November 14, 2012
Diabetics Starting With Sulfonylureas Had
More Cardiac Events

Nashville—Patients who received sulfonylureas as first-line treatment for diabetes suffered a higher rate of cardiovascular events and death than those initiating treatment with metformin, according to a new study of veterans.

Researchers from the U.S. Department of Veterans Affairs and Vanderbilt University reviewed data on 253,690 veterans beginning diabetes treatment to compare the effects of therapy selection on cardiovascular disease outcomes or death.

In the study, published recently in the Annals Internal Medicine, 98,665 patients began treatment with sulfonylureas, while 155,025 started with metformin. Researchers found that sulfonylurea use was associated with a 21% increased risk of acute myocardial infarction, stroke or death.

In 2007, more than 10.1 million Americans (approximately 34% of patients with treated diabetes) used a sulfonylurea as part of their diabetes treatment, according to the study.

“The reason for the difference in risk between metformin and sulfonylurea users remains unknown,” according to the researchers who say they could not conclude whether sulfonylureas themselves are harmful, or if metformin is protective. They also could not determine if differences in patient characteristics contributed to varying rates of cardiovascular events and death.

“Compared with metformin, sulfonylureas are associated with increases in weight and lipid levels and greater risk for hypoglycemia but similar glycemic control,” the authors write. ”Thus, metformin is recommended as first-line therapy for patients without contraindications. Nonetheless, sulfonylureas are sometimes preferred because they require little titration and have fewer gastrointestinal adverse effects than metformin.”

Steven E. Nissen, MD, a cardiologist from the Cleveland Clinic, called the findings “credible and important” in an accompanying editorial.

“How might sulfonylureas increase adverse CV outcomes? One theory focuses on their adverse effects on ischemic preconditioning, an adaptive mechanism that allows the myocardium to resist necrosis after intermittent periods of ischemia,” Nissen writes. “Another hypothesis relates to sulfonylurea-induced hypoglycemia, which theoretically may result in myocardial ischemia.”

“Regardless of mechanism, this scientific question demands a definitive answer,” he adds. “In the absence of an industry-sponsored study, public health authorities should conduct such a clinical trial. With more than two thirds of diabetic patients dying of CV causes and millions of patients currently receiving sulfonylureas, this question must be resolved with high-quality evidence.”

U.S. Pharmacist Social Connect