Investigating Sodium-Glucose Cotransporter 2 Inhibitors Versus Other Glucose-Lowering Drugs on Ventricular Arrhythmias or Sudden Cardiac Death Using the US FDA Adverse Event Reporting System.

Abstract

Purpose: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reported to exhibit antiarrhythmic effects. However, there is conflicting evidence regarding the association between SGLT2 inhibitors and ventricular arrhythmias or sudden cardiac death (SCD). We utilized the US FDA Adverse Event Reporting System (FAERS) database to investigate the reporting frequencies of SGLT2 inhibitors with ventricular arrhythmias and SCD compared to other glucose-lowering drugs (ATC-A10B).

Methods: We used the web data mining tool AERSMine to mine reports of ventricular arrhythmias and SCD from FAERS to compare SGLT2 inhibitors versus other glucose-lowering drugs. The mining range was from 2004q1 to 2023q3. Disproportionality analysis used the proportional reporting ratio (PRR) with 95% confidence interval (CI) and information component (IC) with 95% credible interval.

Results: From 2004q1 to 2023q3, a total of 121,129 adverse events were reported for SGLT2 inhibitors, with a total of 1,127,485 in the ATC-A10B group. Ventricular arrhythmias reporting frequency in the SGLT2 inhibitors group was similar to that of the control group (1.36/1000 reports vs 1.55/1000 reports; p = 0.10), with a PRR of 0.88 (95%CI 0.75-1.03). However, the reporting frequency of SCD in the SGLT2 inhibitors group was significantly lower than that of the control group (1.43 vs 4.70/1000; p < 0.001), with a PRR of 0.30 (95%CI 0.26-0.35), and this trend was observed within individual molecules of SGLT2 inhibitors. During the sensitivity analysis process, the results obtained when restricting the scope of data mining to between 2013q1 and 2023q3 were similar to those obtained when using data from 2004q1 to 2023q3.

Conclusion: In this drug pharmacovigilance assessment, the reporting frequency of ventricular arrhythmias associated with SGLT2 inhibitors was similar to that of other antidiabetic medications, while the reporting frequency of SCD related to SGLT2 inhibitors was lower. This real-world study evidence complements existing clinical evidence.