SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1613610
This article is part of the Research TopicOptimizing GLP-1 Receptor Agonist Use: Mechanisms, Clinical Applications, and Safety ProfilesView all 10 articles
Comparative Gastrointestinal Adverse Effects of GLP-1 Receptor Agonists and Multi-Target Analogs in Type 2 Diabetes: A Bayesian Network Meta-Analysis in Type 2 Diabetes: A Bayesian Network Meta-Analysis
Provisionally accepted
- 1Department of Pharmacy, Guangzhou Eighth People's Hospital of Panyu District, Guangzhou, China
- 2Department of Pharmacy,Guangdong Second Provincial People's Hospital, Guangzhou, China
- 3Department of Internal Medicine, Guangzhou Eighth People's Hospital of Panyu District, Guangzhou, China
- 4College of Medicine, Shantou University, Shantou, Guangdong Province, China
- 5Third Affiliated Hospital, Southern Medical University, Guangzhou, China
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Objective: This study aims to evaluate and compare the gastrointestinal adverse effects associated with different GLP-1 receptor agonists (GLP-1RAs) and multi-target analogs in patients with type 2 diabetes mellitus (T2DM) using a Bayesian network meta-analysis.A systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov was conducted to identify randomized controlled trials (RCTs) assessing the gastrointestinal adverse events of GLP-1RAs in T2DM patients. Inclusion criteria included adult patients with confirmed T2DM receiving any GLP-1RA, with the outcomes focused on gastrointestinal adverse events such as nausea, vomiting, diarrhea, constipation, dyspepsia, and reduced appetite. Bayesian network meta-analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the comparison of gastrointestinal side effects among different GLP-1RAs.Results: A total of 48 RCTs involving 27,729 participants were included in the analysis. The overall incidence of gastrointestinal adverse events was 11.66%, with nausea being the most frequent (21.49%) and reduced appetite the least frequent (5.49%). Tirzepatide had the highest risk of inducing nausea and diarrhea, while dulaglutide and lixisenatide had the lowest risks. Exenatide exhibited the highest incidence of vomiting, while dulaglutide showed a lower risk. Semaglutide demonstrated a significantly higher risk of diarrhea compared to other GLP-1RAs.This study highlights significant differences in the gastrointestinal adverse event profiles of various GLP-1RAs. Tirzepatide exhibited the highest risk of gastrointestinal side effects, whereas dulaglutide and exenatide showed relatively better tolerability. These findings provide valuable insights for clinicians to make informed treatment decisions, emphasizing the importance of individualized therapy based on patient tolerance.
Keywords: GLP-1 receptor agonists, type 2 diabetes mellitus, gastrointestinal adverse events, Bayesian network meta-analysis, Nausea, Vomiting, Diarrhea
Received: 17 Apr 2025; Accepted: 21 Aug 2025.
Copyright: © 2025 Xie, Yang, Deng, Liu, Xu and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhibin Xu, College of Medicine, Shantou University, Shantou, 515041, Guangdong Province, China
Binghong He, Third Affiliated Hospital, Southern Medical University, Guangzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.