Phase 3 CVOT — Tirzepatide (Mounjaro)
SURPASS-CVOT: trial summary, limitations and UK relevance
SURPASS-CVOT compared tirzepatide with dulaglutide in adults with type 2 diabetes and established ASCVD and demonstrated non-inferiority for the primary MACE-3 endpoint. Superiority over dulaglutide for the primary endpoint should not be implied unless directly supported by the cited primary publication.
Key findings
SURPASS-CVOT compared tirzepatide with dulaglutide in adults with type 2 diabetes and established ASCVD and demonstrated non-inferiority for the primary MACE-3 endpoint. Superiority over dulaglutide for the primary endpoint should not be implied unless directly supported by the cited primary publication.
Safety summary
GI adverse events were more frequent with tirzepatide than dulaglutide, consistent with the wider class profile. No novel cardiovascular safety signals were reported in the primary release.
Limitations
- Active-comparator design (dulaglutide), not placebo — relative comparison only.
- Population is T2D + ASCVD; generalisability to non-diabetic obesity CVD prevention is limited.
- MACE-3 primary endpoint does not capture all clinically relevant cardiovascular events.
UK relevance
Directly relevant to UK MHRA / NICE consideration of tirzepatide in adults with type 2 diabetes and established cardiovascular disease, and to clinical decisions in NHS diabetes pathways where active GLP-1 RA comparators are routine.
- Non-inferiority versus dulaglutide does not establish superiority for the primary endpoint.
- T2D + ASCVD trial findings do not directly establish cardiovascular benefit in non-diabetic obesity (separate trials in obesity populations are required).
- Active-comparator design means results should not be reinterpreted as if placebo-controlled.
Frequently asked questions
What does non-inferiority mean in SURPASS-CVOT?
Non-inferiority means the trial was designed to show that tirzepatide was not meaningfully worse than dulaglutide for the primary MACE-3 endpoint, not that it was superior. A non-inferiority result confirms an acceptable safety margin versus the active comparator but does not establish tirzepatide as superior to dulaglutide for cardiovascular events.
How does SURPASS-CVOT compare with SELECT?
The trials answer different questions. SURPASS-CVOT compared tirzepatide with dulaglutide (active GLP-1 agonist) in adults with type 2 diabetes and established ASCVD. SELECT compared semaglutide with placebo in adults with overweight or obesity and established CVD without diabetes. Direct cross-trial comparison requires caution given differing populations, comparators and designs.
Related peptide profiles
Related trials
Related conditions
Related mechanisms
Related safety signals
Sources are tagged by class. Regulatory documents, peer-reviewed publications and trial registry records are preferred. Manufacturer disclosures and conference material are accepted where peer-reviewed publication is not yet available; preprints are flagged.
- Manufacturer scientific disclosureEli Lilly investor disclosure on SURPASS-CVOT topline results
- Trial registry recordClinicalTrials.gov NCT04255433