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ABSTRACTIntroduction: 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.

ABSTRACTIntroduction: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder associated with high cardiovascular (CV) risk. Some of the therapeutic strategies are contraindicated in patients with concomitant heart disease. However, the newest antidiabetic medications, sodium-glucose cotransporter 2 (SGLT2) inhibitors, have shown to significantly reduce CV mortality and heart failure (HF) hospitalizations. The mechanism behind these surprising cardiac benefits remains unclear.Areas covered: This article reviews the pharmacokinetic, pharmacodynamics, efficacy, and safety data for the different SGLT2 inhibitors. Specific attention is devoted to the postulated mechanisms of action for their benefit. The therapeutic efficacy and potential use in different indications outside T2DM such as HF, T1DM, and renal disease are also discussed.Expert opinion: SGLT2 inhibitors have an excellent pharmacokinetic and pharmacodynamic profile. Importantly, SGLT2 inhibitors are a safe and efficacious treatment option for T2DM. Given their cardiac benefits (reduction in HF and death) and the low incidence of adverse events, SGLT2 inhibitors are being currently studied as a treatment for HF also in nondiabetic individuals. These agents seem to represent a shift in the treatment of HF patients regardless their glycemic profile.