A new meta-analysis of studies of the glucagon-like peptide (GLP)-1 receptor agonist dulaglutide shows that once-weekly treatment with the drug for up to 2 years was not associated with increased risk for cardiovascular events.
“Overall, this cardiovascular meta-analysis suggests that treatment with dulaglutide was not associated with an increase in the risk of experiencing a MACE endpoint compared with comparator therapies,” researcher Keith C. Ferdinand, of Tulane University, and colleagues wrote in Cardiovascular Diabetology. “The incidence of the 4-component MACE in the dulaglutide group over time was consistently lower than the comparator group.”
According to the study, because of the known association between type 2 diabetes and cardiovascular disease, “regulatory agencies now require that the cardiovascular safety of anti-diabetic medications be thoroughly studied prior to regulatory review.”
For this analysis, the researchers included data from 9 studies, which had varied designs, background medication, and comparators. Of the 6010 patients on the randomized studies, 3885 were assigned dulaglutide and 2215 were assigned a comparator therapy. All patients had similar baseline cardiovascular disease characteristics, with the exception of prior myocardial infarction, which was slightly higher in the dulaglutide group (P=0.049).
The researchers were measuring the composite endpoint of death due to cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina.
Of the patients assigned dulaglutide, 0.67% experienced at least one of the four major cardiovascular events compared with 1.18% of patients in the comparator group (hazard ratio [HR]=0.57; 98.02% CI, 0.30-1.10; P=0.046). Additionally, patients assigned dulaglutide had a significantly lower risk of nonfatal myocardial infarction compared with the comparator group (HR=0.35; 98.02% CI, 0.13-0.95; P=0.014). No differences in the risk for death due to cardiovascular causes, nonfatal stroke, or hospitalization for unstable angina were found between the groups.
When the researchers expanded the analysis to compare a 6-component endpoint that added hospitalization for heart failure or coronary revascularization, results were similar with no significant differences found for patients assigned dulaglutide compared with the comparator therapies.
“Recent clinical data indicate that GLP-1 RAs may alter other modifiable cardiovascular risk factors such as body weight, blood pressure, or lipids potentially leading to reduction in macrovascular risk,” the researchers wrote. “It is unknown if these effects would prevent cardiovascular events, this hypothesis remains to be confirmed in long-term cardiovascular outcomes studies.”
According to the study, more definitive data on the relationship between dulaglutide and cardiovascular events will be reported with the on-going REWIND (Researching CV Events with a Weekly Incretin in Diabetes) study.
Ferdinand KC, et al. Cardiovascular safety for once-weekly dulaglutide in type 2 diabetes: a pre-specified meta-analysis of prospectively adjudicated cardiovascular events. Cardiovasc Diabetol. Epub 2016 Feb 24.