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Remarkably, sodium\u2013glucose cotransporter 2 inhibitors (SGLT2is) may be the first drug class to improve cardiovascular outcomes in HFpEF. Randomised controlled trials suggest a benefit in mortality, and demonstrate decreased hospitalisations and improvement in functional status. Limitations in trials exist, either due to small sample sizes, differing results between trials or decreased efficacy at higher ejection fractions. SGLT2is may provide a class effect by targeting various pathophysiological HFpEF mechanisms. Inhibition of SGLT2 and Na+\/H+ exchanger 3 in the kidney promotes glycosuria, osmotic diuresis and natriuresis. The glucose deprivation activates sirtuins \u2013 protecting against oxidation and beneficially regulating metabolism. SGLT2is reduce excess epicardial adipose tissue and its deleterious adipokines. Na+\/H+ exchanger 1 inhibition in the heart and lungs reduces sodium-induced calcium overload and pulmonary hypertension, respectively.<\/jats:p>","DOI":"10.15420\/cfr.2022.11","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T13:30:54Z","timestamp":1656509454000},"source":"Crossref","is-referenced-by-count":31,"title":["Clinical Evidence and Proposed Mechanisms of Sodium\u2013Glucose Cotransporter\u00a02 Inhibitors in Heart Failure with Preserved Ejection Fraction: A Class Effect?"],"prefix":"10.15420","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4097-4681","authenticated-orcid":false,"given":"Brent","family":"Deschaine","sequence":"first","affiliation":[{"name":"University of Florida College of Medicine, Gainesville, FL, US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9401-6809","authenticated-orcid":false,"given":"Sahil","family":"Verma","sequence":"additional","affiliation":[{"name":"Florida State University College of Medicine, Tallahassee, FL, US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8855-1306","authenticated-orcid":false,"given":"Hussein","family":"Rayatzadeh","sequence":"additional","affiliation":[{"name":"Florida State University College of Medicine, Tallahassee, FL, US; Tallahassee Research Institute, Tallahassee, FL, US; Southern Medical Group, Tallahassee, FL, US"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6096","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"Bhatt DL, Szarek M, Steg PG, et al. 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