rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2022-10-08rpcardio-2830Research ArticleCURRENT QUESTIONS OF CLINICAL PHARMACOLOGYАКТУАЛЬНЫЕ ВОПРОСЫ КЛИНИЧЕСКОЙ ФАРМАКОЛОГИИA New Chapter in the Treatment of Patients with Heart Failure. The Role of Sodium-Glucose Co-transporter Type 2 InhibitorsНовая глава в лечении пациентов с сердечной недостаточностью. Роль ингибиторов натрий-глюкозного ко-транспортера 2-го типаhttps://orcid.org/0000-0002-3922-009XГолубовскаяД. П.GolubovskayaD. P.

 Голубовская Дарья Петровна

eLibrary SPIN 1921-9600

 Кемерово 

 Daria P. Golubovskaya 

 Kemerovo 

https://orcid.org/0000-0002-9801-9839КаретниковаВ. Н.KaretnikovaV. N.

 Каретникова Виктория Николаевна

eLibrary SPIN 7952-6247

 Кемерово 

 Victoria N. Karetnikova 

 Kemerovo 

tori1071@mail.ruhttps://orcid.org/0000-0001-5470-3076ОлейникИ. Р.OleinikI. R.

 Олейник Ирина Романовна

eLibrary SPIN 3506-1898

 Кемерово 

 Irina R. Oleinik 

 Kemerovo 

https://orcid.org/0000-0002-4642-3610БарбарашО. Л.BarbarashO. L.

Барбараш Ольга Леонидовна

eLibrary SPIN 5373-7620

 Кемерово 

 Olga L. Barbarash 

 Kemerovo 

Кемеровский государственный медицинский университетРоссияKemerovo State Medical UniversityRussian FederationКемеровский государственный медицинский университет; Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеванийРоссияKemerovo State Medical University; Research Institute for Complex Problems of Cardiovascular DiseasesRussian FederationНаучно-исследовательский институт комплексных проблем сердечно-сосудистых заболеванийРоссияResearch Institute for Complex Problems of Cardiovascular DiseasesRussian Federation202206112022185606613Copyright © Golubovskaya D.P., Karetnikova V.N., Oleinik I.R., Barbarash O.L., 20222022Голубовская Д.П., Каретникова В.Н., Олейник И.Р., Барбараш О.Л.Golubovskaya D.P., Karetnikova V.N., Oleinik I.R., Barbarash O.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/2830

Heart failure (HF) remains one of the major social and medical public health problems worldwide. Despite new advances in the treatment of patients with HF, the prognosis is still poor. According to the European Cardiology Society guidelines for the diagnosis and treatment of acute and chronic heart failure (CHF) 2021, a new class of drugs related to hypoglycemic has been confirmed to be effective in influencing the survival of patients with heart failure with low ejection fraction (HFpEF), regardless of the presence of disorders of carbohydrate metabolism. We are talking about inhibitors of the sodium-glucose co-transporter type 2 (iSGLT-2) or gliflozins. The article presents the results of the latest large clinical trials on the effective use of SGLT-2 in patients with HF, not only with low, but also with intact ejection fraction (HFpEF), for which there is no evidence base at the present stage. The review article presents the results of experimental studies that explored the potential mechanisms of action of gliflozins with an emphasis on new ones that are of fundamental importance for patients with heart failure, and also describes controversial and little-studied issues. Currently, there is no therapy that improves outcomes in patients with acute heart failure. The article presents the results of small analyzes of the use of iSGLT-2 in this category of patients, which are the basis for the hypothesis of their potentially effective and safe use in the case of acute decompensation of CHF, however, the role of gliflozins in this category of patients requires further in-depth study.

