Following the CV safety concerns with rosiglitazone especially new incidence of heart failure, the FDA mandated that all new diabetes drugs conduct studies demonstrating CV safety. SAVOR-TIMI trial sought to study the cardiovascular (CV) safety of saxagliptin in patients with type 2 diabetes mellitus (DM2). Saxagliptin is a novel selective dipeptidyl peptidase 4 (DPP-4) inhibitor that lowers glucose. 16,492 patients with DM2, age ≥40 years, and documented HbA1c ≥6.5% in the previous 6 months, and high risk for a CV event with either established CV disease, or multiple risk factors were randomized to saxagliptin or placebo. The primary outcome of the composite of CV death/nonfatal MI/nonfatal stroke was no different in both groups. (P<0.001 for noninferiority). The authors of the SAVOR-TIMI trial concluded that DPP-4 inhibition with saxagliptin did not affect the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce CV risk in patients with diabetes.