The Role of GLP-1 Receptor Agonists In Rheumatic Diseases and Osteoarthritis: A Literature Review

Osteoarthritis (OA) and rheumatic diseases such as rheumatoid arthritis (RA) and psoriatic arthritis are increasingly recognized as chronic inflammatory disorders, rather than solely mechanical or autoimmune conditions. Inflammation plays a central role in the pathogenesis of these diseases, driving cartilage degradation, joint pain, and structural damage via cytokines, matrix-degrading enzymes, and oxidative stress. Glucagon-like peptide-1 receptor agonists (GLP 1RAs), initially developed for type 2 diabetes and obesity, have emerged as potential diseasemodifying agents in joint diseases due to their anti-inflammatory and immunomodulatory properties. Preclinical studies show that GLP 1RAs—such as liraglutide, semaglutide, and dulaglutide—reduce chondrocyte apoptosis, suppress NF κB and NLRP3 inflammasome activation, inhibit matrix metalloproteinases, and modulate macrophage polarization. These effects translate into protection against cartilage degeneration and synovial inflammation. Early human trials, including the STEP 9 study, demonstrate substantial reductions in OA-related knee pain and systemic inflammation, surpassing outcomes expected from weight loss alone. Limited evidence also supports their potential benefit in RA and psoriatic arthritis. Despite promising results, large-scale randomized controlled trials are lacking, and further research is needed to clarify long-term safety, efficacy, and direct comparisons with standard rheumatologic therapies. GLP 1RAs offer a novel and promising therapeutic avenue for inflammationdriven joint diseases, potentially redefining treatment strategies for OA and rheumatic conditions.