SGLT2 inhibitors, GLP-1RAs, metformin, and DPP-4 inhibitors converge on AMPK activation and NF-κB suppression while enhancing Nrf2-mediated antioxidant defenses, thereby reducing vascular ROS, attenuating cytokine-driven fibrosis, and contributing to the reductions in heart failure events seen in clinical trials. This evidence concerns the gene SLC5A2 and heart failure.