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Evidence-based GLP-1 & peptide discussion since 2023
ForumsTirzepatide (Mounjaro / Zepbound)Tirz made me a completely different person holy cow — looking for input

Tirz made me a completely different person holy cow — looking for input

roxy_nash Wed, Sep 10, 2025 at 7:43 PM 35 replies 1,765 viewsPage 1 of 7
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roxy_nash
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Sep 10, 2025 at 7:43 PM#1

Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using it.

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.

Where I think it is weakest: the population was selected and supported in ways a real cohort is not, so I would read the effect size as a ceiling rather than an expectation.

What I am trying to establish is whether anyone has held 10mg long term rather than climbing, and what happened over the following year. Practical detail welcome, however dull — the duller the better.

Note on sourcing:
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
34 12josh_phd_bmore, roxy_nash, tony_orlando and 31 others
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Dr.NateNeph
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Sep 10, 2025 at 7:48 PM#2
roxy_nash said:
SURMOUNT-1 landed around 20.9% mean weight loss at 15mg over 72 weeks, against roughly 15% for semaglutide 2.4mg in STEP 1.

That is correct as far as it goes, and here is where it stops going. The GIP arm is doing real work rather than padding the label. GIP receptor agonism appears to improve adipose insulin sensitivity and lipid handling, and — counter-intuitively — GIP signalling in the CNS reduces nausea rather than adding to it, which is why tolerability at high total agonism is better than the GLP-1-only comparison would predict. SURPASS-2 is the cleanest head-to-head: tirzepatide beat semaglutide 1mg at every dose tier.

Happy to go further on any of that.

Last edited: Sep 10, 2025 at 9:48 PM
35 13NauseaFreeNow, SteveThurs, B12Beth and 32 others
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LarryQC_SD
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Sep 10, 2025 at 7:53 PM#3
roxy_nash said:
SURMOUNT-1 landed around 20.9% mean weight loss at 15mg over 72 weeks, against roughly 15% for semaglutide 2.4mg in STEP 1.

This is where I part company with the consensus forming above. The "tirzepatide is simply better" summary irritates me. It is better on mean weight loss, and the cardiovascular outcome evidence is far thinner than semaglutide's. If the reason for treating is cardiovascular risk rather than weight, the evidence base points the other way.

36 14TinaHashiRN, robert_kc, dan_philly and 33 others
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sean_dublin
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Sep 10, 2025 at 7:58 PM#4

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.

37 15NurseLeah_Nash, gary_naperville, sean_dublin and 34 others
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JessicaM_2024
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Sep 10, 2025 at 8:24 PM#5
Dr.NateNeph said:
The GIP arm is doing real work rather than padding the label.

Second this. Nothing to add that would improve it.

38 16kevin_tulsa, Dr.PainCLE, mike_mealprep and 35 others
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