SURPASS-CVOT: tirzepatide noninferior to dulaglutide

Theme

Tirzepatide vs dulaglutide in high-risk type 2 diabetes

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

Source
Source: NEJM publication of the SURPASS-CVOT trial comparing tirzepatide versus dulaglutide for cardiovascular outcomes in patients with type 2 diabetes and atherosclerotic cardiovascular disease.

Active-comparator cardiovascular outcomes evidence in patients with type 2 diabetes and established atherosclerotic cardiovascular disease.

Trial at a glance
Active-comparator CVOT
Double-blind design
Type 2 diabetes
Established ASCVD
Tirzepatide
Investigational arm
Dulaglutide
Active comparator
Primary cardiovascular result
HR 0.92
3-point MACE: cardiovascular death, myocardial infarction, or stroke
95.3% CI 0.83–1.01
Confidence interval crosses 1.00 for superiority testing.
Noninferiority met
Superiority not statistically confirmed.
Effect estimate with confidence interval

Comparable major cardiovascular event protection

Null line = HR 1.00
Observed primary endpoint events

3-point MACE event percentages

12.2%
Tirzepatide
13.1%
Dulaglutide
Modified intention-to-treat population

Patients analyzed

13,165
Patients in the modified intention-to-treat population
Tirzepatide
6,586
Dulaglutide
6,579
Patient profile

High-risk cardiometabolic population

Participants were older, had long-duration diabetes, obesity, elevated HbA1c, and established cardiovascular disease.
64.1
Mean age, years
32.6
Mean BMI
8.4%
Mean HbA1c
14.7
Mean diabetes duration, years
Safety signal

Adverse-event pattern

Overall adverse events similar
No broad excess in overall adverse events was highlighted versus dulaglutide.
Gastrointestinal events more frequent
GI tolerability remains a practical monitoring point with tirzepatide.
Numbers to know

Core clinical readout

0.92
Hazard ratio for MACE
0.83–1.01
95.3% CI
6,586
Tirzepatide patients
6,579
Dulaglutide patients
Takeaway
For patients with type 2 diabetes and established atherosclerotic cardiovascular disease, tirzepatide can be framed as cardiovascularly noninferior to dulaglutide, with CV safety and comparable protection demonstrated — superiority not confirmed.
AbbreviationsQuick
Abbreviations: SURPASS-CVOT = SURPASS cardiovascular outcomes trial; DOI = digital object identifier; PMID = PubMed identifier.
Bibliography1
  1. Nicholls SJ, Pavo I, Bhatt DL, et al.; SURPASS-CVOT Investigators. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. N Engl J Med. 2025 Dec 18;393(24):2409-2420. (DOI: 10.1056/NEJMoa2505928)
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