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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Vydané v:	Diabetologia Ročník 61; číslo 10; s. 2108 - 2117
Hlavní autori:	Verma, Subodh, McMurray, John J. V.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2018 Springer Nature B.V
Predmet:	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
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Literature Review-3 ObjectType-Review-3 content type line 23
ISSN:	0012-186X 1432-0428 1432-0428
DOI:	10.1007/s00125-018-4670-7