If the evidence is there, why are GLP-1 receptor agonists not on-label for hip and knee osteoarthritis in overweight patients?

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have rapidly emerged as highly effective pharmacological tools for weight management, with additional cardiometabolic benefits extending beyond obesity and diabetes. Despite compelling evidence, their potential role in osteoarthritis (OA) remains unrecognized in current regulatory frameworks. Hip and knee OA, leading causes of disability and healthcare burden worldwide, are strongly influenced by both biomechanical overload and systemic metabolic-inflammatory pathways. Increasing data support the dual capacity of GLP-1 RAs to achieve clinically meaningful weight reduction and to exert direct anti-inflammatory and chondroprotective effects within the joint. The STEP 9 trial and complementary real-world evidence demonstrate substantial improvements in OA symptoms, paralleled by reductions in surgical risk, while ongoing trials such as STOP-KNEE OA will further clarify their structural impact. Importantly, patients with a body mass index (BMI) of 27-29.9 kg/m²-currently excluded from GLP-1 RA eligibility unless additional comorbidities are present-may particularly benefit, as weight loss beyond 7-10% appears necessary to meaningfully alter OA trajectories. Recognizing symptomatic hip and knee OA as weight-related comorbidities would align regulatory labels with emerging science, expand therapeutic access, and foster integrated management of musculoskeletal and metabolic diseases. This Viewpoint argues that failure to acknowledge OA as an on-label indication for GLP-1 RAs represents a missed opportunity for patients, clinicians, and health systems.