Comparative Genitourinary Safety of In-class Sodium-Glucose Cotransporter-2 Inhibitors among Patients with Heart Failure with Preserved Ejection Fraction: A Cohort Study

The American Heart Association recommended sodium-glucose cotransporter-2 inhibitors (SGLT2i) for the management of heart failure with preserved ejection fraction (HFpEF). However, little is known about their real-world in-class comparative safety in patients with HFpEF. We aimed to assess the comparative safety of SGLT2i in the risk of urinary tract infection (UTI) or genital infection separately or as a composite outcome among patients with HFpEF.

This cohort study using MarketScan^® Commercial and Medicare supplemental databases (2012–2020) included patients aged ≥ 18 years with a diagnosis of HFpEF who initiated SGLT2i therapy. Three pairwise comparison groups were established: cohort 1, dapagliflozin versus canagliflozin; cohort 2, empagliflozin versus canagliflozin; and cohort 3, dapagliflozin versus empagliflozin. After stabilized inverse probability treatment weighting, Cox proportional hazards regression was used to compare the risk of UTI or genital infection separately or as a composite outcome in each cohort.

The risk of the composite outcome did not significantly differ between canagliflozin and dapagliflozin (adjusted hazard ratio [aHR] 0.64; 95% confidence interval [CI] 0.36–1.14) or between empagliflozin and canagliflozin (aHR 1.25; 95% CI 0.77–2.05). Similarly, there was no evidence of difference between dapagliflozin and empagliflozin in this risk (aHR 0.76; 95% CI 0.48–1.21). The results of analyses separately assessing UTI or genital infection were similar.

There was no significant difference in the risk of UTI or genital infection among patients with HFpEF who initiated canagliflozin, dapagliflozin, or empagliflozin.