Osteoarthritis (OA) is the most common form of arthritis, affecting over 500 million people globally. Current treatments are primarily symptom-focused, with no approved therapies to halt disease progression. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used in type 2 diabetes (T2D) and obesity, demonstrate significant weight loss and glucose-lowering effects and have been shown to possess anti-inflammatory properties. Given the central role of inflammation and metabolic dysfunction in OA, this review examines the potential utility of GLP-1 RAs in OA management, focusing on both indirect effects, such as weight reduction, and possible direct effects on inflammatory pathways and cartilage preservation. Clinical studies suggest that GLP-1 RAs may benefit people with OA by reducing weight, improving glycemic control, and modulating inflammatory markers relevant to OA progression. Notable findings include significant weight loss and pain reduction in people with knee OA (KOA) treated with semaglutide in the STEP-9 trial. In other studies, GLP-1 RAs have shown potential to lower oxidative stress and pro-inflammatory cytokines, such as tumor necrosis factor (TNF-α) and interleukin (IL)-6, with reductions in OA-related pain and functional impairment observed in some cohorts. However, results vary, with some studies showing limited effects, potentially linked to the degree of weight loss achieved. Although some studies report variability in pain relief, likely influenced by the degree of weight loss achieved, GLP-1 RAs have shown overall promise in reducing both OA symptoms and markers associated with disease progression. This emerging evidence supports the utility of GLP-1 RAs as a potential disease-modifying option for OA, offering a dual benefit in metabolic and joint health. Future research should focus on establishing the long-term efficacy and safety and elucidating the mechanism by which GLP-1 RAs influence OA pathology.
