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However, cardiovascular outcome trials showed that SGLT2i also offer protection against heart failure (HF)\u2013related 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.<\/jats:p>","DOI":"10.1007\/s10557-020-06973-3","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T04:06:08Z","timestamp":1588219568000},"page":"419-436","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Sodium-Glucose Co-transporter 2 Inhibitors in the Failing Heart: a Growing Potential"],"prefix":"10.1007","volume":"34","author":[{"given":"Dulce","family":"Brito","sequence":"first","affiliation":[]},{"given":"Paulo","family":"Bettencourt","sequence":"additional","affiliation":[]},{"given":"Davide","family":"Carvalho","sequence":"additional","affiliation":[]},{"given":"Jorge","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"Ricardo","family":"Fontes-Carvalho","sequence":"additional","affiliation":[]},{"given":"F\u00e1tima","family":"Franco","sequence":"additional","affiliation":[]},{"given":"Brenda","family":"Moura","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 Carlos","family":"Silva-Cardoso","sequence":"additional","affiliation":[]},{"given":"Rachel Tavares","family":"de Melo","sequence":"additional","affiliation":[]},{"given":"C\u00e2ndida","family":"Fonseca","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,4,30]]},"reference":[{"key":"6973_CR1","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","volume":"37","author":"P Ponikowski","year":"2016","unstructured":"Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. 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