Intra-articular injection of liraglutide attenuates capsular fibrosis and improves shoulder range of motion in a rat model of adhesive capsulitis

Abstract Adhesive capsulitis is a disabling shoulder disorder characterized by progressive pain and capsular fibrosis, for which intra-articular corticosteroid injection provides only short-term anti-inflammatory relief without directly targeting fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown anti-inflammatory and anti-fibrotic effects in other organ systems, but their potential in musculoskeletal fibrosis is unexplored. We evaluated intra-articular liraglutide in a rat model of adhesive capsulitis. Thirty rats were allocated at the outset into a non-immobilized sham group and four immobilized groups (saline, triamcinolone, low-dose liraglutide, high-dose liraglutide); two rats died during immobilization, leaving 28 for analysis. After 6 weeks of shoulder immobilization, each immobilized rat received a single intra-articular injection of its assigned agent. Passive shoulder abduction angle, capsular thickness, and immunohistochemical markers of fibrosis were assessed. A linear mixed-effects model showed a significant group-by-time interaction for abduction angle ( p = 0.002); at 3 weeks, all three treatment groups improved significantly more than saline. Capsular thickness and fibronectin expression were significantly lower than saline in all three treatment groups, while alpha-smooth muscle actin was significantly reduced only with high-dose liraglutide. These findings identify liraglutide as a candidate antifibrotic approach for adhesive capsulitis warranting further preclinical and clinical investigation.