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ForumsMetabolic Health & DiabetesSURPASS-CVOT: tirzepatide cardiovascular outcomes trial design — need advice Page 3

SURPASS-CVOT: tirzepatide cardiovascular outcomes trial design — need advice

GenomicsKate Sat, Jan 3, 2026 at 11:59 AM 29 replies 1,587 viewsPage 3 of 6
BiostatsBrad
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Jan 6, 2026 at 12:42 PM#11
TinaHashiRN 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.

Thank you — that is the clearest version of this I have read, and I have read a lot of them. Printing the relevant bit and taking it with me.

39 12LindaRN_retired, tommy_boulder, hyun_seoul and 36 others
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Dr.ObesityMed
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Jan 7, 2026 at 3:28 PM#12

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.

40 13PharmacoVig_BOS, SurmountFan_IN, PeptideChemSF and 37 others
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Dr.LipidDallas
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Jan 8, 2026 at 6:14 PM#13
LindaRN_retired said:
SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

This is where I part company with the consensus forming above. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.

41 14cory_ATX, lori_vegas, Dr.PulmRoch and 38 others
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Dr.GutHealth
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Jan 9, 2026 at 8:59 PM#14

One concrete data point for the thread. One practical note: write down what you did and when, before you need it. Reconstructing a timeline from memory three months later is how people end up unable to answer the one question that would have resolved it.

Worth separating that from cardiovascular outcomes, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.

Last edited: Jan 10, 2026 at 1:59 AM
42 15Dr.RaviCardio, jennifer_SEA, tyler_CSCS and 39 others
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mike_mod
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Jan 10, 2026 at 11:43 PM#15

Moderator note: reminder that nothing in this thread is medical advice, and that clinical claims need a source. Thread quality here is what the rules are for. Keep it up.

Last edited: Jan 11, 2026 at 1:43 AM
43 16PurityPaulOR, MaxMetOK, MounjBrad and 40 others
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