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

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 FAERS database. The reporting odds ratio (ROR) was used as an estimate for detecting AKI signal. A total of 659,573 reports on at least one glucose-lowering drug and/or ARNI were obtained. Of the 413 reports on co-therapy of SGLT2Is and ARNI, 99 (24.0%) reports mentioned AKI. Overall, the AKI reporting rate significantly increased in co-therapy (adjusted ROR, 95%CI:8.04, 6.20-10.42, P<0.001), with a stronger AKI signal in co-therapy of canagliflozin and ARNI (16.82, 3.75-75.57, P<0.001). Specifically, no increased AKI signal was detected in HF cases receiving co-therapy 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 cases 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 co-therapy with SGLT2Is and ARNI. It is necessary to be vigilant that the elderly, patients with diabetes, hypertension or CKD are more susceptible to AKI, especially if they likewise receive diuretics. When co-therapy is unavoidable, early monitoring of renal function, blood volume and blood pressure is excessively crucial. However, it is relatively safe in HF patients.