Letter to the Editor
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 15, 2022; 13(6): 466-470
Published online Jun 15, 2022. doi: 10.4239/wjd.v13.i6.466
Relook at DPP-4 inhibitors in the era of SGLT-2 inhibitors
Awadhesh Kumar Singh, Ritu Singh
Awadhesh Kumar Singh, Ritu Singh, Department of Diabetes & Endocrinology, G.D Hospital & Diabetes Institute, Kolkata 700013, West Bengal, India
Author contributions: Singh AK designed the research; Singh R performed the research, Singh AK and Singh R analyzed the data; Singh AK wrote the letter, and Singh R revised the manuscript.
Conflict-of-interest statement: The authors have nothing to disclose.
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: Awadhesh Kumar Singh, MBBS, MD, DM, Consultant Physician-Scientist, Intermediate Editor, Senior Postdoctoral Fellow, Senior Researcher, Department of Diabetes & Endocrinology, G.D Hospital & Diabetes Institute, 133A, Lenin Sarani, Kolkata 700013, West Bengal, India. draksingh_2001@yahoo.com
Received: March 7, 2022
Peer-review started: March 7, 2022
First decision: April 17, 2022
Revised: April 19, 2022
Accepted: May 21, 2022
Article in press: May 21, 2022
Published online: June 15, 2022
Abstract

SGLT-2 inhibitors (SGLT-2Is) have significantly improved cardio-renal outcomes and are preferred agents in people with cardiovascular diseases, heart failure, and diabetic kidney disease. Similarly, GLP-1 receptor agonists (GLP-1RAs) have significantly improved atherosclerotic cardiovascular outcomes. To this end, DPP-4 inhibitors (DPP-4Is) are cardiac-neutral drugs. While long-acting GLP-1RAs have shown a favorable HbA1c lowering compared to DPP-4Is, there is no clinically meaningful HbA1c lowering difference between SGLT-2Is vs DPP-4Is. Moreover, the glucose-lowering potential of SGLT-2Is gets compromised with a progressive decline in renal functions, unlike DPP-4Is. Furthermore, the HbA1c lowering potential of DPP-4Is is favorable in people with T2DM having a modest baseline HbA1c (8.0%-8.5%) compared with SGLT-2Is which lowers HbA1c larger in a background of higher baseline HbA1c (> 8.5%-9.0%). These findings suggest that the role of DPP-4Is in the management of type 2 diabetes mellitus cannot be completely ignored even in the era of SGLT-2Is.

Keywords: DPP-4 inhibitors, SGLT-2 inhibitors, GLP-1 receptor agonists, Cardiovascular outcomes, Renal outcomes

Core Tip: Despite the newer anti-diabetic agents such as SGLT-2 inhibitors (SGLT-2Is) and GLP-1 receptor agonists have taken the center stage in the management of type 2 diabetes mellitus due to additional cardiac and renal benefits, the role of DPP-4 inhibitors (DPP-4Is) cannot be undermined. HbA1c lowering potential of DPP-4Is are nearly similar to SGLT-2Is and surprisingly larger in a background of modest baseline HbA1c compared with SGLT-2Is. Moreover, the HbA1c lowering abilities of SGLT-2Is are compromised with declining renal function while DPP-4Is reduce HbA1c favorably in people with chronic kidney disease regardless of impaired kidney functions.