Хроническая сердечная недостаточность (ХСН) остается одной из серьезных социальных и медицинских проблем общественного здравоохранения во всем мире. Несмотря на новые достижения в лечении больных ХСН, прогноз все еще остается неблагоприятным. Согласно руководству Европейского кардиологического общества по диагностике и лечению острой и хронической сердечной недостаточности 2021 г. новый класс препаратов, относящийся к сахароснижающим, подтвердил свою эффективность по влиянию на выживаемость больных сердечной недостаточностью с низкой фракцией выброса независимо от наличия нарушений углеводного обмена. Речь идет об ингибиторах натрий-глюкозного ко-транспортера 2-го типа (иНГЛТ-2) или глифлозинах. В статье приведены результаты последних крупных клинических исследований по эффективному применению иНГЛТ-2 у пациентов с ХСН не только с низкой, но и сохраненной фракцией выброса, для которых на современном этапе отсутствует доказательная база. В обзорной статье представлены результаты экспериментальных исследований, в которых изучались потенциальные механизмы действия глифлозинов с акцентом на новых, имеющих принципиальное значение для больных ХСН, а также описаны спорные и малоизученные вопросы. В настоящее время не существует терапии, которая бы улучшала исходы у пациентов с острой сердечной недостаточностью. В статье представлены результаты небольших анализов применения иНГЛТ-2 у данной категории пациентов, являющихся основой гипотезы о потенциально эффективном и безопасном их использовании в случае острой декомпенсации ХСН, однако роль глифлозинов у данной категории пациентов требует дальнейшего глубокого изучения.

