“Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended for patients with type 2 diabetes to control glycemia and reduce cardiovascular risk, and for patients with obesity to reduce weight. Given the wide-spread use of these drugs, potential safety concerns deserve attention.
Several randomized clinical trials (RCTs) have shown a higher rate of gallbladder disorders in patients who were randomized to GLP-1 RAs vs a placebo. However, whether
increased risk of gallbladder-related events is a class effect of GLP-1 RAs has not been established, and prescribing information for all GLP-1 RA medications does not provide a warning regarding increased risk of gallbladder disorders. In addition to gallbladder-related events, a post hoc analysis of the LEADER trial 8 found significantly increased risks of acute biliary obstruction in patients randomized to liraglutide compared with placebo. Because
GLP-1 RAs are generally prescribed at higher doses for weight loss rather than for control of type 2 diabetes, there may be differential effects on risk for gallbladder or biliary diseases depending on dose.”

“This systematic review and meta-analysis of 76 randomized clinical trials found that randomization to treatment with GLP-1 RAs compared with placebo or active controls was associated with increased risk of the composite outcome of gallbladder or biliary diseases and for cholelithiasis, cholecystitis, and biliary diseases. Risk was increased in trials of patients treated for diabetes and for weight loss and was higher in the trials for
weight reduction. Higher doses and longer duration of GLP-1 RAs treatment were also associated with increased risk of gallbladder or biliary diseases, although the association was not statistically significant.
Previous systematic reviews have reported an increased risk of cholelithiasis with GLP-1 RA use, but these reviews were limited to trials with restrictions on populations and duration of treatment and did not include several important studies that have been published recently.”

He, Liyun et al. “Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials.” JAMA internal medicine vol. 182,5 (2022): 513-519. doi:10.1001/jamainternmed.2022.0338 Free Full Text