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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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

Plain Language Summary

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are used for the management of heart failure with preserved ejection fraction (HFpEF). It is important to assess their comparative risk of urinary tract infection (UTI) or genital infection among patients with HFpEF. We compared patients with HFpEF using SGLT2i in three pairwise groups: cohort 1, dapagliflozin versus canagliflozin; cohort 2, empagliflozin versus canagliflozin; and cohort 3, dapagliflozin versus empagliflozin. We found that there was no significant difference in the risk of genitourinary infections including UTI or genital infections among dapagliflozin, empagliflozin, and canagliflozin.

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Funding

No funding was received to conduct this study.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, 1889 Museum Road, Gainesville, FL, 32611, USA

    Munaza Riaz, **gchuan Guo, Steven M. Smith & Haesuk Park

  2. Division of Cardiovascular Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA

    Steven M. Smith & David E. Winchester

  3. Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA

    Eric A. Dietrich

Authors
  1. Munaza Riaz
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  2. **gchuan Guo
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  3. Steven M. Smith
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  4. Eric A. Dietrich
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  5. David E. Winchester
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  6. Haesuk Park
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Corresponding author

Correspondence to Haesuk Park.

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Ethics Statement

This study was approved by the University of Florida Institutional Review Board and used de-identified data from administrative claims databases.

Conflict of Interest

Munaza Riaz, **gchuan Guo, Steven M. Smith, Eric A. Dietrich, David E. Winchester, and Haesuk Park declare that they have no potential conflicts of interest that might be relevant to the contents of this article.

Author Contributions

The study was conceptualized by MR. All the authors designed the methodology of the study. MR analyzed the data and drafted the first version of the manuscript. All authors reviewed the manuscript and read and approved the final version.

Data Availability Statement

This study utilized MarketScan® data under a licensed agreement, which restricts the authors from sharing the data. Individuals seeking access to the data should contact the provider directly.

Code Availability

Not applicable.

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Not applicable.

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Not applicable.

Supplementary Information

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Supplementary file1 (DOCX 449 KB)

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Riaz, M., Guo, J., Smith, S.M. et al. Comparative Genitourinary Safety of In-class Sodium-Glucose Cotransporter-2 Inhibitors among Patients with Heart Failure with Preserved Ejection Fraction: A Cohort Study. Am J Cardiovasc Drugs 24, 455–464 (2024). https://doi.org/10.1007/s40256-024-00648-2

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