The association between glucagon-like peptide-1 receptor agonists and reported musculoskeletal adverse events: a systematic review and meta-analysis of randomized controlled trials

Background: Obesity is a major risk factor for musculoskeletal disorders. Glucagon-like peptide-1 receptor (GLP-1R)-based agonists facilitate weight loss and may influence musculoskeletal health. However, whether GLP-1R based agonists are associated with the musculoskeletal adverse events during the treatment remains unclear. Objectives: To assess the association between the use of GLP-1R agonists (GLP-1RA) and the spontaneous reports of musculoskeletal adverse events based on RCT safety data. Design: A systematic review and meta-analysis of RCTs. Methods: , the Cochrane Center Register of Controlled Trials for Studies, and Clinicaltrial.gov website were searched for RCTs of GLP-1R-based agonists from the inception to June 2025. The primary endpoint was the association between GLP-1R-based agonists and the reported musculoskeletal adverse events, expressed as risk ratio with the 95% confidence interval (CI) using a random-effect model. Results: A total of 43 RCTs with 100,488 participants were included. No significant difference was observed between users of GLP-1RAs and the control group in the reporting of the prespecified musculoskeletal adverse events, including gouty arthritis, rheumatoid arthritis, osteoarthritis, osteoporotic fracture, synovitis, or intervertebral disc protrusion. However, a higher proportion of male participants was associated with fewer reports of osteoarthritis (β = -0.015, 95% CI, -0.029 to -0.001) in GLP-1R-based agonist users. Conclusion: GLP-1RAs were not associated with the spontaneously reported events of gouty arthritis, rheumatoid arthritis, osteoarthritis, osteoporotic fracture, synovitis, or intervertebral disc protrusion. A higher percentage of male participants was associated with fewer reports of osteoarthritis among GLP-1RA users.