Cardiovascular disease is responsible for 205 deaths per 100,000 persons annually and is the leading cause of death worldwide. The public health burden of cardiovascular disease is expected to continue to grow as the prevalence of many cardiovascular risk factors increases. Several novel classes of glucose-lowering, lipid-lowering, and weight-loss therapeutics have shown mortality benefits in outcomes trials. However, a large proportion of subjects in those trials had established cardiovascular disease, so, as a result, the role of these novel therapeutics in primary cardiovascular prevention is controversial.