Am J Med. 2023 May 7:S0002-9343(23)00298-X. doi: 10.1016/j.amjmed.2023.04.035. Online ahead of print.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as an important approach for the treatment of heart failure in patients with or without diabetes. Although the precise mechanisms underpinning their clinical impact remain incompletely resolved, mechanistic studies and insights from major cardiovascular outcomes trials have shown that SGLT2 inhibitors modulate various cardio-renal-metabolic pathways. Heart failure with preserved ejection fraction (HFpEF), representing approximately half of all patients with heart failure, has been described as the greatest unmet need in cardiovascular medicine. Despite rates of morbidity and mortality that are commensurate with those of heart failure with reduced ejection fraction (HFrEF), disease-modifying therapies are severely lacking. Within the past decade, HFpEF has been established as a highly integrated and multiorgan disorder, involving not only the cardiovascular system, but also the lungs, kidneys, skeletal muscle, and adipose tissue. Given their multisystem impact, SGLT2 inhibitors offer unique promise in addressing the complex pathophysiology of HFpEF, and in one recent randomized controlled trial, were shown to significantly reduce the risk of the composite of cardiovascular death or heart failure hospitalization in patients with HFpEF. Herein, we discuss several proposed mechanisms of clinical benefit of SGLT2 inhibitors in heart failure overall, as well as highlight the mechanistic potential of SGLT2 inhibition in HFpEF with a view toward forthcoming clinical trials.
PMID:37160196 | DOI:10.1016/j.amjmed.2023.04.035