Abstract
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.
Highlights
Sulfonylureas are commonly used to treat type 2 diabetes mellitus
This study examined the comparative risk of sudden cardiac arrest (SCA)/ventricular arrhythmia (VA) among users of individual second-generation sulfonylureas in two independent United States (US) populations
The crude incidence rates of SCA/VA in the Medicaid (3.55 per 1,000 p-y) and Optum (1.95 per 1,000 p-y) populations are similar to those reported in other diabetic populations[26,27] and higher than those reported in general populations[27,28], potentially explained by the two to fourfold increase in risk of SCA with diabetes[26,29]
Summary
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. Conceptual replication can be challenging because of inherent differences in populations under study and/or databases used; data source choice can substantively affect results of nonexperimental population-based studies[19] While examples of both randomized and nonrandomized studies with the same research question but conflicting results abound[20,21,22,23,24], few have assessed probable causes of their inconsistencies. We evaluated the same clinical question in independent populations of second-generation sulfonylurea users, compared this to our prior results on the topic[25], and explored potential reasons for similarities and differences among findings
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