Fourteen months on tirzepatide, currently 10mg, and I stopped escalating because 10mg is doing the job and 15mg made me feel flat rather than full.
The narrow version of the question is 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.
Practical detail welcome, however dull — the duller the better.
Taking the question as asked, rather than the general version of it. 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.
SarahChen_PharmD said: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.
Agreed on the mechanism, with the caveat that the head-to-head used semaglutide 1mg, not 2.4mg. It is still the best direct evidence available, but it is not the comparison most people think they are citing.
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View ResultsSallyK_inj said:Fourteen months on tirzepatide, currently 10mg, and I stopped escalating because 10mg is doing the job and 15mg made me feel flat rather than full.
Same position here, arrived at the long way round. SURMOUNT-1 landed around 20.9% mean weight loss at 15mg over 72 weeks, against roughly 15% for semaglutide 2.4mg in STEP 1. Different trials, different populations, so the comparison is indicative rather than decisive — but SURPASS-2 was a genuine head-to-head and it pointed the same way.
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.