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 rather than a lucky one.
Practical numbers: half-life about 5 days, steady state 3 to 4 weeks, ladder 2.5 / 5 / 7.5 / 10 / 12.5 / 15mg, and the maintenance doses with published data behind them are 5, 10 and 15mg.
What would genuinely help is knowing whether anyone has held 10mg long term rather than climbing, and what happened over the following year.
Numbers rather than impressions, if you have them.
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.
LarryQC_SD 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 Resultslucas_SP_BR 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…
Can confirm the pattern lucas_SP_BR describes. 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.
Happy to go further on any of that.
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.