ингибитор натрий-глюкозного ко-транспортера 2-го типаглифлозинысердечная недостаточностьпотенциальные механизмыэффектыпрогнозsodium-glucose co-transporter type 2 inhibitorgliflozinsheart failurepotential mechanismseffectsprognosisReferencesAmbrosy AP, Fonarow GC, Butler J, et al. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol. 2014;63(12):1123-33. DOI:10.1016/j.jacc.2013.11.053.Ambrosy AP, Fonarow GC, Butler J, et al. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol. 2014;63(12):1123-33. DOI:10.1016/j.jacc.2013.11.053.Ponikowski P, Voors AA, Anker SD, et al. Authors/Task Force Members; Document Reviewers. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;37 (27):2129-200. DOI:10.1002/ejhf.592.Ponikowski P, Voors AA, Anker SD, et al. Authors/Task Force Members; Document Reviewers. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;37 (27):2129-200. DOI:10.1002/ejhf.592.Сергеева Е.М., Малишевский М.В., Васина А.А., и др. Лечение хронической сердечной недостаточности в первичном звене муниципального здравоохранения в г. Тюмени. Медицинская Наука и Образование Урала. 2015;16(4):32-4.Sergeeva EM, Malishevsky MV, Vasina AA, et al. Chronic hert failure treatment in primary municipal health services in Tyumen. Medical science and education of Ural. 2015;16(4):32-4 (In Russ.).Смирнова Е.А. Изучение распространенности и этиологии хронической сердечной недостаточности в Рязанской области. Российский Кардиологический Журнал. 2010;(2):78-83.Smirnova EA. Prevalence and etiology of chronic heart failure in Ryazan region. Russian Journal of Cardiology. 2010;(2):78-83 (In Russ.).Бабанская Е.Б., Меньшикова Л.В., Дац Л.С. Эпидемиология хронической сердечной недостаточности в городе Иркутске. Acta Biomedica Scientifica. 2012;5(1): 25-8.Babanskaya EB, Menshikova LV, Dats LS. Epidemiology of chronic heart failure in Irkutsk. Acta Biomedica Scientifica. 2012;5(1):25-8 (In Russ.).Беленков Ю.Н., Мареев В.Ю., Агеев Ф.Т. идр. Истинная распространенность ХСН в Европейской части Российской Федерации (госпитальный этап). Сердечная Недостаточность. 2011;12(2):63-8.Belenkov YuN, Mareev VYu, Ageev FT, et al. The true prevalence of CHF in the European part of the Russian Federation (hospital stage). Serdechnaya Nedostatochnost. 2011;12(2):63-8 (In Russ.).Мареев В.Ю., Фомин И.В., Агеев Ф. Т. идр. Клинические рекомендации ОССН - РКО-РНМОТ. Сердечная недостаточность: хроническая (ХСН) и острая декомпенсированная (ОДСН). Диагностика, профилактика и лечение. Кардиология. 2018;58(6S):8-158. DOI:10.18087/cardio.2475.Mareev VYu, Fomin IV, Ageev FT, et al. Russian Heart Failure Society, Russian Society of Cardiology. Russian Scientific Medical Society of Internal Medicine Guidelines for Heart failure: chronic (CHF) and acute decompensated (ADHF). Diagnosis, prevention and treatment. Kardiologiia. 2018;58(6S):8-158 (In Russ.). DOI:10.18087/cardio.2475.Zinman B, Wanner C, Lachin JM, et. al. EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-28. DOI:10.1056/NEJMoa1504720.Zinman B, Wanner C, Lachin JM, et. al. EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-28. DOI:10.1056/NEJMoa1504720.Корбут А.И., Климонтов В.В. Эмпаглифлозин: новая стратегия нефропротекции при сахарном диабете. Сахарный Диабет. 2017;20(1):75-84. DOI:10.14341/DM8005.Korbut AI, Klimontov VV. Empagliflozin: a new strategy for nephroprotection in diabetes. Diabetes Mellitus. 2017;20(1):75-84 (In Russ.). DOI:10.14341/DM8005.Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(7):644-57. DOI:10.1056/NEJMoa1611925.Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(7):644-57. DOI:10.1056/NEJMoa1611925.Neal B, Perkovic V, Matthews DR, et al. Rationale, design and baseline characteristics of the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R): A randomized, placebo-controlled trial. Diabetes Obes Metab. 2017;19(3):387-93. DOI:10.1111/dom.12829.Neal B, Perkovic V, Matthews DR, et al. Rationale, design and baseline characteristics of the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R): A randomized, placebo-controlled trial. Diabetes Obes Metab. 2017;19(3):387-93. DOI:10.1111/dom.12829.Kosiborod M, Cavender MA, Fu AZ, et al. CVD-REAL Investigators and Study Group. Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors). Circulation. 2017;136(3):249-59. DOI:10.1161/CIRCULATIONAHA.117.029190.Kosiborod M, Cavender MA, Fu AZ, et al. CVD-REAL Investigators and Study Group. Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors). Circulation. 2017;136(3):249-59. DOI:10.1161/CIRCULATIONAHA.117.029190.Packer M, Anker SD, Butler J, et al. EMPEROR-Reduced Trial Committees and Investigators. Empagliflozin in patients with heart failure, reduced ejection fraction, and volume overload: EMPEROR-Reduced trial. J Am Coll Cardiol. 2021;77:1381-92. DOI:10.1016/j.jacc.2021.01.033.Packer M, Anker SD, Butler J, et al. EMPEROR-Reduced Trial Committees and Investigators. Empagliflozin in patients with heart failure, reduced ejection fraction, and volume overload: EMPEROR-Reduced trial. J Am Coll Cardiol. 2021;77:1381-92. DOI:10.1016/j.jacc.2021.01.033.McMurray JJV, Solomon SD, Inzucchi SE, et al.; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. DOI:10.1056/NEJMoa1911303.McMurray JJV, Solomon SD, Inzucchi SE, et al.; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. DOI:10.1056/NEJMoa1911303.Cosentino F, Grant PJ, Aboyans V, et al. ESC Scientific Document Group. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41(2):255-323. DOI:10.1093/eurheartj/ ehz486.Cosentino F, Grant PJ, Aboyans V, et al. ESC Scientific Document Group. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41(2):255-323. DOI:10.1093/eurheartj/ ehz486.Коваленко Е.В., Ложкина М.В., Маркова Л.И., Арабидзе Г.Г. Новое направление медикаментозной коррекции хронической сердечной недостаточности с низкой фракцией выброса. Международный Журнал Сердца и Сосудистых Заболеваний. 2020;8(27):38-49. DOI:10.15829/2311-1623-8-27.Kovalenko EV, Lozhkina MV, Markova LI, Arabidze GG. A new direction of medical correction of chronic heart failure with low ejection fraction. International Journal of Heart and Vascular Diseases. 2020;8(27):38-49 (In Russ.). DOI:10.15829/2311-1623-8-27.Borlaug BA. Evaluation and management of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2020;17(9):559-73. DOI:10.1038/s41569-020-0363-2.Borlaug BA. Evaluation and management of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2020;17(9):559-73. DOI:10.1038/s41569-020-0363-2.Packer M, Butler J, Zannad F, et al. Effect of Empagliflozin on Worsening Heart Failure Events in Patients With Heart Failure and Preserved Ejection Fraction: EMPEROR-Preserved Trial. Circulation. 2021;144(16):1284-94. DOI:10.1161/CIRCULATIONAHA.121.056824.Packer M, Butler J, Zannad F, et al. Effect of Empagliflozin on Worsening Heart Failure Events in Patients With Heart Failure and Preserved Ejection Fraction: EMPEROR-Preserved Trial. Circulation. 2021;144(16):1284-94. DOI:10.1161/CIRCULATIONAHA.121.056824.Jensen J, Omar M, Kistorp C, et al. Effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate in patients with heart failure (Empire HF Renal): a prespecified substudy of a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2021;9:106-116. DOI:10.1016/S2213-8587(20)30382-X.Jensen J, Omar M, Kistorp C, et al. Effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate in patients with heart failure (Empire HF Renal): a prespecified substudy of a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2021;9:106-116. DOI:10.1016/S2213-8587(20)30382-X.Cherney DZ, Perkins BA, Soleymanlou N, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation.2014;129(5):587-97. DOI:10.1161/CIRCULATIONAHA.113.005081.Cherney DZ, Perkins BA, Soleymanlou N, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation.2014;129(5):587-97. DOI:10.1161/CIRCULATIONAHA.113.005081.Ott C, Jumar A, Striepe K, et al. A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation. Cardiovasc Diabetol. 2017;16(1):26. DOI:10.1186/s12933-017-0510-1.Ott C, Jumar A, Striepe K, et al. A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation. Cardiovasc Diabetol. 2017;16(1):26. DOI:10.1186/s12933-017-0510-1.Irace C, Casciaro F, Scavelli FB, et al. Empagliflozin influences blood viscosity and wall shear stress in subjects with type 2 diabetes mellitus compared with incretin-based therapy. Cardiovasc Diabetol. 