SURPASS-CVOT: tirzepatide noninferior to dulaglutide

Theme

Cardiovascular outcomes in high-risk type 2 diabetes

Tirzepatide matched dulaglutide for major cardiovascular outcomes — but did not prove superiority.

Source
Source: Extracted MEDLINE-style record and abstract for the SURPASS-CVOT trial publication in N Engl J Med comparing tirzepatide versus dulaglutide in type 2 diabetes with atherosclerotic cardiovascular disease.

In adults with type 2 diabetes and established atherosclerotic cardiovascular disease, tirzepatide was cardiovascularly noninferior to dulaglutide, an active comparator with known cardiovascular benefit.

HR 0.92
Major cardiovascular events
95.3% CI: 0.83–1.01
Interpretation: noninferior; not statistically superior
Design
Randomized active-comparator cardiovascular outcomes trial
Population
Adults with type 2 diabetes + established ASCVD
Intervention
Tirzepatide up to 15 mg once weekly
Comparator
Dulaglutide 1.5 mg once weekly; active comparator with CV benefit
Primary outcome

CV death, myocardial infarction, or stroke

Met noninferiority Superiority not proven

The confidence interval narrowly crossed 1.00, supporting cardiovascular comparability but not a statistically superior reduction in major adverse cardiovascular events.

Effect estimate

Forest-style view of the primary endpoint

0.92
HR vs dulaglutide
Reference line at HR 1.00. CI upper bound of 1.01 means statistical superiority was not demonstrated.
Observed primary event rates

MACE occurred in nearly similar proportions

12.2%
Tirzepatide
13.1%
Dulaglutide
Safety signal

Overall adverse-event rates were similar, but gastrointestinal events were more frequent

Similar
overall adverse-event rates
More GI
events with tirzepatide

Safety interpretation should balance cardiovascular comparability with tolerability counseling, especially nausea, vomiting, diarrhea, and other gastrointestinal adverse events.

Key findings

Exact clinical numbers

Modified intention-to-treat population
Measure Tirzepatide Dulaglutide Effect / interpretation
Patients assigned 6,586 6,579 13,165 total in the modified intention-to-treat population
Primary CV event
CV death, MI, or stroke		 12.2% 13.1% HR 0.92; 95.3% CI 0.83–1.01
Cardiovascular conclusion Noninferior to dulaglutide Did not meet statistical superiority
Safety Similar overall adverse-event rates Gastrointestinal events occurred more frequently with tirzepatide
Numbers to know
13,165
patients in modified intention-to-treat population
64.1
years mean age
32.6
mean BMI
8.4%
mean HbA1c
14.7
years mean diabetes duration
95.3% CI 0.83–1.01
confidence interval for HR 0.92
Clinical takeaway

For patients with type 2 diabetes and established cardiovascular disease, tirzepatide demonstrated cardiovascular outcomes comparable to dulaglutide while offering its known metabolic benefits on weight and glycemic control.

Emphasize: noninferior, not proven superior — and balance efficacy messaging with the higher frequency of gastrointestinal adverse events.

AbbreviationsQuick
Abbreviations: DOI, digital object identifier; N Engl J Med, New England Journal of Medicine; PMID, PubMed identifier; SD, standard deviation; SURPASS-CVOT, trial name as cited.
Bibliography1
  1. Nicholls SJ, Pavo I, Bhatt DL, Buse JB, Del Prato S, Kahn SE, et al.; SURPASS-CVOT Investigators. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. N Engl J Med. 2025;393(24):2409-2420. (DOI: 10.1056/NEJMoa2505928)
👀 View Mode