Association Between Dipeptidyl Peptidase-4 Inhibitor Use and Acute Kidney Injury in Patients With Diabetes Mellitus:...

Although dipeptidyl peptidase-4 inhibitors (DPP4is) are widely used in the treatment of diabetes, a known risk factor for renal function decline, the potential association between DPP4i use and acute kidney injury (AKI) remains controversial. This study aimed to evaluate the association between DPP4i and AKI while considering the concomitant use of inducers of AKI in patients with diabetes.

Data from the US Food and Drug Administration Adverse Event Reporting System were analyzed, focusing on seven DPP4is in daily use, namely alogliptin, anagliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin. Disproportionality analysis was performed to determine the association between DPP4i use and AKI using reporting odds ratios and information components, stratified by age groups, in the presence or absence of 10 types of AKI inducer used concomitantly.

Of 215,051 reports, a positive association between DPP4i and AKI was found for linagliptin, sitagliptin, and vildagliptin in the overall analysis. Age-stratified analysis revealed associations between the DPP4is linagliptin, saxagliptin, sitagliptin and vildagliptin and AKI in the middle-aged group of patients, whereas only sitagliptin and vildagliptin were associated with AKI in the elderly group. Exclusion of concomitant renin-angiotensin-aldosterone system inhibitors, diuretics, or non-steroidal anti-inflammatory drugs altered signal detection for certain DPP4is, with these changes varying by age group.

This study suggests that some DPP4is, including linagliptin, sitagliptin and vildagliptin, are associated with AKI, even without concomitant use of an AKI inducer. Given the widespread use of DPP4is and the severity of AKI, clinicians should be sufficiently informed about their potential relationship.