The results of McLean et al. show that semaglutide decreases atherosclerosis in mice, regardless of GLP-1 receptor expression on Tie2+ endothelial cells and hematopoietic cells, suggesting that the vascular protective effects of semaglutide are to mediated a great extent by positive systemic metabolic effects, e.g., reductions in glucose, lipid toxicity, and inflammation, but not via endothelial GLP-1R signaling. The gene discussed is GLP1R; the disease is atherosclerosis.