A comprehensive Review of Preclinical and Clinical Information on the Cardiovascular Advantages of SGLT2 Inhibitors

Diabetes, a leading cause of morbidity and mortality worldwide, poses cardiovascular risks that some anti-diabetic medications may exacerbate. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated protective cardiovascular effects in both diabetic and non-diabetic patients. Research shows that SGLT2i can reverse adverse cardiac remodeling—characterized by hypertrophy, fibrosis, and inflammation—in preclinical and clinical settings. In heart failure (HF) patients, SGLT2i therapy is thought to shift cardiac metabolism toward ketone oxidation, increasing energy efficiency. Notable clinical trials, including EMPA-REG OUTCOME, DAPA-HF, and EMPEROR-REDUCED, highlight SGLT2i’s effectiveness in reducing cardiovascular mortality and hospitalizations, benefiting patients regardless of diabetes status. Further studies underscore SGLT2i’s role in decreasing left ventricular mass, improving cardiac function, and lowering inflammatory markers. This therapy, now recognized as a first-line treatment for HF and chronic kidney disease in diabetes, continues to undergo trials to expand its clinical applications and clarify its diverse cardioprotective mechanisms.