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ForumsTirzepatide (Mounjaro / Zepbound)Switching from sema to tirz and WOW the difference — what worked for you?

Switching from sema to tirz and WOW the difference — what worked for you?

COA_Karl Thu, Aug 7, 2025 at 10:38 PM 13 replies 1,517 viewsPage 1 of 3
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COA_Karl
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Aug 7, 2025 at 10:38 PM#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.

The narrow version of the question is 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.

19 22matt_MKE, Dr.ReproEndo, lucas_SP_BR and 16 others
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anders_CPH
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Aug 7, 2025 at 10:44 PM#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.

20 23MariaRD, AussieAnna, BethLabQueen and 17 others
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hans_munich
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Aug 7, 2025 at 10:50 PM#3
anders_CPH 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.

21 24Dr.LipidDallas, alex_tucson, kevin_tulsa and 18 others
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MeganSA_TX
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Aug 7, 2025 at 10:56 PM#4
COA_Karl 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…

This matches mine closely enough to be worth saying so. 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.

22 0TomFromTexas, mike.trainer_LA, sarah_nash92 and 19 others
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sophie_paris
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Aug 7, 2025 at 11:28 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.

23 1BethLabQueen, ChrisMacros, KetoKyle and 20 others
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