title: Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: rationale for the active-comparator CAROLINA trial.
abstract: Sulphonylureas (SUs) are widely used glucose-lowering agents in type 2 diabetes mellitus (T2DM) with apparent declining efficacy over time. Concerns have been raised from observational retrospective studies on the cardiovascular (CV) safety of SUs but there are few long-term data on CV outcomes from randomized controlled trials (RCTs) involving the use of this class of agents. Most of the observational studies and registry data are conflicting and vary with study population and methodology used for analyses. To address the SU controversy, we reviewed the recently published literature (until end of the year 2011) to evaluate the impact of SUs on CV outcomes in modern, longer-term (≥72 weeks) RCTs where they were compared in a head-to-head fashion versus an active comparator or were used as part of a treatment strategy. We identified 15 trials and found no report of an increase in the incidence of CV events with the use of SUs. However, the available data are limited, and, most importantly, there was no adequately powered formal head-to-head CV outcome trial designed to address CV safety. Since SUs are still being advocated as second-line therapy added-on to metformin, as one of several classes, and in certain circumstances first-line therapy in T2DM management, definitive data from a dedicated RCT addressing the CV safety question with SUs would be informative. Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients with Type 2 Diabetes (CAROLINA) is such a trial, ongoing since November 2010, and is currently the largest head-to-head CV outcome trial that involves a comparison of a SU (glimepiride) with a dipeptidyl peptidase-4 (DPP-4) inhibitor (linagliptin) and will provide a unique perspective with respect to CV outcomes with these two commonly used agents.
authors: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA.
authors: Julio
authors: J
authors: Rosenstock
authors: Nikolaus
authors: N
authors: Marx
authors: Steven E
authors: SE
authors: Kahn
authors: Bernard
authors: B
authors: Zinman
authors: John J
authors: JJ
authors: Kastelein
authors: John M
authors: JM
authors: Lachin
authors: Erich
authors: E
authors: Bluhmki
authors: Sanjay
authors: S
authors: Patel
authors: Odd-Erik
authors: OE
authors: Johansen
authors: Hans-Jürgen
authors: HJ
authors: Woerle
mesh_terms: D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds
keywords: Type 2 diabetes mellitus; cardiovascular disease; dipeptidyl peptidase-4 inhibitor; oral glucose-lowering agent; sulphonylurea