University of Toronto researchers found that semaglutide improves liver health through a direct mechanism on liver cells, independent of weight loss—a finding that challenges the assumption that GLP-1 drugs only help livers by triggering weight reduction. The discovery matters because it means physicians could prescribe lower doses to achieve liver benefits without side effects from higher weight-loss doses, potentially reducing costs and expanding who can safely benefit from these drugs. The research used sophisticated mouse models and gene analysis to identify that liver sinusoidal endothelial cells (LSECs) carry GLP-1 receptors and respond by releasing anti-inflammatory molecules—overturning the longstanding belief that liver cells don't have these receptors at all.