2018;17(1):52. DOI:10.1186/s12933-018-0695-y.Irace C, Casciaro F, Scavelli FB, et al. Empagliflozin influences blood viscosity and wall shear stress in subjects with type 2 diabetes mellitus compared with incretin-based therapy. Cardiovasc Diabetol. 2018;17(1):52. DOI:10.1186/s12933-018-0695-y.Cherney DZ, Perkins BA, Soleymanlou N, et al. The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus. Cardiovasc Diabetol. 2014;13:28. DOI:10.1186/1475-2840-13-28.Cherney DZ, Perkins BA, Soleymanlou N, et al. The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus. Cardiovasc Diabetol. 2014;13:28. DOI:10.1186/1475-2840-13-28.Hallow KM, Helmlinger G, Greasley PJ, et al. Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes ObesMetab. 2018;20(3):479-87. DOI:10.1111/dom.13126.Hallow KM, Helmlinger G, Greasley PJ, et al. Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes ObesMetab. 2018;20(3):479-87. DOI:10.1111/dom.13126.Chilton R, Tikkanen I, Cannon CP, et al. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab. 2015;17(12): 1180-93. DOI:10.1111/dom.12572.Chilton R, Tikkanen I, Cannon CP, et al. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab. 2015;17(12): 1180-93. DOI:10.1111/dom.12572.Sano M. A new class of drugs for heart failure: SGLT2 inhibitors reduce sympathetic overactivity. J Cardiol 2018;71(5): 471-6. DOI:10.1016/j.jjcc.2017.12.004.Sano M. A new class of drugs for heart failure: SGLT2 inhibitors reduce sympathetic overactivity. J Cardiol 2018;71(5): 471-6. DOI:10.1016/j.jjcc.2017.12.004.Solini A, Giannini L, Seghieri M, et al. Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: a pilot study. Cardiovasc Diabetol. 2017;16(1):138. DOI:10.1186/s12933-017-0621-8.Solini A, Giannini L, Seghieri M, et al. Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: a pilot study. Cardiovasc Diabetol. 2017;16(1):138. DOI:10.1186/s12933-017-0621-8.Li H, Shin SE, Seo MS, et al. The antidiabetic drug dapagliflozin induces vasodilation via activation of PKG and Kv channels. Life Sci. 2018;197:46-55. DOI:10.1016/j.lfs.2018.01.032.Li H, Shin SE, Seo MS, et al. The antidiabetic drug dapagliflozin induces vasodilation via activation of PKG and Kv channels. Life Sci. 2018;197:46-55. DOI:10.1016/j.lfs.2018.01.032.Benham JL, Booth JE, Sigal RJ, et al. Systematic review and meta-analysis: SGLT2 inhibitors, blood pressure and cardiovascular outcomes. Int J Cardiol Heart Vasc. 2021;33:100725. DOI:10.1016/j.ijcha.2021.100725.Benham JL, Booth JE, Sigal RJ, et al. Systematic review and meta-analysis: SGLT2 inhibitors, blood pressure and cardiovascular outcomes. Int J Cardiol Heart Vasc. 2021;33:100725. DOI:10.1016/j.ijcha.2021.100725.Inzucchi SE, Zinman B, Fitchett D, et al. How does empagliflozin reduce cardiovascular mortality? Insights from a mediation analysis of the EMPA-REG OUTCOME trial. Diabetes Care. 2018;41:356-63. DOI:10.2337/dc17-1096.Inzucchi SE, Zinman B, Fitchett D, et al. How does empagliflozin reduce cardiovascular mortality? Insights from a mediation analysis of the EMPA-REG OUTCOME trial. Diabetes Care. 2018;41:356-63. DOI:10.2337/dc17-1096.Swedberg K, Young JB, Anand IS, et al. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med. 2013;368(13):1210-9. DOI:10.1056/NEJMoa1214865.Swedberg K, Young JB, Anand IS, et al. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med. 2013;368(13):1210-9. DOI:10.1056/NEJMoa1214865.Verma S, McMurray JJV. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018;61(10):2108-17. DOI:10.1007/s00125-018-4670-7.Verma S, McMurray JJV. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018;61(10):2108-17. DOI:10.1007/s00125-018-4670-7.Cohen ND, Gutman SJ, Briganti EM, Taylor AJ. Effects of empagliflozin treatment on cardiac function and structure in patients with type 2 diabetes: a cardiac magnetic resonance study. Intern Med J. 2019;49(8):1006-10. DOI:10.1111/imj.14260.Cohen ND, Gutman SJ, Briganti EM, Taylor AJ. Effects of empagliflozin treatment on cardiac function and structure in patients with type 2 diabetes: a cardiac magnetic resonance study. Intern Med J. 2019;49(8):1006-10. DOI:10.1111/imj.14260.Rau M, Thiele К, Korbinian Hartmann NUK, et al. Empaglifozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular flling pressure in patients with type 2 diabetes: a randomized controlled study. Rau et al. Cardiovasc Diabetol. 