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ForumsDosing & ProtocolsPK/PD modeling for tirzepatide — anyone have experience?

PK/PD modeling for tirzepatide — anyone have experience?

CryptoCarl Sat, Jan 10, 2026 at 5:27 AM 24 replies 1,368 viewsPage 1 of 5
CryptoCarl
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Jan 10, 2026 at 5:27 AM#1

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.

The bit I cannot resolve on my own is whether anyone has held 10mg long term rather than climbing, and what happened over the following year.

I would rather have one careful answer than five confident ones.

30 0CryptoCarl, MariaRD, AussieAnna and 27 others
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Dr.ObesityMed
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Jan 10, 2026 at 5:56 AM#2

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.

29 24PharmacoVig_BOS, SurmountFan_IN, PeptideChemSF and 26 others
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BenResearch_OR
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Jan 10, 2026 at 6:25 AM#3
Dr.ObesityMed 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.

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.

28 23Dr.NateNeph, PharmD_Rodriguez, julia.endo and 25 others
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dave_SLC
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Jan 10, 2026 at 6:54 AM#4
CryptoCarl 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…

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.

Correct me if the detail matters more than I have assumed.

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Dr.LipidDallas
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Jan 10, 2026 at 9:32 AM#5

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.

Last edited: Jan 10, 2026 at 11:32 AM
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