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Evidence-based GLP-1 & peptide discussion since 2023
ForumsCardiovascular OutcomesHas anyone dealt with apob reduction on tirzepatide?

Has anyone dealt with apob reduction on tirzepatide?

tampaLisa73 Sat, Apr 26, 2025 at 11:05 AM 41 replies 2,416 viewsPage 1 of 9
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tampaLisa73
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Apr 26, 2025 at 11:05 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.

What I am trying to establish 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.

I have searched first, so if this is covered somewhere point me at it and I will read it.

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Dr.MetabolicMD
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Apr 26, 2025 at 12:04 PM#2

Answering the narrow version, because the broad one does not have a single answer. 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.

Last edited: Apr 26, 2025 at 2:04 PM
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DanielChem_CHI
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Apr 26, 2025 at 1:03 PM#3
Dr.MetabolicMD 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.

Last edited: Apr 26, 2025 at 3:03 PM
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PedsEndoPhilly
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Apr 26, 2025 at 2:02 PM#4
tampaLisa73 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.

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LibrarianMeg
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Apr 26, 2025 at 7:41 PM#5

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.

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