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

Abstract

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.