[Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: Rationale for the active-comparator CAROLINA® trial].

Sulphonylureas (SUs) are antidiabetic agents widely used in patients with Type 2 Diabetes Mellitus (T2DM). Observational retrospective studies have raised concerns regarding the cardiovascular (CV) safety of this class of drugs, and data from observational and registry studies are conflicting. To address the SU controversy, this review looked at longer-term RCTs, where SUs were compared in a head-to-head fashion with active comparators. An analysis of 18 studies did not find any increase in the incidence of CV events with SU therapy. However, the available data are limited and most importantly, there is a lack of prospective, adequately powered, formal head-to-head CV outcome trials. Since SUs are still being used as second-line therapy in combination with metformin and in some cases as first-line treatment of T2DM, there is a definite need for CV safety data from a prospective RCT. The CAROLINA(®) study is currently the largest CV outcome study with a direct comparison of an SU and a dipeptidyl peptidase-4 inhibitor (DPP-4). Based on the study design and statistical power of CAROLINA(®), its results will provide a unique perspective regarding CV outcomes of these 2 commonly used agents.