The Role of SGLT2-Inhibitors Across All Stages of Heart Failure and Mechanisms of Early Clinical Benefit: From Prevention to Advanced Heart Failure

Sodium-glucose cotransporter-2 inhibitors (SGLT2i), initially developed as antihyperglycemic agents, have revolutionized heart failure (HF) management, offering substantial benefits across all stages and phenotypes of the disease. Regardless of left ventricular ejection fraction (LVEF), these agents...

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Main Authors: Simone Pasquale Crispino, Andrea Segreti, Vincenzo Nafisio, Daniele Valente, Filippo Crisci, Aurora Ferro, Ilaria Cavallari, Annunziata Nusca, Gian Paolo Ussia, Francesco Grigioni
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Language:English
Published: MDPI AG 2025-03-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/3/608
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author Simone Pasquale Crispino
Andrea Segreti
Vincenzo Nafisio
Daniele Valente
Filippo Crisci
Aurora Ferro
Ilaria Cavallari
Annunziata Nusca
Gian Paolo Ussia
Francesco Grigioni
author_facet Simone Pasquale Crispino
Andrea Segreti
Vincenzo Nafisio
Daniele Valente
Filippo Crisci
Aurora Ferro
Ilaria Cavallari
Annunziata Nusca
Gian Paolo Ussia
Francesco Grigioni
author_sort Simone Pasquale Crispino
collection DOAJ
description Sodium-glucose cotransporter-2 inhibitors (SGLT2i), initially developed as antihyperglycemic agents, have revolutionized heart failure (HF) management, offering substantial benefits across all stages and phenotypes of the disease. Regardless of left ventricular ejection fraction (LVEF), these agents have proven efficacy in both chronic and acute HF presentations. This review explores SGLT2i applications spanning the HF continuum, from early stages (Stage A) in at-risk individuals to the mitigation of progression in advanced HF (Stage D). Evidence from numerous trials has shown that SGLT2i significantly lower rates of HF hospitalization, improve renal function, and decreases cardiovascular mortality, highlighting their multifaced mechanisms of action in HF care. This review also highlights the potential mechanisms by which SGLT2i exert their beneficial effects on the cardiovascular and renal systems, each contributing to early and sustained clinical improvements. However, the integration of SGLT2i into guideline-directed medical therapy poses practical challenges, including initiation timing, dosing, and monitoring, which are addressed to support effective treatment adaptation across patient populations. Ultimately, this review provides a comprehensive assessment of SGLT2i as a foundational therapy in HF, emphasizing their role as an intervention across multiple stages aimed at improving outcomes across the entire HF spectrum.
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spelling doaj-art-2df13a3b68e9400f9363fc785b8151bc2025-08-20T02:42:35ZengMDPI AGBiomedicines2227-90592025-03-0113360810.3390/biomedicines13030608The Role of SGLT2-Inhibitors Across All Stages of Heart Failure and Mechanisms of Early Clinical Benefit: From Prevention to Advanced Heart FailureSimone Pasquale Crispino0Andrea Segreti1Vincenzo Nafisio2Daniele Valente3Filippo Crisci4Aurora Ferro5Ilaria Cavallari6Annunziata Nusca7Gian Paolo Ussia8Francesco Grigioni9Department of Cardiovascular Sciences, Fondazione Policlinico Campus Bio-Medico di Roma, 00128 Rome, ItalyDepartment of Cardiovascular Sciences, Fondazione Policlinico Campus Bio-Medico di Roma, 00128 Rome, ItalyDepartment of Cardiovascular Sciences, Fondazione Policlinico Campus Bio-Medico di Roma, 00128 Rome, ItalyDepartment of Cardiovascular Sciences, Fondazione Policlinico Campus Bio-Medico di Roma, 00128 Rome, ItalyDepartment of Cardiovascular Sciences, Fondazione Policlinico Campus