May 7, 2023Open Access
Chapter 2: Clinical and Mechanistic Potential of Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors in Heart Failure with Preserved Ejection Fraction
Key Result
SGLT2 inhibitors significantly reduce heart failure events and cardiovascular death in patients with HFpEF through their impact on numerous cardio-renal-metabolic pathways.
Structured PICO
Do SGLT2 inhibitors improve clinical outcomes in patients with heart failure with preserved ejection fraction?
P
Population
Patients with heart failure with preserved ejection fraction (HFpEF)
I
Intervention
Sodium-glucose co-transporter 2 inhibitors (SGLT2i)
SGLT2 inhibitors offer unique promise in addressing the complex multisystem pathophysiology of HFpEF, reducing heart failure events and cardiovascular death.
Abstract
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) 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 clinical trials have demonstrated the impact of SGLT2 inhibitors on numerous cardio-renal-metabolic pathways of relevance to heart failure with preserved ejection fraction (HFpEF), which, in the contemporary era, constitutes approximately half of all patients with heart failure. Despite rates of morbidity and mortality that are commensurate with those of heart failure with reduced ejection fraction, disease-modifying therapies have comparatively been severely lacking. As such, HFpEF remains among the greatest unmet needs in cardiovascular medicine. Within the past decade, HFpEF has been established as a highly integrated disorder, involving not only the cardiovascular system, but also the lungs, kidneys, skeletal muscle, and adipose tissue. Given their multisystem impact, SGLT2i offer unique promise in addressing the complex pathophysiology of HFpEF, and in recent randomized controlled trials, were shown to significantly reduce heart failure events and cardiovascular death in patients with HFpEF. Herein, we discuss several proposed mechanisms of clinical benefit of SGLT2i in HFpEF.