2021;20(1):6. DOI:10.1186/s12933-020-01175-5.Rau M, Thiele К, Korbinian Hartmann NUK, et al. Empaglifozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular flling pressure in patients with type 2 diabetes: a randomized controlled study. Rau et al. Cardiovasc Diabetol. 2021;20(1):6. DOI:10.1186/s12933-020-01175-5.Griffin M, Rao VS, Ivey-Miranda J, et al. Empagliflozin in heart failure: diuretic and cardiorenal effects. Circulation. 2020;142(11):1028-39. DOI:10.1161/CIRCULATIONAHA.120.045691.Griffin M, Rao VS, Ivey-Miranda J, et al. Empagliflozin in heart failure: diuretic and cardiorenal effects. Circulation. 2020;142(11):1028-39. DOI:10.1161/CIRCULATIONAHA.120.045691.Yasui A, Lee G, Hirase T, Kaneko T, et al. Empagliflozin induces transient diuresis without changing longterm overall fluid balance in Japanese patients with type 2 diabetes. Diabetes Ther. 2018;9(2):863-71. DOI:10.1007/s13300-018-0385-5.Yasui A, Lee G, Hirase T, Kaneko T, et al. Empagliflozin induces transient diuresis without changing longterm overall fluid balance in Japanese patients with type 2 diabetes. Diabetes Ther. 2018;9(2):863-71. DOI:10.1007/s13300-018-0385-5.Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560-72. DOI:10.1056/NEJMoa0802987.Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560-72. DOI:10.1056/NEJMoa0802987.Sato T, Aizawa Y, Yuasa S, et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc Diabetol. 2018;17(1):6. DOI:10.1186/s12933-017-0658-8.Sato T, Aizawa Y, Yuasa S, et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc Diabetol. 2018;17(1):6. DOI:10.1186/s12933-017-0658-8.Fukuda T, Bouchi R, Terashima M, et al. Ipragliflozin reduces epicardial fat accumulation in non-obese type 2 diabetic patients with visceral obesity: a pilot study. Diabetes Ther. 2017;8(4):851-61. DOI:10.1007/s13300-017-0279-y.Fukuda T, Bouchi R, Terashima M, et al. Ipragliflozin reduces epicardial fat accumulation in non-obese type 2 diabetic patients with visceral obesity: a pilot study. Diabetes Ther. 2017;8(4):851-61. DOI:10.1007/s13300-017-0279-y.Yagi S, Hirata Y, Ise T, et al. Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2017;9:78. DOI:10.1186/s13098-017-0275-4.Yagi S, Hirata Y, Ise T, et al. Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2017;9:78. DOI:10.1186/s13098-017-0275-4.Bouchi R, Terashima M, Sasahara Y, et al. Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: a pilot study. Cardiovasc Diabetol. 2017;16(1):32. DOI:10.1186/s12933-017-0516-8.Bouchi R, Terashima M, Sasahara Y, et al. Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: a pilot study. Cardiovasc Diabetol. 2017;16(1):32. DOI:10.1186/s12933-017-0516-8.Pinto L, Rados D, Remonti L. Efficacy of SGLT2 inhibitors in glycemic control, weight loss and blood pressure reduction: a systematic review and meta-analysis. Diabetol Metab Syndr. 2015;7:A58. DOI:10.1186/1758-5996-7-S1-A58.Pinto L, Rados D, Remonti L. Efficacy of SGLT2 inhibitors in glycemic control, weight loss and blood pressure reduction: a systematic review and meta-analysis. Diabetol Metab Syndr. 2015;7:A58. DOI:10.1186/1758-5996-7-S1-A58.Ramírez-Rodríguez AM, González-Ortiz M, Martínez-Abundis E. Effect of dapagliflozin on insulin secretion and insulin sensitivity in patients with prediabetes. Exp Clin Endocrinol Diabetes. 2020;128(8):506-11. DOI:10.1055/a-0664 7583.Ramírez-Rodríguez AM, González-Ortiz M, Martínez-Abundis E. Effect of dapagliflozin on insulin secretion and insulin sensitivity in patients with prediabetes. Exp Clin Endocrinol Diabetes. 2020;128(8):506-11. DOI:10.1055/a-0664 7583.Di Franco A, Cantini G, Tani A, et al. Sodium-dependent glucose transporters (SGLT) in human ischemic heart: a new potential pharmacological target. Int J Cardiol. 2017;243:86-90. DOI:10.1016/j.ijcard.2017.05.032.Di Franco A, Cantini G, Tani A, et al. Sodium-dependent glucose transporters (SGLT) in human ischemic heart: a new potential pharmacological target. Int J Cardiol. 