Title:The Emerging Role of Sodium-glucose Cotransporter 2 Inhibitors in Heart
Failure
Volume: 29
Issue: 7
Author(s): Mauro Gitto, Alessandro Villaschi, Massimo Federici, Gianluigi Condorelli and Giulio G. Stefanini*
Affiliation:
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Biomedical Sciences, IRCCS
Humanitas Research Hospital, Rozzano-Milan, Italy
Keywords:
SGLT2 inhibitors, HFrEF, HFpEF, acute heart failure, cardiac remodeling, fluid overload.
Abstract: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively novel drug class that most cardiologists
are becoming familiar with. By contrasting glucose reabsorption in the proximal convoluted tubule of
the nephron, SGLT2 inhibition results in glycosuria with improved glycemic control. Although originally introduced
as anti-diabetic medications, the cardiovascular effects of SGLT2i have progressively emerged, leading
them to become one of the four pillars for the treatment of heart failure with reduced ejection fraction (HFrEF)
according to the 2021 guidelines from the European Society of Cardiology. Also, two recent randomized trials
have demonstrated SGLT2i as the first compounds with proven prognostic impact in heart failure with preserved
ejection fraction (HFpEF), setting a milestone in the treatment for this condition. While the exact pathogenic
mechanisms mediating the substantial reduction in cardiovascular death and heart failure (HF) hospitalizations
are still controversial, there is growing clinical evidence on the efficacy and safety of SGLT2i in various
subsets of patients with HF. As known, heart failure is a complex and heterogeneous clinical syndrome with a
magnitude of phenotypes and a variety of underlying hemodynamic and physiological aspects which cannot be
fully incorporated into the traditional left ventricular ejection fraction based classification adopted in clinical
trials. The aim of this review is to provide an overview of the cardiovascular benefits and indications of
SGLT2i across different HF patterns and to highlight current gaps in knowledge that should be addressed by future
research.
