Treatment with tirzepatide, a dual GLP-1* and GIP** agonist, significantly improves cardiovascular and renal outcomes in patients with diabetes and atherosclerotic cardiovascular disease (ASCVD) compared with dulaglutide, according to a post hoc analysis of the SURPASS-CVOT trial presented at ACC.26.
After a median treatment duration of 46.9 months, the primary composite of six-component cardiorenal endpoint (ie, all-cause mortality, myocardial infarction, stroke, coronary revascularization, hospitalization for heart failure, and adverse renal outcomes) occurred in 23.7 percent of patients treated with tirzepatide compared with 27.4 percent of those treated with dulaglutide (hazard ratio [HR], 0.84; p<0.001). [ACC 2026, abstract 216-07]
The analysis of the individual components of the primary composite outcome revealed that the observed effect was primarily driven by lower rates of all-cause mortality (8.6 percent vs 10.2 percent; HR, 0.84), coronary revascularization (8 percent vs 9.4 percent; HR, 0.84), and the composite renal endpoint (4.9 percent vs 6.1 percent; HR, 0.79) in the tirzepatide group compared with the dulaglutide group.
This finding was further supported by a sensitivity analysis using a narrower five-component endpoint, excluding renal outcomes, which demonstrated a significantly lower rate of the five-component outcome with tirzepatide compared with dulaglutide (HR, 0.86; p<0.001).
Furthermore, when renal outcomes and heart failure events were omitted, a four-component outcome demonstrated a lower incidence with tirzepatide than with dulaglutide (HR, 0.86; p<0.001).
Importantly, all-cause mortality, a key driver of improved outcomes, was significantly reduced in the tirzepatide group relative to the dulaglutide group (HR, 0.84; p=0.002).
Overall, “in patients with diabetes and ASCVD, tirzepatide, compared with dulaglutide, was associated with a lower incidence of a broad six-component cardiorenal endpoint,” said lead author Dr Steven Nissen from the Cleveland Clinic Coordinating Center for Clinical Research in Ohio, US.
Of note, “in the SURPASS-CVOT trial, dulaglutide was chosen as the comparator because it reduced CV events in the REWIND trial and was available in a visibly identical injector to tirzepatide,” he said.
SURPASS-CVOT trial included patients (mean age 64 years, 81.5 percent female) with diabetes (mean HbA1c 8.4 percent) and established ASCVD who were randomized in a 1:1 ratio to receive either tirzepatide 15 mg (n=6,586) or dulaglutide 1.5 mg (n=6,579) weekly.
In this current analysis, the most common adverse event (AE) observed was gastrointestinal disorders, which occurred more frequently in tirzepatide-treated patients than in dulaglutide-treated patients (42.5 percent vs 35.9 percent).
Nissen pointed out that this result was also seen in the main SURPASS-CVOT trial and was not a new finding.
In addition, Nissen said that highly effective incretin therapies for diabetes and obesity are now available with additional drugs in development. These treatments offer a wide range of benefits for patients and represent a new paradigm for reduction in multiple cardiorenal adverse outcomes.