Risk of sudden cardiac arrest and ventricular arrhythmia with sulfonylureas: An experience with conceptual replication in two independent populations

Sulfonylureas are commonly used to treat type 2 diabetes mellitus. Despite awareness of their effects on cardiac physiology, a knowledge gap exists regarding their effects on cardiovascular events in real-world populations. Prior studies reported sulfonylurea-associated cardiovascular death but not serious arrhythmogenic endpoints like sudden cardiac arrest (SCA) or ventricular arrhythmia (VA). We assessed the comparative real-world risk of SCA/VA among users of second-generation sulfonylureas: glimepiride, glyburide, and glipizide. We conducted two incident user cohort studies using five-state Medicaid claims (1999–2012) and Optum Clinformatics commercial claims (2000–2016). Outcomes were SCA/VA events precipitating hospital presentation. We used Cox proportional hazards models, adjusted for high-dimensional propensity scores, to generate adjusted hazard ratios (aHR). We identified 624,406 and 491,940 sulfonylurea users, and 714 and 385 SCA/VA events, in Medicaid and Optum, respectively. Dataset-specific associations with SCA/VA for both glimepiride and glyburide (vs. glipizide) were on opposite sides of and could not exclude the null (glimepiride: aHRMedicaid 1.17, 95% CI 0.96–1.42; aHROptum 0.84, 0.65–1.08; glyburide: aHRMedicaid 0.87, 0.74–1.03; aHROptum 1.11, 0.86–1.42). Database differences in data availability, populations, and documentation completeness may have contributed to the incongruous results. Emphasis should be placed on assessing potential causes of discrepancies between conflicting studies evaluating the same research question.