CVOTs have notably clearly established the CV safety or even the benefit of two therapeutic classes, Glucagon-Like Peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i), and have positioned them as priority options in the management of type 2 diabetes, especially in patients with an established CV disease, heart failure and/or chronic kidney disease. The gene discussed is GLP1R; the disease is type 2 diabetes mellitus.