Association between dipeptidyl peptidase-4 inhibitors and acute kidney injury in patients with diabetes mellitus: A disproportionality analysis based on the US Food and Drug Administration Adverse Event Reporting System

Purpose Although dipeptidyl peptidase-4 inhibitors (DPP-4Is) are widely used in the treatment of diabetes—a known risk factor for renal function decline—the potential association between DPP-4Is and acute kidney injury (AKI) remains controversial. This study aimed to evaluate the association between DPP-4Is and AKI while considering the concomitant use of AKI inducers in patients with diabetes. Methods Data from the US Food and Drug Administration Adverse Event Reporting System were analyzed, focusing on seven DPP-4Is. Disproportionality analysis was performed to determine the association between DPP-4Is and AKI using reporting odds ratios and information components, stratified by age groups, in the presence or absence of 10 types of AKI inducers used concomitantly. Results Of 215,051 reports, a positive association between DPP-4Is and AKI was found for linagliptin, sitagliptin, and vildagliptin in the overall analysis. Age-stratified analysis revealed associations between four DPP-4Is and AKI in the middle-aged group, whereas only sitagliptin and vildagliptin were associated with AKI in the elderly group. Exclusion of concomitant renin-angiotensin-aldosterone system inhibitors, diuretics, or NSAIDs altered signal detection for certain DPP-4Is, with these changes varying by age group. Conclusion This study suggests that some DPP-4Is, including linagliptin, sitagliptin, and vildagliptin, are associated with AKI, even without concomitant use of AKI inducers. Given the widespread use of DPP-4Is and the severity of AKI, clinicians should be sufficiently informed about their potential relationship.