Drug Interaction of SGLT2Is and ARNI on Acute Kidney Injury: A Real-World Pharmacovigilance Analysis Through the FAERS.

Abstract: Sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and angiotensin receptor-neprilysin inhibitor (ARNI) may cause potential renal damage, the combined impact of SGLT2Is and ARNI on acute kidney injury (AKI) remains unclear. This pharmacovigilance study conducted a disproportionality analysis using reports from the FDA Adverse Event Reporting System database. The reporting odds ratio was used as an estimate for detecting AKI signal. A total of 659,573 reports on at least 1 glucose-lowering drug and/or ARNI were obtained. Of the 413 reports on cotherapy of SGLT2Is and ARNI, 99 (24.0%) reports mentioned AKI. Overall, the AKI reporting rate significantly increased in cotherapy (adjusted reporting odds ratio, 95% confidence interval: 8.04, 6.20-10.42, P < 0.001), with a stronger AKI signal in cotherapy of canagliflozin and ARNI (16.82, 3.75-75.57, P < 0.001). Specifically, no increased AKI signal was detected in patients with heart failure (HF) receiving cotherapy after adjustment for sex and age (HF: 1.27, 0.89-1.80, P = 0.189; HF plus diabetes: 2.08, 0.99-4.40, P = 0.055; or HF plus hypertension: 1.69, 0.53-5.35, P = 0.376), whereas enhanced AKI signals were detected in patients with diabetes (20.57, 11.93-35.46, P < 0.001), hypertension (4.30, 1.98-9.37, P < 0.001), or diabetes plus hypertension (5.44, 1.92-15.43, P = 0.001). This study reveals that superimposed renal impairment results from cotherapy with SGLT2Is and ARNI. It is necessary to be vigilant that the elderly patients with diabetes, hypertension, or chronic kidney disease are more susceptible to AKI, especially if they likewise receive diuretics. When cotherapy is unavoidable, early monitoring of renal function, blood volume, and blood pressure is excessively crucial. However, it is relatively safe in patients with HF.