Leptin, ghrelin, and the weight paradox of sodium-glucose cotransporter 2 (SGLT2) inhibition: a new piece of an old puzzle

Cardiovascular disease is a leading cause of global mortality, necessitating effective strategies for prevention and treatment.The cardiovascular disease continuum concept highlights the progression from risk factors such as hypertension and diabetes mellitus to advanced stages, including heart failure (HF) and death.Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed to manage diabetes, have emerged as effective therapies across all stages of the cardiovascular disease continuum.Numerous cardiovascular outcome trials demonstrate that SGLT2 inhibitors significantly reduce major adverse cardiovascular events and hospitalizations for HF in patients with and without established atherosclerotic cardiovascular disease.Notably, SGLT2 inhibitors have shown remarkable benefits in reducing HF risk, even in patients without diabetes, including those with HF and preserved ejection fraction.Furthermore, recent studies in post-myocardial infarction patients suggest potential benefits in reducing hospitalizations for HF.Despite their widespread use, the precise mechanisms by which SGLT2 inhibitors confer cardiovascular protection remain unclear, suggesting the need for further investigation.In conclusion, SGLT2 inhibitors have revolutionized cardiovascular disease management, offering significant therapeutic potential across a broad spectrum of patients, and are expected to play an increasingly prominent role in both the prevention and treatment of cardiovascular disease.