The effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2i) highlights the importance of well-powered clinical trials that have identified a new treatment strategy for type 2 diabetes, according to a state-of-the-art review published July 31 in the Journal of the American College of Cardiology.

Thomas A. Zelniker, MD, MSc, and Eugene Braunwald, MD, MACC, discuss how type 2 diabetes is a rapidly growing major global health problem, leading to an increased risk of coronary and other arterial events, heart failure, decline in renal function and death. Until recently, the authors note that trials for the approval of anti-diabetic drugs underpowered changes in macrovascular events such as myocardial infarction, stroke or cardiovascular death.

After several large cardiovascular outcome trials with mostly neutral results, the authors point out two studies of SGLT2i – the EMPA-REG OUTCOME trial looking at empagliflozin, and the CANVAS trial looking at canagliflozin – that reported favorable effects on a composite of myocardial infarction, stroke and cardiovascular death. In addition, the studies found reductions of hospitalizations for heart failure and, in the case of empagliflozin, reductions in both cardiovascular and total mortality.

The authors note that these beneficial findings have prompted several analyses to clarify the potential application of SGLT2i and initiated large clinical trials in heart failure patients without type 2 diabetes. Of note, there are three large type 2 diabetes cardiovascular outcome trials looking at dapagliflozin, ertugliflozin and sotagliflozin, with results expected over the next four years.

"The favorable effects of SGLT2i ... represent an unexpected bonus of the FDA's advisory in 2008 to test new glucose agents for cardiovascular safety in large post-marketing trials," the authors write. "SGLT2i appears to be effective and relatively safe in patients with type 2 diabetes."

Keywords: Diabetes Mellitus, Type 2, Glucose, Global Health, Glucosides, Benzhydryl Compounds, Myocardial Infarction, Stroke, Hospitalization, Heart Failure, Symporters, Sodium

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