The U.S. Centers for Disease Control have highlighted 13 tumor types in which obesity confers and increased risk and poorer prognosis. Since the work of Warburg, it has been known that tumors are addicted to glucose. Unfortunately, most trials of common metabolism-targeting drugs – primarily metformin – have failed to show any benefit. We have shown, however, that a drug that has a larger impact on the glucose and insulin areas under the curve throughout the day – namely, the SGLT2 inhibitor dapagliflozin – may be more effective than metformin. In this talk, we will show data from our group demonstrating that both as monotherapy and in combination with chemotherapy, dapagliflozin slows tumor growth in murine models of colon and breast cancer. We find a mutational signature for which tumors will respond to dapagliflozin therapy: namely, tumors driven by mutations upstream of the canonical insulin signaling pathway respond to dapagliflozin in combination with chemotherapy, while tumors driven by mutations outside of or downstream of the canonical insulin signaling pathway do not. These studies support the development of precision medicine approaches to metabolic therapy for obesity-related cancers.