To evaluate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) on gastrointestinal adverse reactions in patients with type 2 diabetes mellitus (T2DM).

The databases PubMed, Embase, and Cochrane Library were systematic searched for randomized controlled trials of GLP-1RA for the treatment of T2DM from the time of construction until October 1st, 2023, with one GLP-1RA as the drug in the trial arm and placebo or another GLP-1RA as the drug in the control arm. Bayesian network meta-analysis was used to explore the risk of gastrointestinal adverse reactions, such as nausea, vomiting, anorexia, constipation, dyspepsia, and diarrhea.

Forty-five papers were included, involving 27 729 patients. The overall incidence of gastrointestinal adverse reactions caused by GLP-RA was 11.66%. Compared with placebo, tirzepatide caused the highest risk of nausea, diarrhea, dyspepsia, and anorexia, lixisenatide caused the highest risk of vomiting, and semaglutide caused the highest risk of constipation. Compared with placebo, all GLP-1RA except loxenatide significantly increased the risk of vomiting; all GLP-1RA except lixisenatide significantly increased the risk of diarrhea; all GLP-1RA significantly increased the risk of constipation except tirzepatide and lixisenatide; all GLP-1RA significantly decreased appetite and increased the risk of dyspepsia (P<0.05).

GLP-1RA significantly increased the risk of gastrointestinal adverse reactions in T2DM patients, and different drugs have different risks of various symptoms, among which tirzepatide has a higher risk of gastrointestinal symptoms, which deserves clinical attention and vigilance.