1.7mg, because the trial means hide how few people account for the extra loss?

OP back with an update, since a thread like this is useless without one.

Update — tachyphylaxis to the gastric effect, persistence of the appetite effect. Two curves, and I had been watching the wrong one.