SURMOUNT-5: Tirzepatide vs semaglutide head-to-head — looking for input

NurseAsh_DET 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.

This answered a question I did not know how to ask. Printing the relevant bit and taking it with me.

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.

Dr.GutHealth said:

Steady state is the thing most people miss.

I read this differently from Dr.GutHealth, on substance rather than tone. 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.

Adding the numbers, since they settle part of this. If you are comparing against somebody else’s result, check that you are comparing the same measurement taken the same way. Most of the apparent contradictions in these threads dissolve at that step.

Moderator note: the sourcing question belongs in the vendor section and has been split out.