Combination therapy with SGLT2is + GLP-1RAs can address multiple components of the ominous octet (insulin and glucagon secretion, hepatic glucose production, gastrointestinal incretin defect, appetite and weight loss, and muscle and hepatic insulin sensitivity), improve cardiovascular risk, and prevent diabetic nephropathy and should therefore be considered as an option during the early treatment stages of patients with T2DM. This evidence concerns the gene INS and type 2 diabetes mellitus.