GLP-1 Receptor Agonists and Gastrointestinal Adverse Events

GLP-1 receptor agonists (GLP-1RAs) are medications commonly used to treat type 2 diabetes, obesity, and metabolic liver diseases. A meta-analysis of 55 randomized trials involving over 106,000 participants examined their gastrointestinal safety. The study found that GLP-1RAs are linked to a 46% higher risk of cholelithiasis (gallstones), which equals about 2 extra cases per 1000 people treated. Additionally, they were associated with a twofold increased risk of gastroesophageal reflux disease (GERD), leading to 4 extra cases per 1000 patients. However, no significant increase was observed in other gastrointestinal risks like pancreatitis, cholangitis, or intestinal obstruction.

The risks of gallstones and GERD were more pronounced in patients with obesity, liver conditions like MASLD/MASH, those using GLP-1RAs for weight loss, or taking higher doses. These effects may result from rapid weight loss and reduced gallbladder motility (for gallstones) or delayed gastric emptying (for GERD). Despite these risks, GLP-1RAs are considered safe overall, as severe gastrointestinal complications were not significantly elevated.

Clinicians should monitor gallbladder and reflux symptoms in patients on GLP-1RAs, especially those on weight-loss formulations or higher doses. The benefits of these drugs often outweigh their modest risks, making them a valuable therapeutic option.