Herein, we examined the effect of liraglutide on aortic valve stenosis using a high-cholesterol-diet-induced experimental CAVD model in apolipoprotein E-deficient (Apoe−/−) mice and found that liraglutide blocks aortic valve stenosis through attenuating aortic valve inflammation, VIC osteogenic differentiation, and calcification. Here, APOE is linked to congenital bilateral aplasia of vas deferens from CFTR mutation.