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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Bibliographic Details
Published in:Diabetologia Vol. 61; no. 10; pp. 2108 - 2117
Main Authors: Verma, Subodh, McMurray, John J. V.
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2018
Springer Nature B.V
Subjects:
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
Online Access:Get full text
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Summary: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.
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ISSN:0012-186X
1432-0428
1432-0428
DOI:10.1007/s00125-018-4670-7