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

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.

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.

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.