Core Viewpoint - Semaglutide, developed by Novo Nordisk, is a GLP-1 receptor agonist approved for treating type 2 diabetes and obesity, showing significant weight loss and potential benefits for cardiovascular health and cancer risk reduction [3][4]. Group 1: Clinical Research Findings - A study published in NEJM in October 2024 demonstrated that semaglutide significantly reduces weight and alleviates pain from obesity-related knee osteoarthritis, enhancing exercise participation [3]. - A subsequent study in Cell Metabolism revealed that semaglutide exhibits notable cartilage protection in metabolic osteoarthritis, independent of weight loss, challenging traditional beliefs about osteoarthritis treatment [4][5]. - The research indicated that semaglutide improves cartilage cell metabolism from glycolysis to oxidative phosphorylation, providing a new mechanism for osteoarthritis treatment [7][9]. Group 2: Mechanism of Action - Semaglutide activates the GLP-1R-AMPK-PFKFB3 signaling axis, facilitating cartilage repair under inflammatory conditions [7][9]. - The study confirmed that semaglutide's therapeutic effects on osteoarthritis are not solely due to weight loss, highlighting its unique metabolic restoration capabilities [6][9]. Group 3: Clinical Implications - In a randomized pilot clinical trial, semaglutide significantly improved knee function scores in obese patients with knee osteoarthritis compared to current treatments like sodium hyaluronate injections [6]. - The findings suggest that semaglutide could become an effective drug for treating metabolic osteoarthritis, opening new avenues for drug development [5][9].