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

Front Endocrinol (Lausanne). 2023 Jul 6:14:1149328. doi: 10.3389/fendo.2023.1149328. eCollection 2023.

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.

Keywords: Dulaglutide; Glucagon-like peptide-1 receptor agonist; Liraglutide; Semaglutide; gastrointestinal adverse effects; intolerance; network meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Blood Glucose
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucagon-Like Peptide-1 Receptor* / agonists
  • Humans
  • Hypoglycemic Agents* / therapeutic use
  • Liraglutide / therapeutic use
  • Network Meta-Analysis

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Liraglutide
  • Glucagon-Like Peptide-1 Receptor

Grants and funding

The study was funded by the National Natural Science Foundation of China (Grant number: 81774117). The funding source was used for article processing charges. Beyond that, the study’s funder had no role in study design, data collection, analysis, interpretation, or report writing.