Tirzepatide half-life and injection timing — PK data

Dr.PulmRoch said:

SURMOUNT-1 landed around 20.9% mean weight loss at 15mg over 72 weeks, against roughly 15% for semaglutide 2.4mg in STEP 1.

Saving this. It is the first explanation that did not require me to already understand it.

From the other side of the consultation, briefly.

Dose-response modeling for tirzepatide: Emax model fitting to the STEP/SURMOUNT dose-finding data shows:

Semaglutide: ED50 ≈ 0.6mg, Emax ≈ -18%, Hill coefficient ≈ 1.3
Tirzepatide: ED50 ≈ 6mg, Emax ≈ -25%, Hill coefficient ≈ 1.5

Clinical implication: most patients achieve >80% of maximal response by the mid-range dose (1.7mg sema, 10mg tirz). Going to the maximum dose provides diminishing returns — possibly not worth the additional side effect burden for some patients. Individualize dosing based on response vs tolerability.

jim_asheville said:

The pharmacokinetics explain nearly every practical question asked here.

This is where I part company with the consensus forming above. Pushing back on the anecdote-stacking. Twenty people reporting the same thing is twenty samples from the same self-selected pool, not twenty independent confirmations.

The figures, for anyone assembling their own picture. If you are going to change something, change one thing and give it long enough to express itself. Four weeks is the usual minimum for anything pharmacological on this board, and two weeks of data has told you almost nothing.

Correct me if the detail matters more than I have assumed.

Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful. Tagging this one for the weekly digest.