New antidiabetic therapy that includes sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors showed significant benefit on cardiovascular outcomes in patients with and without type 2 diabetes mellitus, and this was particularly confirmed for SGLT2 inhibitors in subjects with heart failure (HF) with reduced ejection fraction (HFrEF). This evidence concerns the gene GLP1R and heart failure.