Trial results comparing Tirzepatide with Dulaglutide in participants with Type 2 Diabetes Mellitus and increased cardiovascular risk were posted on 2026-07-08. The PHASE3 study, NCT04255433, reported that Tirzepatide demonstrated fewer major adverse cardiovascular events (MACE-3) with 801 participants experiencing an event, compared to 862 participants in the Dulaglutide arm.
Background
The trial investigated the efficacy and safety of Tirzepatide compared to Dulaglutide in participants diagnosed with Type 2 Diabetes Mellitus who also had increased cardiovascular risk. Both drugs are used in the management of Type 2 Diabetes.
Trial design
The study, identified as NCT04255433, was a completed PHASE3 trial with an enrollment of 13299 participants. The trial's purpose was to assess the efficacy and safety of Tirzepatide compared to Dulaglutide in participants with Type 2 Diabetes Mellitus and increased cardiovascular risk. Participants were randomized to receive either Tirzepatide (MTD) or 1.5 mg Dulaglutide.
Key results
Key results from the trial focused on major cardiovascular events and mortality outcomes. For the composite endpoint of major adverse cardiovascular events (MACE-3), which includes death from cardiovascular causes, myocardial infarction, or stroke, 801 participants in the Tirzepatide (MTD) group experienced an event, compared to 862 participants in the 1.5 mg Dulaglutide group.
Regarding all-cause death, 566 participants in the Tirzepatide (MTD) arm experienced this outcome, versus 669 participants in the 1.5 mg Dulaglutide arm. Cardiovascular death occurred in 367 participants receiving Tirzepatide (MTD), compared to 408 participants receiving 1.5 mg Dulaglutide.
For specific cardiovascular events, myocardial infarction (MI) was reported in 311 participants treated with Tirzepatide (MTD) versus 357 participants treated with 1.5 mg Dulaglutide. Stroke occurred in 229 participants in the Tirzepatide (MTD) group, compared to 249 participants in the 1.5 mg Dulaglutide group.
An expanded composite endpoint (MACE-4), including CV death, MI, stroke, or coronary revascularization, was observed in 1089 participants in the Tirzepatide (MTD) group and 1217 participants in the 1.5 mg Dulaglutide group.
What this means
The posted trial results indicate that Tirzepatide demonstrated numerically fewer major adverse cardiovascular events and mortality outcomes compared to Dulaglutide in participants with Type 2 Diabetes Mellitus and increased cardiovascular risk. The differences observed across MACE-3, all-cause death, cardiovascular death, myocardial infarction, and stroke suggest a potential advantage for Tirzepatide in reducing these critical events. These findings provide important comparative data for clinicians considering treatment options for patients with Type 2 Diabetes who are at risk for cardiovascular complications.
Source
These trial results were posted on ClinicalTrials.gov on 2026-07-08. The full details of the study, NCT04255433, are available on clinicaltrials.gov.