alex_tucson said:

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

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.

Following on from traveltech_sara — and this may be the naive question:

How much of the tirzepatide advantage is the GIP component and how much is simply that the dose ladder goes higher in receptor-occupancy terms?

HPLC_Greg said:

Dose-response modeling for tirzepatide: Emax model fitting to the STEP/SURMOUNT dose-finding data shows: Semaglutide: ED50 ≈ 0.6mg, Emax ≈ -18%, Hill…

Adding the part of the answer the thread has not reached. The useful move here is to separate what is established from what is widely repeated. Those two sets overlap less than the confident tone of most write-ups suggests, and the second set is where nearly all the disagreement on this board comes from.

Reporting back.

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

rachel_ABQ said:

The useful move here is to separate what is established from what is widely repeated.

True, though the ladder is longer and that is not a neutral detail — six dose steps means six opportunities to stall on the way up, and plenty of people never reach the dose the headline number came from.