Excessive body weight stands out as a major, well-documented risk factor for rheumatic and musculoskeletal diseases (RMDs). Indeed, high body mass index (BMI) affects disease severity, treatment response, and long-term outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were first developed for type 2 diabetes and obesity, but there is growing evidence that they may also have anti-inflammatory and immunomodulatory properties [1-3]. This narrative review examines the available evidence on the role of GLP-1 RAs in two conditions that are strongly associated with metabolic and mechanical factors but sit on almost opposite ends of the inflammatory spectrum: osteoarthritis (OA), a predominantly mechanically driven disease, and psoriatic disease (PsD), an immune-mediated inflammatory disease. A comprehensive narrative review of the literature was conducted to evaluate preclinical and clinical evidence regarding the effects of GLP-1 signaling in both OA and PsD. Preclinical data suggest that GLP-1 signaling may protect cartilage, reduce inflammation, and alleviate pain in OA. Early clinical evidence is encouraging, showing reductions in both joint pain and body weight. In PsD, obesity and psoriatic inflammation share several common pathways, particularly through the IL-17/IL-23 axis, which provides a theoretical biological rationale for GLP-1 RAs use in this setting, although direct clinical evidence remains limited and largely derived from studies in obese patients. Dedicated randomized controlled trials are necessary to clarify the direct immunomodulatory mechanisms involved and to define the precise position of GLP-1 RAs in rheumatological practice.
