Second-Line Sulfonylureas Increase Risks in Type 2 Diabetes

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Sulfonylureas are widely used as second-line oral antidiabetic therapy, despite potential cardiotoxicity and hypoglycemia risk. A new UK population-based cohort study suggests that such second-line treatment with sulfonylureas is associated with increased risks of myocardial infarction, death, and severe hypoglycemia. The study was published in the British Medical Journal.

Using the UK Clinical Practice Research Datalink, the researchers identified 77,138 patients with type 2 diabetes who started metformin monotherapy between 1998 and 2013. In a prevalent new-user design, the analysis included 23,592 patients who added or switched to sulfonylurea as second-line therapy and the same number of patients who remained on metformin.

The two groups were matched for high-dimensional propensity score, hemoglobin A1c, and number of previous metformin prescriptions. The two groups were compared for risk of myocardial infarction, ischemic stroke, death from cardiovascular causes, death from any cause, or severe hypoglycemia.

At a mean follow-up of 1.1 years, sulfonylurea therapy was associated with significant increases in myocardial infarction, hazard ratio (HR) 1.26; all-cause mortality, HR 1.15; and severe hypoglycemia, HR 7.60. There were also trends toward increased risk of ischemic stroke and cardiovascular death in patients receiving second-line sulfonylureas. Compared to patients who added sulfonylureas, those who switched to sulfonylureas were at increased risk of myocardial infarction, HR 1.51; and all-cause mortality, HR 1.51.

Compared to metformin, second-line sulfonylurea therapy for type 2 diabetes was found to be associated with an increased risk of cardiovascular and hypoglycemic events, the authors said.

“Continuing metformin when introducing sulfonylureas appears to be safer than switching,” the researchers write [Douros A, et al. Sulfonylureas as second line drugs in type 2 diabetes and the risk of cardiovascular and hypoglycaemic events: population based cohort study. BMJ 2018; 362: k2693.