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World J Meta-Anal. Apr 30, 2019; 7(4): 156-161
Published online Apr 30, 2019. doi: 10.13105/wjma.v7.i4.156
Drug interactions of dipeptidyl peptidase 4 inhibitors involving CYP enzymes and P-gp efflux pump
Naina Mohamed Pakkir Maideen
Naina Mohamed Pakkir Maideen, Department of Pharmacy, Dubai Health Authority, Dubai 4545, United Arab Emirates
Author contributions: Maideen NMP solely contributed to this article.
Conflict-of-interest statement: There is no conflict of interest for this review.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Naina Mohamed Pakkir Maideen, PhD, Doctor, Pharmacist, Pharmacologist, Department of Pharmacy, Dubai Health Authority, Al Maktoum Bridge Street, Dubai 4545, United Arab Emirates. nmmaideen@dha.gov.ae
Telephone: +971-42-164952 Fax: +971-42-244302
Received: March 18, 2019
Peer-review started: March 18, 2019
First decision: April 13, 2019
Revised: April 21, 2019
Accepted: April 23, 2019
Article in press: April 23, 2019
Published online: April 30, 2019
Processing time: 43 Days and 20 Hours
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.