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
Abstract
BACKGROUND

Since adverse events during treatment affect adherence and subsequent glycemic control, understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus (T2DM) therapy.

AIM

To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4 (DPP-4) inhibitors.

METHODS

Electronic databases were searched. The selection criteria included randomized controlled trials focused on cardiovascular outcomes. In these studies, the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo. Six trials involving 53616 patients were deemed eligible. We calculated aggregate relative risks employing both random-effects and fixed-effects approaches, contingent upon the context.

RESULTS

The application of DPP-4 inhibitors showed no significant link to the overall infection risk [0.98 (0.95, 1.02)] or the risk of serious infections [0.96 (0.85, 1.08)], additionally, no significant associations were found with opportunistic infections [0.69 (0.46, 1.04)], site-specific infections [respiratory infection 0.99 (0.96, 1.03), urinary tract infections 1.02 (0.95, 1.10), abdominal and gastrointestinal infections 1.02 (0.83, 1.25), skin structure and soft tissue infections 0.81 (0.60, 1.09), bone infections 0.96 (0.68, 1.36), and bloodstream infections 0.97 (0.80, 1.18)].

CONCLUSION

This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.

Keywords: Dipeptidyl peptidase-4 inhibitors; Type 2 diabetes mellitus; Overall infection; Site-specific infections; Meta-analysis

Core Tip: This meta-analysis revealed no significant correlation between dipeptidyl peptidase-4 (DPP-4) inhibitor usage and the risk of overall, serious, opportunistic, or site-specific infections in patients with type 2 diabetes participating in cardiovascular outcome trials. These findings suggest that DPP-4 inhibitors do not pose a heightened risk of infections compared to other treatments used for these patients. However, further long-term studies and real-world surveillance are warranted to examine the broader implications of DPP-4 inhibitors therapy on infection susceptibility in clinical settings.