Effect of Once‐Weekly Exenatide on Clinical Outcomes According to Baseline Risk in Patients With Type 2 Diabetes Mellitus: Insights From the EXSCEL Trial

Background In the EXSCEL (Exenatide Study of Cardiovascular Event Lowering), exenatide once‐weekly resulted in a nonsignificant reduction in major adverse cardiovascular events (MACEs) and a nominal 14% reduction in all‐cause mortality in 14 752 patients with type 2 diabetes mellitus (T2DM) with and without cardiovascular disease. Whether patients at increased risk for events experienced a comparatively greater treatment benefit with exenatide is unknown. Methods and Results In the EXSCEL population, we created risk scores for MACEs and all‐cause mortality using step‐wise selection of baseline characteristics. A risk score was calculated for each patient, and a time‐to‐event model for each end point was developed including the risk score, treatment assignment, and risk‐treatment interaction. Interaction P values evaluating for a differential treatment effect by baseline risk were reported. Over a median follow‐up of 3.2 years (interquartile range, 2.2, 4.4), 1091 (7.4%) patients died and 1744 (11.8%) expe...