Bio-Medico di Roma, 00128 Rome, ItalyDepartment of Cardiovascular Sciences, Fondazione Policlinico Campus Bio-Medico di Roma, 00128 Rome, ItalyDepartment of Cardiovascular Sciences, Fondazione Policlinico Campus Bio-Medico di Roma, 00128 Rome, ItalyDepartment of Cardiovascular Sciences, Fondazione Policlinico Campus Bio-Medico di Roma, 00128 Rome, ItalyDepartment of Cardiovascular Sciences, Fondazione Policlinico Campus Bio-Medico di Roma, 00128 Rome, ItalyDepartment of Cardiovascular Sciences, Fondazione Policlinico Campus Bio-Medico di Roma, 00128 Rome, ItalySodium-glucose cotransporter-2 inhibitors (SGLT2i), initially developed as antihyperglycemic agents, have revolutionized heart failure (HF) management, offering substantial benefits across all stages and phenotypes of the disease. Regardless of left ventricular ejection fraction (LVEF), these agents have proven efficacy in both chronic and acute HF presentations. This review explores SGLT2i applications spanning the HF continuum, from early stages (Stage A) in at-risk individuals to the mitigation of progression in advanced HF (Stage D). Evidence from numerous trials has shown that SGLT2i significantly lower rates of HF hospitalization, improve renal function, and decreases cardiovascular mortality, highlighting their multifaced mechanisms of action in HF care. This review also highlights the potential mechanisms by which SGLT2i exert their beneficial effects on the cardiovascular and renal systems, each contributing to early and sustained clinical improvements. However, the integration of SGLT2i into guideline-directed medical therapy poses practical challenges, including initiation timing, dosing, and monitoring, which are addressed to support effective treatment adaptation across patient populations. Ultimately, this review provides a comprehensive assessment of SGLT2i as a foundational therapy in HF, emphasizing their role as an intervention across multiple stages aimed at improving outcomes across the entire HF spectrum.https://www.mdpi.com/2227-9059/13/3/608acute heart failure (AHF)chronic heart failure (CHF)four pillarsfoundational therapyGDMTheart failure (HF)
spellingShingle Simone Pasquale Crispino
Andrea Segreti
Vincenzo Nafisio
Daniele Valente
Filippo Crisci
Aurora Ferro
Ilaria Cavallari
Annunziata Nusca
Gian Paolo Ussia
Francesco Grigioni
The Role of SGLT2-Inhibitors Across All Stages of Heart Failure and Mechanisms of Early Clinical Benefit: From Prevention to Advanced Heart Failure
Biomedicines
acute heart failure (AHF)
chronic heart failure (CHF)
four pillars
foundational therapy
GDMT
heart failure (HF)
title The Role of SGLT2-Inhibitors Across All Stages of Heart Failure and Mechanisms of Early Clinical Benefit: From Prevention to Advanced Heart Failure
title_full The Role of SGLT2-Inhibitors Across All Stages of Heart Failure and Mechanisms of Early Clinical Benefit: From Prevention to Advanced Heart Failure
title_fullStr The Role of SGLT2-Inhibitors Across All Stages of Heart Failure and Mechanisms of Early Clinical Benefit: From Prevention to Advanced Heart Failure
title_full_unstemmed The Role of SGLT2-Inhibitors Across All Stages of Heart Failure and Mechanisms of Early Clinical Benefit: From Prevention to Advanced Heart Failure
title_short The Role of SGLT2-Inhibitors Across All Stages of Heart Failure and Mechanisms of Early Clinical Benefit: From Prevention to Advanced Heart Failure
title_sort role of sglt2 inhibitors across all stages of heart failure and mechanisms of early clinical benefit from prevention to advanced heart failure
topic acute heart failure (AHF)
chronic heart failure (CHF)
four pillars
foundational therapy
GDMT
heart failure (HF)
url https://www.mdpi.com/2227-9059/13/3/608
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