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Correlations Between SGLT-2 Inhibitors and Acute Renal Failure by Signal Detection Using FAERS: Stratified Analysis for Reporting Country and Concomitant Drugs

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Abstract

Background

Previous studies have shown conflicting observations regarding the correlation between sodium-glucose-cotransporter-2 inhibitors (SGLT2i) and acute renal failure. Although wide use has contributed to the accumulation of safety information on SGLT2i, the examination of the countries reporting cases of SGLT2i use and influence of concomitant drugs has been insufficient in studies using spontaneous adverse event reporting databases.

Objective

We aimed to re-examine the correlation between SGLT2i and acute renal failure using the latest United States Food and Drug Administration’s Adverse Event Reporting System (FAERS) records and to conduct a stratified analysis for the reporting countries (Japan or other countries), as well as the concomitant use of drugs such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) with SGLT2i.

Patients and Methods

The reporting odds ratio (ROR) and 95% confidence interval (CI) for cases recorded on FAERS from January 2013 to March 2020 were calculated. We then limited the cases to patients using SGLT2i and receiving treatment for diabetes mellitus and then calculated the ROR. A stratified analysis was performed for reporting countries (Japan or other countries), and the presence or absence of concomitant use of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) to examine their influence on the correlation between SGLT2i and acute renal failure.

Results

Of the 5,337,069 cases of adverse events recorded on FAERS, 410,569 were cases in which patients had received treatment for diabetes. The ROR for SGLT2i calculated from the total analysis subjects was 4.16 (95% CI 4.01–4.31), suggesting its correlation with acute renal failure. Similar results were obtained for the cases in which patients had received treatment for diabetes. However, the stratified analysis of these diabetes-treatment cases for reporting countries showed no correlation between SGLT2i and acute renal failure in cases reported in Japan with ROR 0.58 (95% CI 0.49–0.69). In contrast, a correlation was suggested in cases reported in countries other than Japan with ROR 1.91 (95% CI 1.83–1.98). Moreover, the stratified analysis for the concomitant use of an ACEi or ARB showed that the ROR tended to be low in the cases with one of these drugs.

Conclusion

Examination with the signal detection method using FAERS suggested the correlation between SGLT2i and the onset of acute renal failure. However, when focusing on the cases reported in Japan, such a correlation was not suggested. In addition, this study indicated that the signal of acute renal failure tends to be reduced in cases with the concomitant use of either an ACEi or ARB. Through this study we suggest that patients should be closely monitored when they take SGLT2i without an ACEi or ARB.

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Authors and Affiliations

  1. International University of Health and Welfare Graduate School Graduate School of Health and Welfare Sciences, 4-1-26 Akasaka, Minato-city, Tokyo, 107-8402, Japan

    Yukari Katsuhara & Shunya Ikeda

Authors
  1. Yukari Katsuhara
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  2. Shunya Ikeda
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Corresponding author

Correspondence to Yukari Katsuhara.

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Funding

The authors received no specific funding for this study.

Conflict of interest

Yukari Katsuhara is an employee of Takeda Pharmaceutical Company Limited and had been on leave during the research period. Shunya Ikeda has no conflict of interest.

Ethics approval

This study used anonymized information from the database, which is open to the public; therefore, in accordance with the 1964 Helsinki Declaration (and its amendments), institutional ethics approval was not required.

Consent to participate

This study used anonymized information from the database, which is open to the public; therefore, in accordance with the 1964 Helsinki Declaration (and its amendments), institutional ethics approval was not required.

Consent for publication

Not applicable.

Availability of data and material

The datasets analyzed in this study are available in the FDA Adverse Event Reporting System (FAERS): https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-latest-quarterly-data-files

Code availability

Not applicable.

Authors contributions

Both authors were investigators in the study and participated in the study design, interpretation of the study results, and in the drafting, critical revision, and approval of the final version of the manuscript.

Acknowledgements

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Supplementary Information

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Katsuhara, Y., Ikeda, S. Correlations Between SGLT-2 Inhibitors and Acute Renal Failure by Signal Detection Using FAERS: Stratified Analysis for Reporting Country and Concomitant Drugs. Clin Drug Investig 41, 235–243 (2021). https://doi.org/10.1007/s40261-021-01006-9

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