GLP-1 receptor agonist liraglutide facilitates rotator cuff healing by reducing tendon cell inflammation and endoplasmic reticulum stress through the GLP-1R-AMPK/SIRT1 pathway.

Rotator cuff injuries are a common cause of shoulder pain with limited treatment options. Recent studies highlight inflammation's role in tendinopathy. GLP-1R agonists have shown anti-inflammatory effects in various diseases, but their role in rotator cuff injuries is unclear. This study investigates Liraglutide's (LIRA) effects on tendon cell inflammation, apoptosis, and endoplasmic reticulum stress in vitro and its therapeutic effects on rat rotator cuff repair in vivo. LIRA significantly inhibits IL-1β-induced inflammation, enhances tendon cell anabolism, and upregulates the AMPK/SIRT1 pathway. Mechanistically, GLP-1R interacts with SIRT1 to prevent tendon cell apoptosis and endoplasmic reticulum stress. LIRA effectively promotes tissue regeneration and restores biomechanical strength in a rat rotator cuff injury model. These findings suggest LIRA's therapeutic potential for rotator cuff repair and highlight GLP-1R activation as a key mechanism.