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Acute kidney injury following SGLT2 inhibitors among diabetic patients: a pharmacovigilance study

  • Nephrology - Original Paper
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International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

The sodium–glucose cotransporter-2 (SGLT2) inhibitors have changed the treatment of type 2 diabetes mellitus. Several studies evaluated SGLT2 inhibitor-related acute kidney injury (AKI), but pharmacoepidemiology studies are needed to compare the adverse events in different SGLT2 inhibitors (SGLT2i).

Methods

We used disproportionality analysis and Bayesian analysis in data mining to screen the AKI cases after initiating different SGLT2i among diabetic patients, based on the FDA’s Adverse Event Reporting System (FAERS) updated to December 2020. We also investigated the onset time and fatality rates of SGLT2i-associated AKI, which was based on preferred terms (PTs) coded for the renal adverse events in the structure of the FARES database.

Results

We identified 2483 cases of AKI following SGLT2i regimens among diabetic patients. Most of them were 45–64 years old (58.46%) and > 65 years old (28.67%). Canagliflozin generated the largest number of AKI reports (n = 1650, 66.45%) in our study. Canagliflozin showed the strongest association among SGLT2i, evidenced by the highest reporting odds ratio (ROR = 3.70, two-sided 95% CI 3.51–3.91), proportional reporting ratio (PRR = 3.39, χ2 = 2635.06), and empirical Bayes geometric mean (EBGM = 3.18, one-sided 95% CI 3.04). The median onset time to AKI was 72.0 (interquartile range [IQR] 21.0–266.0) days after SGLT2i initiation. The general hospitalization rate of SGLT2i-associated AKI was 63.50%, and the fatality rate was 1.59%. The deceased patients (62.94 ± 10.69 years) were significantly older than the survived ones (57.82 ± 11.84 years) (P = 0.011).

Conclusion

We compared AKI events in the real-world practice of various SGLT2i among diabetic cases from the FAERS database. It is essential to monitor kidney function during the early administration of SGLT2i. Concern should be paid for AKI in patients older than 65 taking SGLT2i.

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Availability of data and materials

All necessary data have been presented as tables and figures in the manuscript. Related information is accessible under request to the corresponding author.

Abbreviations

AKI:

Acute kidney injury

SGLT2:

Sodium–glucose cotransporter-2

SGLT2i:

SGLT2 inhibitor

AE:

Adverse event

FAERS:

The Food and Drug Administration’s Adverse Event Reporting System

ROR:

Reporting odds ratio

PRR:

Proportional reporting ratio

EBGM:

Empirical Bayes geometric mean

IQR:

Interquartile range

FDA:

The Food and Drug Administration

SRS:

Spontaneous reporting system

BCPNN:

Bayesian confidence propagation neural network

MGPS:

Multi-item gamma Poisson shrinker

RAS:

Renin–angiotensin system

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Acknowledgements

This work has been made possible through an ISN Sister Renal Centers Grant.

Funding

This study was supported by Thrombocytopenia Funding from Yeehong School of Shenyang Pharmaceutical University (TCP funding).

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Author notes

  1. Gang Chen and Xiaolin Li have contributed equally to this manuscript.

Authors and Affiliations

  1. Nephrology Department, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

    Gang Chen, Quexuan Cui, Yangzhong Zhou &  Xuemei

  2. Pharmacy Department, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100730, China

    Xiaolin Li, Bin Zhao & Dan Mei

  3. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

    Xiaolin Li

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  1. Gang Chen
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Contributions

GC designed the study, analyzed and interpreted data, generated figures/tables, and drafted the manuscript. XL analyzed and interpreted data, and drafted the manuscript. QC contributed to manuscript drafting. BZ designed the study and directed the data mining in the FAERS database. QC, YZ, DM, and XL reviewed and corrected the manuscript.

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Correspondence to Bin Zhao.

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Chen, G., Li, X., Cui, Q. et al. Acute kidney injury following SGLT2 inhibitors among diabetic patients: a pharmacovigilance study. Int Urol Nephrol 54, 2949–2957 (2022). https://doi.org/10.1007/s11255-022-03211-7

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