In May 2022, the research results of Zhang Huabing’s team from the Department of Endocrinology, PUMCH were published in the internationally renowned medical journal “JAMA Internal Medicine” (IF=44.409). After retrieving relevant randomized controlled trials on MEDLINE/PubMed, EMBASE, Web of Science, Cochrane Library, and clinical trial registry websites, the research team included a total of 76 randomized clinical trials for meta-analysis, and assessed the association of the novel hypoglycemic agent glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with the occurrence of gallbladder or biliary diseases. The study showed that GLP-1 RAs were associated with gallbladder or biliary diseases.
GLP-1 RAs can lower blood glucose and improve metabolism. Large-scale randomized controlled studies have confirmed that some GLP-1 RAs can reduce the occurrence of heart attacks, stroke events and even death. Current national and international guidelines for diabetes management recommend the preferential use of GLP-1 RAs in patients with type 2 diabetes who are at high risk for cardiovascular disease or have been diagnosed with cardiovascular diseases. Some GLP-1 RAs have been approved for weight loss treatment abroad and have become very promising drugs for weight loss. Thus a comprehensive evaluation of GLP-1 RAs is of great practical importance.
From 7,214 initial studies, the study selected 76 randomized controlled studies comparing the use of GLP-1 RA drug and placebo, or non-GLP-1 RA drug, enrolling a total of 103,371 patients, to systematically evaluate the association of GLP-1 RAs with the occurrence of gallbladder or biliary diseases. This study also evaluated whether the GLP-1 RA dosage, duration of administration, and purpose of treatment had an impact on the occurrence of gallbladder or biliary tract diseases.
This study found that use of GLP-1 RAs was associated with gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss. However, it is worth noting that weight loss itself increases the risk of biliary diseases, and it is unclear whether the increase in gallbladder and biliary events is due to weight loss associated with the use of GLP-1 RAs or other mechanisms.
For patients confirmed to have cardiovascular diseases, it was estimated that every 1,000 people treated with GLP-1 RAs would see an absolute reduction of 37 cardiovascular events over 5 years, and the use of GLP-1 RAs in these 1,000 people over 5 years was associated with only 6.5 additional gallbladder or biliary events. Thus the absolute risk of GLP-1 RAs increasing gallbladder or biliary diseases is not high, and we need to base our treatment decisions on this absolute risk for rational use of GLP-1 RAs.
As one of the most important subjournals of “JAMA”, “JAMA Internal Medicine” has a wide academic influence, and this study was featured in the current issue of “JAMA Internal Medicine” with a review by Professor Shanzay Haider, a renowned expert from Yale University, who highly recognized the value of this study in informing clinical drug use. The findings of this study were also covered by “BMJ News”, “ACP Diabetes Monthly” and many other famous academic media outlets.
Gallbladder or biliary diseases occurrence comparison between patients treated with GLP-1 RAs and those in the control group
Written by: The Department of Endocrinology
Picture courtesy: The Department of Endocrinology
Translator: Liu Haiyan
Editor: Yang Hongbo and Wang Yao