Impact of GLP-1 receptor agonists on gastrointestinal function and symptoms.

Abstract

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for diabetes, obesity, and metabolic liver disease, but are also used off-label for other conditions. Adverse events associated with GLP-1RAs have become evident with their increased use.

Areas covered: This review characterizes GLP-1 physiology and GLP-1RA effects on gastrointestinal (GI) function and symptoms. A comprehensive literature search was conducted accessing PubMed and EMBASE databases from July 1987 through August 2025. Effects of GLP-1RAs on parameters of dysfunctional GI transit and motility and symptoms potentially associated with these impairments are highlighted. The additional impact of GLP-1RA induced gastric food retention on the risk for pulmonary aspiration during anesthesia is a focus of concern. Extraintestinal complications including biliary tract disease and pancreatitis are discussed. Management of GLP-1RA adverse events is reviewed including adjustment of dosing protocols, dietary modifications, and pharmacotherapy to target GI symptoms, however these recommendations lack evidence-based support. New GLP-1RAs are in testing, many with action on other incretin pathways, but these may have adverse consequences similar to existing agents.

Expert opinion: Prospective investigations of multicenter databases are advocated to transform management approaches of these GLP-1RA induced GI functional consequences and adverse symptoms from empiric treatments to more evidence-based protocols.