Sodium-Glucose Co-transporter 2 Inhibitors in the Failing Heart: a Growing Potential

Abstract

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new drug class designed to treat patients with type 2 diabetes (T2D). However, cardiovascular outcome trials showed that SGLT2i also offer protection against heart failure (HF)–related events and cardiovascular mortality. These benefits appear to be independent of glycaemic control and have recently been demonstrated in the HF population with reduced ejection fraction (HFrEF), with or without T2D. This comprehensive, evidence-based review focuses on the published studies concerning HF outcomes with SGLT2i, discussing issues that may underlie the different results, along with the impact of these new drugs in clinical practice. The potential translational mechanisms behind SGLT2i cardio-renal benefits and the information that ongoing studies may add to the already existing body of evidence are also reviewed. Finally, we focus on practical management issues regarding SGLT2i use in association with other T2D and HFrEF common pharmacological therapies. Safety considerations are also highlighted. Considering the paradigm shift in T2D management, from a focus on glycaemic control to a broader approach on cardiovascular protection and event reduction, including the potential for wide SGLT2i implementation in HF patients, with or without T2D, we are facing a promising time for major changes in the global management of cardiovascular disease.

Sodium–Glucose Cotransporter 2 Inhibitors in Heart Failure with Preserved Ejection Fraction: Rationale for and Practical Use of a Successful Therapy

“…These important characteristics explain why they have been named the ‘smartest diuretics’. [ 35 ] However there are some caveats when using them.…”

Emergence of SGLT2 Inhibitors as Powerful Antioxidants in Human Diseases

“…Several mechanisms have been proposed for the cardiovascular effects of SGLT2 inhibitors, including reduced blood pressure, cardiac preload and afterload, plasma volume, increased hematocrit, increased myocardial energetic efficiency, inhibition of Na + /H + exchanger (NHE), and decreased oxidative stress [ 1 , 20 , 110 ]. This review highlights the potential antioxidant effects of SGLT2 inhibitors in heart failure.…”

Gliflozinas: más que antidiabéticos orales. Una breve revisión de la literatura

“…Asimismo, si bien el aumento del hematocrito observado se explica por hemoconcentración, también se debe a que la disminución de la congestión renal disminuye el estrés parietal y la isquemia mejorando la función de las células yuxtaglomerulares encargadas de secretar eritropoyetina. Por último, al provocar glucosuria, generan disminución de la glucotoxicidad (32)(33)(34)(35)(36) .…”

“…En última instancia, el aumento del Ca intracelular genera fibrosis e hipertrofia mediadas por la calcineurina. Este mecanismo se ha propuesto para ex-plicar la cardiotoxicidad, la nefrotoxicidad y la resistencia a los diuréticos en la IC (34)(35)(36)(37)(38)(39) . Recientemente se ha publicado un trabajo experimental realizado con miocitos de ratas que pone en duda la acción de la empagliflozina sobre el intercambiador NHE1.…”