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ForumsCardiovascular OutcomesTirzepatide cardiovascular safety — SURPASS-CVOT design analysis Page 3

Tirzepatide cardiovascular safety — SURPASS-CVOT design analysis

TrialTracker_MD Mon, May 25, 2026 at 5:23 AM 14 replies 586 viewsPage 3 of 3
ben_calgary
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May 26, 2026 at 3:38 PM#11
NurseLeah_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.

Thank you for spelling out the reasoning rather than just the conclusion. I will report back once I have actually tried it.

19 19KetoKyle, CanadaChris, ZaraB_AL and 16 others
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Dr.NateNeph
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May 27, 2026 at 9:33 PM#12

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.

Last edited: May 27, 2026 at 11:33 PM
18 18NauseaFreeNow, SteveThurs, B12Beth and 15 others
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FDA_TrackerJim
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May 29, 2026 at 3:29 AM#13
chris_chi24 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…

Pushing back on chris_chi24 here. 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.

17 17MikeNYC_runner and 14 others
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Dr.PathRoch
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May 30, 2026 at 9:25 AM#14

The figures, for anyone assembling their own picture. Keep the original post as written when you update it, and add the correction underneath. An edited-away mistake is invisible to the next person who makes it.

Last edited: May 30, 2026 at 3:25 PM
16 16SaraMom3, Dr.MetabolicMD, RetaRick_CA and 13 others
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mike_mod
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May 31, 2026 at 3:22 PM#15

Moderator note: reminder that nothing in this thread is medical advice, and that clinical claims need a source. Tagging this one for the weekly digest.

15 15PurityPaulOR, MaxMetOK, MounjBrad and 12 others
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