Sulfonylureas Associated With Increased Risk of Death

Three members of the sulfonylurea class of diabetes drugs are associated with a significantly increased risk of death compared with metformin, a study has found.

Several members of a widely used class of diabetes drugs called sulfonylureas are associated with a significantly increased risk of death compared with metformin, another widely used diabetes drug, according to the results of a study presented on June 25, 2012, at the annual meeting of the Endocrine Society in Houston.

The goal of the study was to assess the risk of overall mortality in patients with type 2 diabetes who were treated with the sulfonylureas glipizide, glyburide, or glimepiride compared with metformin. The researchers conducted a retrospective cohort study using electronic health records from the Cleveland Clinic. They found 23,915 adult patients with type 2 diabetes with and without coronary artery disease (CAD) who started monotherapy with metformin (12,774 participants), glipizide (4325 participants), glyburide (4279 participants), or glimepiride (2537 participants).

The average follow-up time for the entire cohort was 2.2 years. Among the entire cohort, there were a total of 2546 deaths in 58,513 person-years of follow-up, and in the subgroup that had CAD, there were 419 deaths in 5980 person-years of follow-up. In the entire cohort, compared with metformin, glipizide was associated with a 64% increased risk of death, glyburide was associated with a 59% increased risk of death, and glimepiride was associated with a 68% increased risk of death. In the subgroup of participants that had CAD, glimepiride was not associated with a significantly increased risk of death compared with metformin, but glipizide was associated with a 41% increased risk of death, and glyburide was associated with a 38% increased risk of death.

“We have clearly demonstrated that metformin is associated with a substantial reduction in mortality risk, and, thus, should be the preferred first-line agent, if one has a choice between metformin and a sulfonylurea,” said lead study author Kevin M. Pantalone, DO, an endocrinologist at Summa Western Reserve Hospital in Cuyahoga Falls, OH, in a press release.