Insights From Cardiovascular Outcome Trials with Novel Antidiabetes Agents: What Have We Learned? An Industry Perspective

Boaz Hirshberg, Arie Katz

Owing to the close association of cardiovascular (CV) disease with type 2 diabetes and the uncertainty surrounding the CV safety of antidiabetes agents, in 2008 the Food and Drug Administration issued guidance for the demonstration of CV safety for new antidiabetes drugs. Recently the results from CV outcomes trials of three dipeptidyl peptidase-4 (DPP-4) inhibitors and a glucagon-like peptide-1 receptor agonist have been reported. The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) trial, the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome (EXAMINE) trial, and the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) assessed the safety of saxagliptin, alogliptin, and sitagliptin, respectively, in patients with type 2 diabetes with CV disease or at high risk for CV disease. The Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) assessed the safety of lixisenatide in patients with type 2 diabetes and a recent acute coronary syndrome event. The results show that these agents neither increased nor deceased major adverse CV events (CV death, nonfatal myocardial infarction, and nonfatal stroke) compared with placebo. However, the resources needed to conduct these studies may detract from the ability to understand the potential long-term benefit and risk in the majority of patients that are candidates for use of these medications.