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ForumsTirzepatide (Mounjaro / Zepbound)5mg doing nothing - should I ask to go up? — anyone have experience?

5mg doing nothing - should I ask to go up? — anyone have experience?

CanadaChris Sun, Aug 4, 2024 at 2:21 PM 11 replies 2,008 viewsPage 1 of 3
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CanadaChris
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Aug 4, 2024 at 2:21 PM#1

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.

So the question, as narrowly as I can put it: whether anyone has held 10mg long term rather than climbing, and what happened over the following year.

If the honest answer is that nobody knows, that is a useful answer and I would rather have it.

22 17Dr.EM_Chicago, pete_RVA, CarlaRPh_TPA and 19 others
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COA_Karl
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Aug 4, 2024 at 3:16 PM#2

This one has a reasonably settled answer, so here it is. 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.

21 16jim_asheville, matt_MKE, Dr.ReproEndo and 18 others
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PharmD_Rodriguez
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Aug 4, 2024 at 4:11 PM#3
COA_Karl 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.

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DadBodDave
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Aug 4, 2024 at 5:06 PM#4
CanadaChris 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.

Can confirm the pattern CanadaChris 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.

Last edited: Aug 4, 2024 at 8:06 PM
19 14Dr.GastroMayo, JakeBK_lifts, DerekSJ_a1c and 16 others
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LindaRN_retired
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Aug 4, 2024 at 10:16 PM#5

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.

18 13mike_nyc, VendorMark, COA_Karl and 15 others
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