Efficacy and Safety of GLP-1 Receptor Agonists for the Management of Knee Osteoarthritis: A Systematic Review and Meta-Analysis

Background and Objective: Osteoarthritis (OA) represents a leading cause of chronic pain and disability globally. While current management primarily addresses symptom relief, disease-modifying interventions remain limited. Obesity significantly contributes to osteoarthritis progression especially knee osteoarthritis (KOA), with weight reduction yielding symptomatic benefits. GLP-1RAs, originally developed for type 2 diabetes and obesity management, show potential in KOA management through weight-reducing and anti-inflammatory mechanisms. Method and Results: This systematic review and meta-analysis evaluated GLP-1RAs' efficacy and safety in KOA, focusing on pain reduction, functional improvement, and weight loss outcomes. Our comprehensive database search identified two randomized controlled trials with 563 participants that met inclusion criteria, both examining semaglutide and liraglutide against placebo. Results demonstrated that GLP-1RA-treated patients experienced significantly greater reductions in body weight (-7.8 kg; 95% CI: -9.2 to -6.4) and Body-mass Index (BMI) (-2.8 kg/m²; 95% CI: -3.3 to -2.3). Gastrointestinal effects constituted the primary adverse events. Both studies demonstrated low risk of bias with no detected publication bias. Conclusion: These findings suggest GLP-1RAs may represent promising therapeutic agents for KOA by addressing both weight-related and inflammatory pathways underlying disease progression. Larger trials investigating long-term efficacy and safety are warranted.