Cardiovascular Effects of Diabetes Drugs: Making the Dark Ages Brighter With CAROLINA

TO THE EDITOR:

We read Nissen's recent editorial (1) on Roumie and colleagues' study (2) with great interest. We agree entirely with Nissen that the evidence base to guide clinical decision making in type 2 diabetes mellitus currently suffers from the absence of a rigorous, randomized, controlled trial (RCT) that addresses the sulfonylurea controversy. Not only are there conflicting results between older and more recent trials using sulfonylureas, but observational studies also are not concordant (2, 3). Indeed, even with the best biostatistics and methods, no epidemiologic, observational retrospective, or prospective cohort study can replace a properly conducted RCT.

Nissen rightfully called for an RCT to evaluate the effect of sulfonylureas on cardiovascular disease outcomes. We welcome his call and are pleased to inform that there currently is an ongoing RCT specifically designed and properly powered to address the sulfonylurea controversy—CAROLINA (Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes; ClinicalTrials.gov NCT01243424). This study is a double-blind, double-dummy RCT that began in November 2010 and recently met the target recruitment number of 6000 patients with relatively early type 2 diabetes mellitus who are also at high risk for or already have evidence of cardiovascular complications. Because this study will explore potential effects on cardiovascular outcomes of linagliptin versus glimepiride therapy, predominantly as an add-on to metformin, its results may provide firm evidence to aid future clinical decision making when selecting second-line therapy for patients with type 2 diabetes mellitus. CAROLINA is addressing an important piece of the large gap of data from comparative effectiveness studies in diabetes, as recognized by Nissen (1) and others (4, 5). It hopefully will help us move toward the “age of enlightenment” for selecting therapeutic strategies in the high-risk population of patients with diabetes.