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World J Diabetes. Feb 15, 2022; 13(2): 85-96
Published online Feb 15, 2022. doi: 10.4239/wjd.v13.i2.85
Role of dipeptidyl peptidase 4 inhibitors in the new era of antidiabetic treatment
Matilda Florentin, Michael S Kostapanos, Athanasia K Papazafiropoulou
Matilda Florentin, Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina 45221, Greece
Michael S Kostapanos, Lipid Clinic, Department of General Medicine, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom
Athanasia K Papazafiropoulou, 1st Department of Internal Medicine and Diabetes Center, Tzaneio General Hospital of Piraeus, Athens 18536, Greece
Author contributions: All authors contributed equally to writing the manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
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 NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Athanasia K Papazafiropoulou, MD, MSc, PhD, Consultant Physician-Scientist, 1st Department of Internal Medicine and Diabetes Center, Tzaneio General Hospital of Piraeus, Leoforos Afentouli, Athens 18536, Greece. athpapazafiropoulou@gmail.com
Received: May 5, 2021
Peer-review started: May 5, 2021
First decision: June 16, 2021
Revised: July 29, 2021
Accepted: January 27, 2022
Article in press: January 27, 2022
Published online: February 15, 2022
Abstract

The last few years important changes have occurred in the field of diabetes treatment. The priority in the therapy of patients with diabetes is not glycemic control per se rather an overall management of risk factors, while individualization of glycemic target is suggested. Furthermore, regulatory authorities now require evidence of cardiovascular (CV) safety in order to approve new antidiabetic agents. The most novel drug classes, i.e., sodium-glucose transporter 2 inhibitors (SGLT2-i) and some glucagon-like peptide-1 receptor agonists (GLP-1 RA), have been demonstrated to reduce major adverse CV events and, thus, have a prominent position in the therapeutic algorithm of hyperglycemia. In this context, the role of previously used hypoglycemic agents, including dipeptidyl peptidase 4 (DPP-4) inhibitors, has been modified. DPP-4 inhibitors have a favorable safety profile, do not cause hypoglycemia or weight gain and do not require dose uptitration. Furthermore, they can be administered in patients with chronic kidney disease after dose modification and elderly patients with diabetes. Still, though, they have been undermined to a third line therapeutic choice as they have not been shown to reduce CV events as is the case with SGLT2-i and GLP-1 RA. Overall, DPP-4 inhibitors appear to have a place in the management of patients with diabetes as a safe class of oral glucose lowering agents with great experience in their use.

Keywords: Cardiovascular safety, Dipeptidyl peptidase 4 inhibitors, Glucose lowering, Hypoglycemia, Therapeutic algorithm, Weight gain

Core Tip: Dipeptidyl peptidase 4 inhibitors have a favorable safety profile, do not frequently cause hypoglycemia and weight gain, while they may be used in patients with kidney impairment and the elderly. Despite not reducing cardiovascular events, they still have a place in the diabetes treatment algorithm in several patients.