Taken together, these data demonstrate that hyperinsulinemia per se promotes breast cancer progression in obese mice, and recommend clinical studies investigating the potential utility of insulin-lowering agents including SGLT2 inhibitors and insulin-sensitizing mitochondrial protonophores currently under development as a means of slowing obesity-associated breast tumor growth. This evidence concerns the gene SLC5A2 and obesity due to melanocortin 4 receptor deficiency.