Sydney Pomenti, Annabel Gerber, David A. Katzka, Michael Camilleri, Chin Hur
BACKGROUND: Obesity affects over 40% of the US population and contributes to worse outcomes in a variety of diseases and disorders. Glucagon-like peptide-1 receptor agonists have drawn attention for their impact on obesity. With a dense population of receptors throughout the gastrointestinal tract, it is critical to understand the way that glucagon-like peptide-1 receptor agonists impact gastrointestinal diseases and disorders. AIMS: To evaluate the expanding role of glucagon-like peptide-1 receptor agonists in the management of obesity and gastrointestinal disease, with a focus on therapeutic applications, impact on gastrointestinal cancers, safety profile, and implications for gastroenterology practice. METHODS: We conducted a narrative review of recent clinical trials, cohort studies, and guideline updates through 2025. Evidence was synthesised on efficacy, safety, and clinical implications across gastrointestinal disorders including steatotic liver disease, gastroesophageal reflux, inflammatory bowel disease, short bowel syndrome, and obesity-associated cancers. RESULTS: Glucagon-like peptide-1 receptor agonists induce substantial and durable weight loss and improve obesity-related gastrointestinal outcomes. They are approved for steatotic liver disease, with demonstrated histologic and biochemical benefits. Evidence suggests a reduced incidence of several gastrointestinal cancers. The most common adverse events include nausea, vomiting, diarrhoea, constipation, and delayed gastric emptying, which may affect peri-endoscopic management. Discontinuation rates remain substantial but can be mitigated by careful titration and specialist oversight. CONCLUSIONS: Glucagon-like peptide-1 receptor agonists are a critical therapy for obesity and several related gastrointestinal conditions. Gastroenterologists are uniquely positioned to optimize their use, manage adverse events, coordinate multidisciplinary care, and ensure safe and effective integration into practice.