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Sulfonylureas increased risk for CVD events, death
Using sulfonylureas as initial therapy for type 2 diabetes vs. metformin increased the risk for cardiovascular events and death by 21%, according to data from a retrospective cohort study.
“This translates into an excess of approximately 2.2 (95% CI, 1.4-3.0) cardiovascular events or deaths per 1,000 person-years of sulfonylurea use,” researchers wrote.
However, they said, “The findings do not clarify whether the difference in CVD risk is due to harm from sulfonylureas, benefit from metformin, or both.”
Using data sets from national Veterans Health Administration (VHA) Decision-Support Services, researchers identified veterans aged at least 18 years who started oral monotherapy for diabetes from October 2001 to September 2008.
Follow-up ranged from prescription date to the first of the following: a switch to or addition of another antidiabetic drug; the 90th day with no drugs in hand; an outcome; or a censoring event, researchers wrote. Censoring events were defined as serum creatinine levels of at least 133 mcmol/L, the 181st day of no contact with any VHA facility or the end of the study.
The primary endpoint was hospitalization for acute myocardial infarction or stroke, or death. Researchers adjusted for baseline demographics; cholesterol, HbA1c and serum creatinine levels; blood pressure; BMI; health care utilization and comorbid conditions.
Treatment was initiated among 253,690 patients: 98,665 starting sulfonylureas and 155,025 starting metformin.
According to researchers, crude rates of the composite outcome were 18.2 per 1,000 person-years for sulfonylurea users and 10.4 per 1,000 person-years for those taking metformin (adjusted incidence rate difference=2.2; 95% CI, 1.4-3.0). More CVD rates occurred per 1,000 person-years among sulfonylurea users vs. metformin (HR=1.21; 95% CI, 1.13-1.30).
Results remained consistent for glyburide (HR=1.26; 95% CI, 1.16-1.37) and glipizide (HR=1.15; 95% CI, 1.06-1.26) throughout the study, including subgroups by CVD history, age, BMI and albuminuria; a propensity score-matched cohort analysis; and sensitivity analyses.
Researchers noted limitations, including that most veterans included in the study were white men. Although data on women and minority groups were limited, they were reflective of the VHA population, they added.
“These observations support the use of metformin for first-line diabetes therapy and strengthen the evidence about the cardiovascular advantages of metformin compared with sulfonylureas,” they wrote.
According to Steven E. Nissen, MD, author of an accompanying editorial, findings by Roumie and colleagues have implications for millions of patients with diabetes worldwide.
“Despite the recognized limitations of observational studies, the findings are credible and important. Sulfonylureas seem inferior to metformin with respect to CV outcomes. However, in the absence of a modern RCT confirming the findings, we must view these data as ‘hypothesis-generating’ rather than definitive,” he wrote.
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