Effect of glucagon-like peptide-1 receptor agonists in osteoarthritis: A systematic review of pre-clinical and human studies.

Objective: There is significant interest in the potential of glucagon-like peptide 1 receptor agonists (GLP-1A) to improve outcomes in osteoarthritis. We systematically reviewed the evidence from pre-clinical and human studies for effect of glucagon-like peptide 1 receptor agonists (GLP-1A) in osteoarthritis. Method: Ovid Medline, Embase and CINAHL were searched (inception to November 2024) using MeSH terms and key words to identify studies examining the association between GLP-1A use and outcomes related to osteoarthritis. Risk of bias assessment and data extraction were conducted by three reviewers independently. Qualitative evidence synthesis was performed and prospectively registered on PROSPERO (CRD42024522782 and CRD42024522787). Results: This systematic review included 11 (7 pre-clinical; 4 human studies) studies. In pre-clinical studies, GLP-1A was assessed for its effect on structural (n ​= ​6); immunomodulation (n ​= ​7); analgesia (n ​= ​1) and molecular pathways in osteoarthritis (n ​= ​5). For human studies, GLP-1A were assessed for structural (n ​= ​1) and symptomatic (n ​= ​4) effects in osteoarthritis. Pre-clinical studies consistently demonstrated favourable chondroprotective and immunomodulatory effects of GLP-1A in osteoarthritis, with a dose-dependent effect, primarily driven by inhibition of NF-κB pathway. Limited human studies supported these findings in osteoarthritis. Conclusion: There are consistent signals across limited pre-clinical and human studies to support a potential favourable structural protective, immunomodulatory and analgesic effects of GLP-1A in osteoarthritis. With the growing burden of obesity, high-quality trials are needed to determine the role of GLP-1A in osteoarthritis.