Sulfonylureas as Initial Treatment for Type 2 Diabetes and the Risk of Adverse Cardiovascular Events: A Population-based Cohort Study

Kristian B Filion, Antonios Douros, Laurent Azoulay, Hui Yin, Oriana H Yu, Samy Suissa
British Journal of Clinical Pharmacology 2019 July 5

AIMS: Sulfonylureas are recommended as second-line treatment in the management of type 2 diabetes. However, they are still commonly used also as first-line treatment instead of metformin. Given the controversial cardiovascular safety of sulfonylureas, we aimed to determine if their use as first-line treatment is associated with adverse cardiovascular events among patients with newly-treated type 2 diabetes compared with metformin.

METHODS: We conducted a population-based cohort study of patients with newly-treated type 2 diabetes using the United Kingdom's Clinical Practice Research Datalink. Initiators of metformin and sulfonylurea monotherapy were matched on high-dimensional propensity score, and Cox proportional hazards models were used to compare the rate of cardiovascular events (myocardial infarction [MI], ischemic stroke, cardiovascular death, and all-cause mortality) with sulfonylureas versus metformin.

RESULTS: Our cohort included 94,750 patients initiating treatment for type 2 diabetes, 17,612 on a sulfonylurea and 77,138 on metformin. After matching, sulfonylurea monotherapy, compared with metformin monotherapy, was not associated with an increased risk of MI (HR: 1.04, 95% CI: 0.85 to 1.25) but was associated with increased risks of ischemic stroke (HR: 1.25, 95% CI: 1.002 to 1.56), cardiovascular death (HR: 1.25, 95% CI: 1.06 to 1.47), and all-cause mortality (HR: 1.60, 95% CI: 1.45 to 1.76). This represents an additional 2.0 ischemic strokes, 3.5 cardiovascular deaths, and 21.4 all-cause deaths per 1,000 patients per year with sulfonylureas.

CONCLUSIONS: Initiating treatment of type 2 diabetes with a sulfonylurea rather than metformin is associated with higher rates of ischemic stroke, cardiovascular death, and all-cause mortality.

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