Higher daily doses of glyburide (HR 1.3) and first-generation sulfonylureas (HR 2.1) were associated with an increased risk of all-cause mortality compared to lower doses in patients with type 2 diabetes.
Cohort (n=5,795)
Does higher exposure to sulfonylureas increase mortality in patients newly treated for type 2 diabetes?
Higher exposure to sulfonylureas, but not metformin, is associated with increased mortality in patients newly treated for type 2 diabetes, suggesting the mechanism of glucose lowering impacts cardiovascular outcomes.
Effect estimate: HR 1.3 (95% CI 1.2-1.4)
Background: Over the past 30 years, the relation between use of sulfonylureas to treat type 2 diabetes and the risk of cardiovascular events has been vigorously debated. The purpose of this study was to determine if the risk of death changes with level of exposure to sulfonylurea drugs. Methods: This was a retrospective, inception cohort study using administrative data from Saskatchewan Health (1991– 1999). The 5795 subjects, identified by their first-ever dispensation for an oral antidiabetic agent, were grouped according to their use of such agents during follow-up. Potential subjects using insulin or combination therapy were excluded. Exposure level was defined by daily dose and degree of adherence. Separate multivariate Cox proportional-hazard models were constructed for each monotherapy group and used to calculate the risk of death associated with higher versus lower exposure category. Disease severity indicators were identified among the administrative data and entered as covariates in each model. The main outcomes were all-cause mortality and death from an acute ischemic event. Results: The mean age of the cohort members was 66.3 (standard deviation SD 13.4) years; 43.4% were female; and their mean duration of follow-up was 4.6 (SD 2.1) years. First-generation sulfonylureas were used exclusively by 120 subjects; glyburide, by 4138; and metformin, by 1537. A greater risk of death was associated with higher daily doses of the first-generation sulfonylureas (adjusted hazard ratio HR 2.1, 95% confidence interval CI 1.0–4.7) and glyburide (HR 1.3, 95% CI 1.2–1.4), but not metformin (HR 0.8, 95% CI 0.7–1.1). Similar associations were observed for death caused by an acute ischemic event. Interpretation: Higher exposure to sulfonylureas was associated with increased mortality among patients newly treated for type 2 diabetes. The same relation was not observed with metformin. This implies that the manner in which blood glucose concentration is lowered may be as important as achieving recommended glucose targets.
Scot H. Simpson (Mon,) conducted a cohort in Type 2 diabetes mellitus (n=5,795). Glyburide vs. Lower daily dose (below median) was evaluated on All-cause mortality (HR 1.3, 95% CI 1.2-1.4). Higher daily doses of glyburide (HR 1.3) and first-generation sulfonylureas (HR 2.1) were associated with an increased risk of all-cause mortality compared to lower doses in patients with type 2 diabetes.
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