Randomized CVOTs in diabetes support a consistent reduction in HF events with SGLT2 inhibitors across risk strata, reinforcing the concept that diabetes both increases HF risk and offers a therapeutic target that modifies prognosis; however, many RCT populations were enriched for established cardiovascular disease, and observational data are subject to confounding, so absolute generalizability remains constrained [88, 111, 145]. This evidence concerns the gene SLC5A2 and diabetes mellitus.