Short answer first, then the reasoning. The GIP arm is doing real work rather than padding the label. GIP receptor agonism appears to improve adipose insulin sensitivity and lipid handling, and — counter-intuitively — GIP signalling in the CNS reduces nausea rather than adding to it, which is why tolerability at high total agonism is better than the GLP-1-only comparison would predict. SURPASS-2 is the cleanest head-to-head: tirzepatide beat semaglutide 1mg at every dose tier.

BenResearch_OR said:

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

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.

AussieAnna said:

I moved from semaglutide to tirzepatide after a long stall and the first eight weeks looked like starting over — which I gather is the usual pattern…

This matches mine closely enough to be worth saying so. Steady state is faster than people expect: half-life about five days, so you are at plateau in roughly three to four weeks rather than five. That matters when you are deciding whether a dose step has finished expressing itself.

Adding the clinical framing, because it changes how the question reads.

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.