Original Investigation

GLP-1 Receptor Agonists and Noncardiometabolic Outcomes

JAMA Network Open 10.1001/jamanetworkopen.2026.4722

March 31, 2026 at 11:00 AM EDT

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What are the associations between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and noncardiometabolic outcomes, and how credible is the available evidence?In this umbrella review of 60 meta-analyses of 1751 randomized clinical trials involving approximately 3 million participants, the most consistent associations with GLP-1 RAs were increased gastrointestinal adverse events (including nausea and vomiting). Suggested protective associations were reported for serious infections and respiratory disease, while possible associations with pancreatitis and gallbladder or biliary disease remained exploratory.This review observed signals of an association between GLP-1 RAs and lower risks of respiratory disease and serious infections; however, the credibility of the evidence was limited and require further confirmation.

Corresponding Authors: Yongze Li, PhD, Department of Endocrinology and Metabolism, The Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, No. 155, Nanjing Bei St, Shenyang 110001, PR China (yzli87@cmu.edu.cn); Qiqiang Guo, PhD, The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, China (qqguo@cmu.edu.cn).

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