EndoResFellow 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.
Clinical perspective, offered as context rather than as advice.
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.
james_edin said:The mechanism is more central than most summaries suggest.
I am going to disagree with the direction of travel here. The thread has converged on the tidiest answer rather than the best-supported one, and those are not the same thing.
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Browse GL BiochemThe figures, for anyone assembling their own picture. The boring version of this is the one that works, and the boring version is: measure a baseline, change one variable, wait, measure again under the same conditions. Nobody wants that answer and it is still the answer.
Moderator note: reminder that nothing in this thread is medical advice, and that clinical claims need a source. Report rather than reply if it drifts again.