GLP-1RAs show promise for obesity-related knee osteoarthritis via weight loss, but direct structural benefits remain unproven.

Knee osteoarthritis (KOA), particularly obesity-related forms, is a major cause of pain and disability. Current management often treats adiposity as a background risk rather than a direct therapeutic target, leading to suboptimal outcomes. Excess weight exacerbates KOA through increased joint loading, low-grade inflammation, and metabolic dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), known for significant weight loss, present a novel approach to address this gap by targeting obesity directly.

This narrative review synthesized existing literature on GLP-1 receptor agonists in obesity-related knee osteoarthritis. Researchers examined the rationale, GLP-1R biology, pharmacological mechanisms, and inflammatory signaling hypotheses. They also evaluated clinical evidence, safety concerns, and implementation challenges. The review positioned GLP-1RAs within a broader obesity-treatment continuum, including lifestyle interventions, exercise, other anti-obesity medications, and bariatric surgery.

The review concluded that human data primarily supports GLP-1RA-mediated improvements in KOA pain, function, and rehabilitation feasibility, largely driven by weight loss. Direct cartilage, synovium, subchondral bone, or structure-modifying effects of GLP-1RAs in KOA remain unproven. > The evidence suggests GLP-1RAs are a useful component of integrated obesity-directed KOA care, but should be considered part of a proposed framework rather than validated disease-modifying therapy. Particular attention was given to common safety concerns like gastrointestinal intolerance, dehydration, gallbladder issues, and pancreatitis. The review also highlighted practical challenges such as lean-mass loss, perioperative management, treatment discontinuation, affordability, access, and long-term adherence.