GLP-1 Receptor Agonists up Risk of Gallbladder and Biliary Disease

GLP-1 RAs are generally prescribed at higher doses for weight loss rather than for control of type 2 diabetes. However, the associations of GLP-1 RAs with gallbladder or biliary diseases are controversial. Therefore, Dr Liyun He, MM and her team conducted a study to evaluate the association of GLP-1 RA treatment with gallbladder and biliary diseases and to further explore the risk factors for these associations.

In a systematic review and meta-analysis, the researchers searched MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane Library for randomized clinical trials (RCTs) comparing the use of GLP-1 RA drugs with placebo or with non−GLP-1 RA drugs in adults. They calculated pooled relative risks (RRs) using random or fixed-effects models and further assessed the quality of evidence for each outcome using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. The major outcome assessed was the composite of the gallbladder or biliary diseases. They also assessed biliary diseases, biliary cancer, cholecystectomy, cholecystitis, and cholelithiasis.

Key findings of the study:

• The researchers included a total of 76 RCTs involving 103 371 patients.
• Upon analysis, the researchers found that the GLP-1 RA treatment was associated with increased risks of the gallbladder or biliary diseases (RR, 1.37); specifically, cholelithiasis (RR, 1.27), cholecystitis (RR, 1.36), and biliary disease (RR, 1.55).
• They also found that the use of GLP-1 RAs was associated with an increased risk of gallbladder or biliary diseases in trials for weight loss (n = 13; RR, 2.29) and type 2 diabetes or other diseases (n = 63; RR, 1.27).
• They further noted that GLP-1 RA use was associated with higher risks of gallbladder or biliary diseases at higher doses (RR, 1.56) compared with lower doses (RR, 0.99) and with longer duration of use (RR, 1.40) compared with shorter duration (RR, 0.79).

The authors concluded, "The findings of this systematic review and meta-analysis indicate that physicians should be concerned about the increased risk of the gallbladder or biliary disease associated with GLP-1 RA use, especially at the higher doses recommended for weight loss. In addition, future trials should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes".

For further information:

DOI:10.1001/jamainternmed.2022.0338

Keywords:

GLP-1 RA, Glucagon-like peptide-1 receptor agonists, biliary disease, Gallbladder disease, higher doses, Longer duration of GLP-1 RA, cholelithiasis, cholecystitis, GRADE framework, biliary cancer, JAMA Internal Medicine.