Sulfonylureas associated with higher CV risk than metformin

As initial monotherapy for type 2 diabetes, sulfonylureas were associated with more cardiovascular events and deaths than metformin, a new study found.

The retrospective cohort study included about 250,000 patients of the Veterans Health Administration who initiated oral therapy for diabetes and who did not have chronic kidney disease (serum creatinine of 1.5 mg/dl or greater) or other serious medical illness. About 150,000 of them took metformin and 99,000 took a sulfonylurea. The groups were compared on a composite outcome of death or hospitalization for acute myocardial infarction or stroke.

Results appeared in Annals of Internal Medicine on Nov. 6.

Sulfonylurea users had 18.2 composite events per 1,000 person-years compared to 10.4 per 1,000 person-years among metformin users (adjusted incidence rate difference, 2.2 [95% CI, 1.4 to 3.0]; adjusted hazard ratio, 1.21 [95% CI, 1.13 to 1.30]). The results were consistent when the researchers assessed subgroups by sulfonylurea type (glyburide or glipizide), cardiovascular disease history, age, body mass index, albuminuria and propensity score.

The study suggests that sulfonylureas are associated with an increased risk of cardiovascular disease events and death compared to metformin, and it supports the use of metformin as first-line therapy, the study authors concluded. They cautioned that the study is limited by its mostly white male population and that confounding by indication is a risk. It's also still unknown whether the difference in outcomes results from more harm from sulfonylureas or greater benefit from metformin. Sulfonylureas are associated with increases in weight, lipid levels and hypoglycemia compared to metformin, the authors noted.

Cardiovascular risks have been a concern with sulfonylureas for a long time, noted both the study and an accompanying editorial. A study in 1970 showed increased risk of all-cause and cardiovascular mortality with tolbutamide, but randomized trials comparing cardiovascular outcomes of diabetes drugs have been avoided since then, the editorialist said. This nonrandomized study should be considered hypothesis-generating rather than definitive, but the findings are creditable, important and have implications for millions of patients, according to the editorial.