Sulfonylureas as initial treatment for type 2 diabetes and the risk of adverse cardiovascular events: A population-based cohort study

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 UK'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, ischaemic stroke, cardiovascular death, and all-cause mortality) with sulfonylureas vs 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 myocardial infarction (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 0.85-1.25) but was associated with increased risks of ischaemic stroke (HR: 1.25, 95% CI: 1.002-1.56), cardiovascular death (HR: 1.25, 95% CI: 1.06-1.47), and all-cause mortality (HR: 1.60, 95% CI: 1.45-1.76). This represents an additional 2.0 ischaemic 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 ischaemic stroke, cardiovascular death, and all-cause mortality.