Two types of non-insulin glucose-lowering drugs (GLD: sodium glucose co-transporter 2 [SGLT-2] inhibitors and glucagon-like peptide 1 [GLP-1] analogues; collectively, cardioprotective GLDs), substantially reduce the risk of cardiovascular events and hospitalization for heart failure in T2DM patients with established CVD (ischemic heart disease, heart failure, peripheral heart disease or stroke) in clinical trials [5–11] and in real-world settings [12, 13]. This evidence concerns the gene GCG and heart failure.