INCIDENCE, SEVERITY, AND DISCONTINUATION DUE TO GASTROINTESTINAL ADVERSE EVENTS ASSOCIATED WITH GLP-1 RECEPTOR AGONISTS IN THE TREATMENT OF TYPE 2 DIABETES MELLITUS: A SYSTEMATIC REVIEW

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are among the main therapeutic options for the treatment of type 2 diabetes mellitus (T2DM), improving glycemic control, promoting weight loss, and reducing cardiovascular risk. However, these agents are frequently associated with gastrointestinal adverse events that may affect treatment adherence. This systematic review aimed to evaluate the incidence, severity, and treatment discontinuation related to gastrointestinal adverse events associated with GLP-1RAs in patients with T2DM. The review was conducted according to the PRISMA 2020 guidelines and included randomized controlled trials identified through scientific databases. Nine studies met the eligibility criteria, comprising approximately 5,402 participants. Nausea was the most common adverse event, with an estimated overall incidence of 15–17%, followed by diarrhea (12–14%) and vomiting (<8%). Tirzepatide showed the highest frequency of gastrointestinal symptoms, whereas dulaglutide demonstrated the most favorable tolerability profile. Despite the high incidence of adverse events during the first weeks of treatment, discontinuation rates remained low, generally below 8%, indicating that most symptoms are transient and manageable. Overall, GLP-1RAs present a favorable benefit-risk profile, particularly when gradual dose escalation and appropriate patient counseling are implemented.