Meta-Analysis
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2024; 15(5): 1011-1020
Published online May 15, 2024. doi: 10.4239/wjd.v15.i5.1011
Dipeptidyl peptidase-4 inhibitors and the risk of infection: A systematic review and meta-analysis of cardiovascular outcome trials
Na Yang, Li-Yun He, Peng Liu, Zi-Yi Li, Yu-Cheng Yang, Fan Ping, Ling-Ling Xu, Wei Li, Hua-Bing Zhang, Yu-Xiu Li
Na Yang, Li-Yun He, Zi-Yi Li, Yu-Cheng Yang, Fan Ping, Ling-Ling Xu, Wei Li, Hua-Bing Zhang, Yu-Xiu Li, Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Peng Liu, Department of Endocrinology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471000, Henan Province, China
Author contributions: Zhang HB, Li YX participated in the conceptualization, data curation, investigation, methodology, project administration, resources, and supervision; Yang N was involved in the formal analysis and writing of the original draft; He LY, Liu P, Li ZY, Yang YC were involved in the formal analysis; Ping F, Xu LL, Li W were involved in writing-review and editing.
Supported by CAMS Innovation Fund for Medical Sciences, No. 2023-I2M-C&T-B-043 and No. 2021-I2M-1-002; National High Level Hospital Clinical Research Funding, No. 2022-PUMCH-B-015; Beijing Municipal Natural Science Foundation, No. M22014; and National Natural Science Foundation of China, No. 91846106.
Conflict-of-interest statement: The authors declare no conflicts of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Hua-Bing Zhang, MD, Chief Doctor, Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing 100730, China. huabingzhangchn@163.com
Received: February 9, 2024
Peer-review started: February 11, 2024
First decision: February 19, 2024
Revised: March 6, 2024
Accepted: March 19, 2024
Article in press: March 19, 2024
Published online: May 15, 2024
Processing time: 91 Days and 9.6 Hours
ARTICLE HIGHLIGHTS
Research background

Inhibitors of dipeptidyl peptidase-4, also known as dipeptidyl-peptidase 4 (DPP-4) inhibitors, represent a widely adopted category of oral hypoglycemic medications favored for managing type 2 diabetes mellitus (T2DM), attributable to their efficacy in reducing blood sugar levels and favorable patient tolerability. However, given the role of DPP-4 in immune function, understanding the association between DPP-4 inhibitor use and infection risk is crucial for treatment adherence and long-term glycemic control.

Research motivation

Previous studies have reported conflicting results regarding the infection risk linked to the application of DPP-4 inhibitors in individuals with T2DM. With diabetes patients already at an increased risk for various infections, clarifying the safety profile of DPP-4 inhibitors in terms of infection risk is essential for informed clinical decision-making.

Research objectives

This meta-analysis aims to assess the risk of overall, serious, opportunistic, and site-specific infections in T2DM patients treated with DPP-4 inhibitors, using data extracted from cardiovascular outcome trials (CVOTs).

Research methods

A literature search across multiple databases was conducted to identify randomized controlled CVOTs contrasting DPP-4 inhibitors against placebos or operative antidiabetic substances in adult T2DM patients. Cumulative relative risks were calculated employing both random-effects and fixed-effects frameworks, considering the diversity of the trials included.

Research results

Six trials involving 53616 patients were included. The assessment uncovered that DPP-4 inhibitors' usage did not markedly escalate the risk of overall, serious, opportunistic, or site-specific infections. This was consistent across various infection types, including respiratory, urinary tract, abdominal, gastrointestinal, skin, soft tissue, bone, and bloodstream infections.

Research conclusions

The results suggest that DPP-4 inhibitors do not correlate with a heightened infection risk relative to control groups. This supports the continued use of DPP-4 inhibitors in T2DM therapy without added concerns for heightened infection risk.

Research perspectives

While the current meta-analysis provides reassurance about the infection risk associated with DPP-4 inhibitors, further long-term studies and real-world data are essential to thoroughly grasp the consequences of DPP-4 inhibition concerning infection susceptibility. This will help refine treatment strategies for T2DM patients, particularly those at high risk for cardiovascular events.