Heterogeneity and Similarities in GLP-1 Receptor Agonist Cardiovascular Outcomes Trials

The latest recommendations from the American Diabetes Association and the European Association for the Study of Diabetes prioritize the use of drugs with proven cardiovascular (CV) benefit in patients with established CV disease. Especially among the glucagon-like peptide (GLP)-1 receptor agonists (GLP-1RA) class, results of cardiovascular outcomes trials (CVOT) have been heterogeneous. Baseline characteristics of the population, study design, drugs in the control arm, modifications of CV risk factors, including glycemic control, reduction of hypoglycemia, and the GLP-1RA direct effects on CV cells and tissues, were considered. Ultimately, the time of exposure to the GLP-1RA appears to be the factor most prominently explaining trial heterogeneity. Thus, the CV benefit should be regarded as a class effect of GLP-1RA, as largely similar results are seen for drugs sharing a common mechanism of action.