The Impact of Glucagon-like Peptide-1 Receptor Agonists on Osteoarthritis in Non-Weight-Bearing Joints: A Narrative Review

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes mellitus (T2DM) and obesity, with well-documented benefits for weight reduction, glycemic control, and cardiovascular health. Preclinical evidence and emerging clinical data suggest that GLP-1 RAs may exert anti-inflammatory and chondroprotective effects relevant to osteoarthritis (OA). While most research focuses on weight-bearing joints, the potential impact on non-weight-bearing joints remains unclear. The available evidence utilized in this review was in the form of clinical studies, database analyses, and animal models. The databases of PubMed, Embase, Cochrane Library, and Google Scholar were utilized to extract data. Search criteria included “GLP-1 receptor agonist”, “Ozempic”, “osteoarthritis”, “inflammation”, “non-weight-bearing joints”, “shoulder osteoarthritis”, and “hand osteoarthritis”. When non-weight-bearing joint-specific literature was unavailable, evidence from weight-bearing joints was examined to infer possible implications. Preclinical studies demonstrate that GLP-1 RAs can reduce pro-inflammatory cytokines, inhibit chondrocyte apoptosis, and modulate NF-κB signaling in joint tissues. In human OA cohorts, GLP-1 RA use has been associated with slower cartilage loss, lower pain scores, and reduced rates of arthroplasty in patients with established OA, including effects not fully explained by weight loss. However, large database studies have also reported increased OA diagnoses in individuals using GLP-1 RAs with no pre-existing disease. Although direct evidence in non-weight-bearing OA is sparse, findings from weight-bearing joint studies suggest a potential disease-modifying role for GLP-1 RAs, alongside possible risks. The heterogeneity of reported effects underscores the need for targeted clinical trials in hand, wrist, and shoulder OA.