SURPASS-CVOT Trial Summary
SURPASS-CVOT is an ongoing, event-driven cardiovascular outcomes trial comparing tirzepatide (a dual GIP/GLP-1 receptor agonist) to dulaglutide 1.5 mg in patients with type 2 diabetes and established atherosclerotic cardiovascular disease, designed to assess both noninferiority and superiority for major adverse cardiovascular events. 1
Trial Design and Status
Study Type: Randomized, double-blind, active-controlled cardiovascular outcomes trial comparing tirzepatide (up to 15 mg weekly) versus dulaglutide 1.5 mg weekly 1
Enrollment: Fully recruited with 13,299 participants randomized across 640 sites in 30 countries over approximately 2 years 1
Current Status: The trial is ongoing and event-driven, planned to continue until at least 1,615 participants experience an adjudication-confirmed major adverse cardiovascular event (MACE) 1
Patient Population Characteristics
Baseline demographics reveal a high-risk population:
- Mean age 64.1 years with mean diabetes duration of 14.7 years 1
- Mean HbA1c 8.4% and mean BMI 32.6 kg/m² 1
- Cardiovascular disease burden: 65.0% had coronary disease, with 47.3% reporting prior myocardial infarction and 57.4% having prior coronary revascularization 1
- 19.1% had prior stroke and 25.3% had peripheral artery disease 1
Inclusion criteria required:
- Age ≥40 years with type 2 diabetes 1
- Established atherosclerotic cardiovascular disease 1
- HbA1c ≥7% to ≤10.5% 1
- Body mass index ≥25 kg/m² 1
Primary and Secondary Outcomes
Primary Outcome: Time to first occurrence of MACE, defined as the composite of cardiovascular death, myocardial infarction, or stroke 1
Primary Analysis Strategy:
- Noninferiority analysis: Demonstrating upper confidence limit <1.05 for tirzepatide versus dulaglutide, which will also confirm superiority versus a putative placebo 1
- Superiority analysis: Determining whether tirzepatide produces greater cardiovascular benefit than dulaglutide 1
Context Within GLP-1 Receptor Agonist Evidence
This trial is unique as an active-controlled comparison:
Unlike previous GLP-1 receptor agonist cardiovascular outcomes trials (LEADER, SUSTAIN-6, REWIND, PIONEER-6) that compared against placebo 2, SURPASS-CVOT directly compares tirzepatide to dulaglutide, a GLP-1 receptor agonist with established cardiovascular benefit 1
Dulaglutide's established benefits from the REWIND trial include: 12% reduction in MACE (HR 0.88,95% CI 0.79-0.99) over median 5.4 years follow-up, with benefits seen in both patients with and without established cardiovascular disease 2, 3
The choice of dulaglutide as the active comparator provides a higher bar for demonstrating cardiovascular benefit compared to placebo-controlled trials 1
Clinical Implications Pending Results
When results become available, SURPASS-CVOT will:
Provide definitive evidence on cardiovascular safety and efficacy of tirzepatide, a dual GIP/GLP-1 receptor agonist, compared to an established GLP-1 receptor agonist 1
Inform whether the dual incretin mechanism offers additional cardiovascular protection beyond GLP-1 receptor agonism alone 1
Guide treatment decisions for patients with type 2 diabetes and established atherosclerotic cardiovascular disease, particularly regarding choice between tirzepatide and GLP-1 receptor agonists 1
Current guideline recommendations favor GLP-1 receptor agonists for patients with type 2 diabetes and established atherosclerotic cardiovascular disease to reduce MACE, with the strongest evidence for liraglutide, semaglutide, and dulaglutide 2. SURPASS-CVOT results will determine whether tirzepatide should be added to this list and whether it offers superior cardiovascular protection 1.