This meta-analysis, including six large trials of four kinds of SGLT2 inhibitors in HFpEF and HFmrEF, showed that the SGLT2 inhibitors robustly reduced the composite of cardiovascular death or hospitalization for heart failure, supporting their beneficial effects as a foundational therapy for patients with HFpEF or HFmrEF. This evidence concerns the gene SLC5A2 and heart failure.