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Cited by 46Diabetes Treatment and ManagementPharmacology and Obesity TreatmentPharmacovigilance and Adverse Drug Reactions

GLP-1RAs caused gastrointestinal adverse reactions of drug withdrawal: a system review and network meta-analysis

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Zhang, Ziqi, Zhang, Qiling, Tan, Ying, Chen, Yu, Zhou, Xiqiao, Liu, Su, Yu, Jiangyi·2023·Frontiers in Endocrinology
DOI 10.3389/fendo.2023.1149328PMC PMC10359616
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Abstract

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly reduce postprandial blood glucose, inhibit appetite, and delay gastrointestinal emptying. However, it is controversial that some patients are intolerant to GLP-1RAs. Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials (RCTs) using GLP-1RAs with documented withdrawal due to gastrointestinal adverse reactions (GI AEs) from their inception to September 28, 2022. After extracting the information incorporated into the studies, a random-effects network meta-analysis was performed within a frequentist framework. Results: 64 RCTs were finally enrolled, which included six major categories of the GLP-1RA. The sample size of the GLP-1RAs treatment group was 16,783 cases. The risk of intolerable gastrointestinal adverse reactions of Liraglutide and Semaglutide was higher than that of Dulaglutide. Meanwhile, the higher the dose of the same GLP-1RA preparation, the more likely to cause these adverse reactions. These intolerable GI AEs were not significantly related to drug homology or formulations and may be related to the degree of suppression of the appetite center. Conclusion: Dulaglutide caused the lowest intolerable GI AEs, while Liraglutide and Semaglutide were the highest. For Semaglutide, the higher the dose, the more likely it is to drive GI AEs. Meanwhile, the risk of these GI AEs is independent of the different formulations of the drug. All these findings can effectively guide individualized treatment. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359346 , identifier CRD42022359346.

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  • The findings are consistent with prior research in diabetic populations.

    “Nausea was the most frequently reported symptom, besides vomiting and diarrhea, findings consistent with prior research in diabetic populations [51–56].”

    From Gastrointestinal adverse events associated with GLP-1 RA in non-diabetic patients with overweight or obesity: a systematic review and network meta-analysis (2025) · cites this paper as [52]

    The Introduction names nausea, vomiting, and diarrhea as gastrointestinal adverse reactions that can lead to drug discontinuation, and the Results table includes studies in diabetic populations. But the paper does not establish that nausea was reported more frequently than vomiting or diarrhea; its analysis focuses on gastrointestinal reactions leading to withdrawal rather than the frequency of each symptom. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Zhang, Z., Zhang, Q., Tan, Y., Chen, Y., Zhou, X., Liu, S., & Yu, J.
Affiliations
Nanjing University of Chinese Medicine (CN)
Corresponding author
Yu, Jiangyi
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2023-07-06
Volume
14
Pages
1149328-1149328
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2023.1149328
PMC
PMC10359616
OpenAlex
W4383313330
Cited by
46
References
22
Citations by year
2026: 14 · 2025: 18 · 2024: 13 · 2023: 1
FWCI
1.66
Type
journal article
Language
en
Update notices
corrigendum (2023-10-09)
Open access
Licence
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (8774117)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Keywords
GLP-1 receptor agonists, gastrointestinal adverse effects, drug intolerance, drug withdrawal, liraglutide, semaglutide, dulaglutide, dose-response relationship, appetite suppression, type 2 diabetes treatment
MeSH terms
Glucagon-Like Peptide-1 Receptor, Liraglutide, Network Meta-Analysis, Glucagon-Like Peptide-1 Receptor Agonists, Blood Glucose, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents

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