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Metabolism of the failing heart and the impact of SGLT2 inhibitors

ABSTRACT Introduction: Cardiac metabolism represents a complex network of numerous pathways responsible for an adequate supply of ATP to the incessant contractile apparatus. Impairments of such pathways are associated with myocardial dysfunction. The newest antidiabetic drugs, the SGLT2 inhibitors, have been demonstrated to reduce cardiovascular mortality and heart failure hospitalizations. The mechanisms underlying these benefits are still uncertain; however, they may play a decisive role in restoring energy efficiency to the damaged heart. Areas covered: This article reviews normal cardiac metabolism and contribution of different substrates to fuel supply. Specific attention is devoted to alterations of these pathways and their association with myocardial dysfunction. In addition, the impact of the novel SGLT2 inhibitors on cardiac mortality and heart failure hospitalizations is discussed. Various postulated mechanisms responsible for such benefits are also discussed. Expert opinion: Metabolic alterations seem to play a crucial role in etiology and progression of heart failure. The cardiovascular benefits of the novel SGLT2 inhibitors have attracted more attention to this field. With effects beyond lowering glucose levels, these agents have been reported to induce changes in cardiac metabolism and to exert anti-inflammatory properties that may contribute to their large cardiovascular beneficial effects by improving contractile bioenergetics. Therefore, SGLT2 inhibitors may become an alternative drug to treat heart failure patients, regardless of diabetic status.