Practical management of glucagon-like peptide-1 receptor agonists in gastroenterology: a position paper by the Italian Society of Gastroenterology (SIGE)

: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes and obesity, conditions frequently encountered in gastroenterological practice. Their pleiotropic effects along the gut-pancreas-liver axis have raised both therapeutic interest and safety concerns, particularly regarding hepatic outcomes, gastrointestinal cancers, peri-endoscopic management, and gastrointestinal adverse events. This position paper, endorsed by the Italian Society of Gastroenterology (SIGE), was developed according to the GRADE framework and provides evidence-based recommendations for the safe and effective management of GLP-1RAs in gastroenterology, highlighting their favorable benefit-risk profile while identifying key knowledge gaps requiring future prospective studies. GLP-1RAs may be safely used in patients with diabetes or obesity and metabolic dysfunction-associated steatotic liver disease. In cirrhotic patients with diabetes or obesity, GLP-1RAs appear safe and are associated with reduced hepatic decompensation. Available evidence does not support an increased risk of esophageal, gastric, colorectal, or pancreatic cancer, while a potential reduction in hepatocellular carcinoma incidence is suggested. Routine discontinuation of GLP-1RAs before upper gastrointestinal endoscopy is not recommended. GLP-1RAs increase the risk of mild, transient gastrointestinal adverse events and cholelithiasis but are not associated with severe gastrointestinal complications or acute pancreatitis.