TLR4 and hyperinsulinism: By improving insulin sensitivity, GLP-1RAs reduce hyperinsulinemia, a key driver of lymphatic vessel dysfunction.52 Mechanistically, GLP-1RAs activate GLP-1 receptors on LECs, promoting lymphangiogenesis and lymphatic vessel repair via nitric oxide (NO) production through eNOS and suppression of ROS.53 Additionally, GLP-1RAs downregulate pro-inflammatory cytokines and TLR signaling, particularly TLR4, reducing lymphatic inflammation and preventing fibrosis.54