Here, we found that the plasma GLP-1 levels were reduced, and liraglutide, a long-acting GLP-1 analog, inhibited osteogenic differentiation and inflammation, reducing the aortic valve leaflet thickness and collagen and calcium deposition, an effect eventually resulting in attenuated aortic valve stenosis in an HCD-induced experimental CAVD model in Apoe−/− mice. This evidence concerns the gene GCG and heavy chain disease.