Sulphonylureas versus metformin and the risk of ventricular arrhythmias among people with type 2 diabetes: A population-based cohort study.

Abstract

To determine whether the use of sulphonylurea monotherapy, compared with metformin monotherapy, is associated with an increased risk of ventricular arrhythmia (VA) among patients initiating pharmacotherapy for type 2 diabetes. We conducted a population-based cohort study using electronic health data extracted from the UK's Clinical Practice Research Datalink Aurum. Using the active comparator, new-user cohort design, we compared rates of VA among patients aged 18 years or older using sulphonylurea monotherapy with those using metformin monotherapy as their initial pharmacological treatment for type 2 diabetes from April 1998 to December 2019. We used a Cox proportional hazards model with inverse probability of treatment weighting by propensity score to estimate the adjusted hazard ratio (aHR) and a corresponding bootstrap 95% confidence interval (CI) for VA with sulphonylurea monotherapy versus metformin monotherapy. The cohort included 92 638 new users of sulphonylurea and 506 882 new users of metformin. A total of 279 VA events occurred among sulphonylurea users (rate per 10 000 person-years: 25.5, 95% CI: 22.7 to 28.7) and 1537 VA events occurred among metformin users (rate per 10 000 person-years: 18.5, 95% CI: 17.6 to 19.5). Compared with metformin, sulphonylureas were associated with an increased risk of VA (aHR: 1.42, 95% CI: 1.18 to 1.69). Sulphonylureas are associated with an increased risk of VA when used as first-line therapy for type 2 diabetes relative to metformin use. This increased risk should be considered when prescribing sulphonylureas as an initial treatment for type 2 diabetes.