Document Type

Journal Article

Publication Date



Diabetes and Vascular Disease Research


Volume 10, Issue 4

Inclusive Pages



Cardiovascular Diseases--drug therapy; Diabetes Mellitus, Type 2--drug therapy; Hypoglycemic Agents--therapeutic use; Randomized Controlled Trials as Topic; Sulfonylurea Compounds--therapeutic use


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.


Reproduced with permission of Sage, Diabetes & Vascular Research.

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This work is licensed under a Creative Commons Attribution 3.0 License.

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Open Access