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

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, chi(2) = 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.