SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review

Sodium–glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. Here, we review the proposed mechanistic underpinnings of this benefit. Specifically, we focus on the role of SGLT2 inhibitors in opti...

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Vydáno v:	Diabetologia Ročník 61; číslo 10; s. 2108 - 2117
Hlavní autoři:	Verma, Subodh, McMurray, John J. V.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2018 Springer Nature B.V
Témata:	Adipokines - metabolism Animals Benzhydryl Compounds - pharmacology Blood Glucose - metabolism Cardiovascular Diseases - complications Cardiovascular Diseases - drug therapy Diabetes Complications - complications Diabetes Complications - drug therapy Diabetes mellitus Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Diuresis Glucosides - pharmacology Heart - drug effects Heart diseases Heart failure Heart Ventricles - drug effects Heart Ventricles - pathology Human Physiology Humans Hypoglycemic Agents - pharmacology Internal Medicine Kidney - drug effects Medicine Medicine & Public Health Metabolic Diseases Na+/glucose cotransporter Na+/H+-exchanging ATPase Review Sodium Sodium-Glucose Transporter 2 Inhibitors - pharmacology Structure-function relationships Ventricle Heart failure Mechanisms Review Cardiovascular effects SGLT2 inhibitors
ISSN:	0012-186X, 1432-0428, 1432-0428
On-line přístup:	Získat plný text
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Abstract	Sodium–glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. Here, we review the proposed mechanistic underpinnings of this benefit. Specifically, we focus on the role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function. Further insights into the role of SGLT2 inhibition in myocardial metabolism and substrate utilisation are outlined. Finally, we discuss two emerging themes: how SGLT2 inhibitors may regulate Na + /H + exchange at the level of the heart and kidney and how they may modulate adipokine production. The mechanistic discussion is placed in the context of completed and ongoing trials of SGLT2 inhibitors in the prevention and treatment of heart failure in individuals with and without diabetes.
AbstractList	Sodium-glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. Here, we review the proposed mechanistic underpinnings of this benefit. Specifically, we focus on the role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function. Further insights into the role of SGLT2 inhibition in myocardial metabolism and substrate utilisation are outlined. Finally, we discuss two emerging themes: how SGLT2 inhibitors may regulate Na /H exchange at the level of the heart and kidney and how they may modulate adipokine production. The mechanistic discussion is placed in the context of completed and ongoing trials of SGLT2 inhibitors in the prevention and treatment of heart failure in individuals with and without diabetes. Sodium–glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. Here, we review the proposed mechanistic underpinnings of this benefit. Specifically, we focus on the role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function. Further insights into the role of SGLT2 inhibition in myocardial metabolism and substrate utilisation are outlined. Finally, we discuss two emerging themes: how SGLT2 inhibitors may regulate Na+/H+ exchange at the level of the heart and kidney and how they may modulate adipokine production. The mechanistic discussion is placed in the context of completed and ongoing trials of SGLT2 inhibitors in the prevention and treatment of heart failure in individuals with and without diabetes. Sodium-glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. Here, we review the proposed mechanistic underpinnings of this benefit. Specifically, we focus on the role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function. Further insights into the role of SGLT2 inhibition in myocardial metabolism and substrate utilisation are outlined. Finally, we discuss two emerging themes: how SGLT2 inhibitors may regulate Na+/H+ exchange at the level of the heart and kidney and how they may modulate adipokine production. The mechanistic discussion is placed in the context of completed and ongoing trials of SGLT2 inhibitors in the prevention and treatment of heart failure in individuals with and without diabetes.Sodium-glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. Here, we review the proposed mechanistic underpinnings of this benefit. Specifically, we focus on the role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function. Further insights into the role of SGLT2 inhibition in myocardial metabolism and substrate utilisation are outlined. Finally, we discuss two emerging themes: how SGLT2 inhibitors may regulate Na+/H+ exchange at the level of the heart and kidney and how they may modulate adipokine production. The mechanistic discussion is placed in the context of completed and ongoing trials of SGLT2 inhibitors in the prevention and treatment of heart failure in individuals with and without diabetes. Sodium–glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. Here, we review the proposed mechanistic underpinnings of this benefit. Specifically, we focus on the role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function. Further insights into the role of SGLT2 inhibition in myocardial metabolism and substrate utilisation are outlined. Finally, we discuss two emerging themes: how SGLT2 inhibitors may regulate Na + /H + exchange at the level of the heart and kidney and how they may modulate adipokine production. The mechanistic discussion is placed in the context of completed and ongoing trials of SGLT2 inhibitors in the prevention and treatment of heart failure in individuals with and without diabetes.
Author	Verma, Subodh McMurray, John J. V.
Author_xml	– sequence: 1 givenname: Subodh surname: Verma fullname: Verma, Subodh email: vermasu@smh.ca organization: Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael’s Hospital, University of Toronto – sequence: 2 givenname: John J. V. surname: McMurray fullname: McMurray, John J. V. organization: British Heart Foundation, Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/30132036$$D View this record in MEDLINE/PubMed
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Copyright	Springer-Verlag GmbH Germany, part of Springer Nature 2018 Diabetologia is a copyright of Springer, (2018). All Rights Reserved.
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Snippet	Sodium–glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome... Sodium-glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome...
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SubjectTerms	Adipokines - metabolism Animals Benzhydryl Compounds - pharmacology Blood Glucose - metabolism Cardiovascular Diseases - complications Cardiovascular Diseases - drug therapy Diabetes Complications - complications Diabetes Complications - drug therapy Diabetes mellitus Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Diuresis Glucosides - pharmacology Heart - drug effects Heart diseases Heart failure Heart Ventricles - drug effects Heart Ventricles - pathology Human Physiology Humans Hypoglycemic Agents - pharmacology Internal Medicine Kidney - drug effects Medicine Medicine & Public Health Metabolic Diseases Na+/glucose cotransporter Na+/H+-exchanging ATPase Review Sodium Sodium-Glucose Transporter 2 Inhibitors - pharmacology Structure-function relationships Ventricle
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Title	SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review
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