Drug interactions of dipeptidyl peptidase 4 inhibitors involving CYP enzymes and P-gp efflux pump

Abstract

Dipeptidyl peptidase 4 (DPP4) inhibitors are oral antidiabetic drugs approved to manage type 2 diabetes mellitus. Saxagliptin is a substrate of CYP3A4/5 enzymes while other DPP4 inhibitors such as sitagliptin, linagliptin, gemigliptin and teneligliptin are weak substrates of CYP3A4. DPP4 inhibitors have also been identified as substrates of P-gp. Hence, the drugs inhibiting or inducing CYP3A4/5 enzymes and/or P-gp can alter the pharmacokinetics of DPP4 inhibitors. This review is aimed to identify the drugs interacting with DPP4 inhibitors. The plasma concentrations of saxagliptin have been reported to be increased significantly by the concomitant administration of ketoconazole or diltiazem while no significant interactions between various DPP4 inhibitors and drugs like warfarin, digoxin or cyclosporine have been identified.

Keywords: Drug interactions; Sitagliptin; Saxagliptin; Linagliptin; Gemigliptin; Teneligliptin; Vildagliptin; Anagliptin; CYP3A4; P-gp efflux pump

Core tip: The probability of adverse drug interactions is higher among diabetic patients due to the concomitant administration of antidiabetic drugs with multiple medications to treat comorbidities such as hypertension, dyslipidemia, other cardiovascular problems, infections, depression, and others. Dipeptidyl peptidase 4 (DPP4) inhibitors are oral antidiabetic drugs approved to manage type 2 diabetes mellitus. Some of the DPP4 inhibitors have been identified as substrates of CYP3A4/5 enzymes and P-gp efflux pump. The drugs inhibiting or inducing CYP3A4/5 enzymes and/or P-gp can alter the pharmacokinetics of DPP4 inhibitors. The prescribers and the pharmacists are required to be aware of the drugs altering the pharmacokinetics of DPP4 inhibitors significantly to prevent adverse drug interactions.