2017;243:86-90. DOI:10.1016/j.ijcard.2017.05.032.Daniele G, Xiong J, Solis-Herrera C, et al. Dapagliflozin enhances fat oxidation and ketone production in patients with type 2 diabetes. Diabetes Care. 2016;39(11):2036-41. DOI:10.2337/dc15-2688.Daniele G, Xiong J, Solis-Herrera C, et al. Dapagliflozin enhances fat oxidation and ketone production in patients with type 2 diabetes. Diabetes Care. 2016;39(11):2036-41. DOI:10.2337/dc15-2688.Bedi KC Jr, Snyder NW, Brandimarto J, et al. Evidence for intramyocardial disruption of lipid metabolism and increased myocardial ketone utilization in advanced human heart failure. Circulation. 2016;133(8):706-16. DOI:10.1161/CIRCULATIONAHA.115.017545.Bedi KC Jr, Snyder NW, Brandimarto J, et al. Evidence for intramyocardial disruption of lipid metabolism and increased myocardial ketone utilization in advanced human heart failure. Circulation. 2016;133(8):706-16. DOI:10.1161/CIRCULATIONAHA.115.017545.Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, et al. Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics. J Am Coll Cardiol. 2019;73(15):1931-44. DOI:10.1016/j.jacc.2019.01.056.Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, et al. Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics. J Am Coll Cardiol. 2019;73(15):1931-44. DOI:10.1016/j.jacc.2019.01.056.Zhao Y, Xu L, Tian D, et al. Effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid level: a meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2018;20(2):458-62. DOI:10.1111/dom.13101.Zhao Y, Xu L, Tian D, et al. Effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid level: a meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2018;20(2):458-62. DOI:10.1111/dom.13101.Lytvyn Y, Perkins BA, Cherney DZ. Uric acid as a biomarker and a therapeutic target in diabetes. Can J Diabetes. 2015;39(3):239-46. DOI:10.1016/j.jcjd.2014.10.013.Lytvyn Y, Perkins BA, Cherney DZ. Uric acid as a biomarker and a therapeutic target in diabetes. Can J Diabetes. 2015;39(3):239-46. DOI:10.1016/j.jcjd.2014.10.013.Wheeler DC, Stefánsson BV, Jongs N, et al.; DAPA-CKD Trial Committees and Investigators. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021;9(1):22-31. DOI:10.1016/S2213-8587(20)30369-7.Wheeler DC, Stefánsson BV, Jongs N, et al.; DAPA-CKD Trial Committees and Investigators. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021;9(1):22-31. DOI:10.1016/S2213-8587(20)30369-7.Bhatt DL, Szarek M, Pitt B, et al.; SCORED Investigators. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. N Engl J Med. 2021;384(2):129-39. DOI:10.1056/NEJMoa2030186.Bhatt DL, Szarek M, Pitt B, et al.; SCORED Investigators. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. N Engl J Med. 2021;384(2):129-39. DOI:10.1056/NEJMoa2030186.Sarraju A, Li J, Cannon CP, Chang TI, et al. Effects of canagliflozin on cardiovascular, renal, and safety outcomes in participants with type 2 diabetes and chronic kidney disease according to history of heart failure: Results from the CREDENCE trial. Am Heart J. 2021;233:141-8. DOI:10.1016/j.ahj.2020.12.008.Sarraju A, Li J, Cannon CP, Chang TI, et al. Effects of canagliflozin on cardiovascular, renal, and safety outcomes in participants with type 2 diabetes and chronic kidney disease according to history of heart failure: Results from the CREDENCE trial. Am Heart J. 2021;233:141-8. DOI:10.1016/j.ahj.2020.12.008.Cherney DZI, Charbonnel B, Cosentino F, et al.; VERTIS CV Investigators. Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial. Diabetologia. 2021;64(6):1256-67. DOI:10.1007/s00125-021-05407-5.Cherney DZI, Charbonnel B, Cosentino F, et al.; VERTIS CV Investigators. Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial. Diabetologia. 2021;64(6):1256-67. DOI:10.1007/s00125-021-05407-5.Mosenzon O, Wiviott SD, Heerspink HJL, et al. The Effect of Dapagliflozin on Albuminuria in DECLARETIMI 58. Diabetes Care. 2021;44(8):1805-15. DOI:10.2337/dc21-0076.Mosenzon O, Wiviott SD, Heerspink HJL, et al. The Effect of Dapagliflozin on Albuminuria in DECLARETIMI 58. Diabetes Care. 2021;44(8):1805-15. DOI:10.2337/dc21-0076.Vallon V, Gerasimova M, Rose MA, et al. SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice. Am J Physiol Renal Physiol. 2014;306(2):F194-204. DOI:10.1152/ajprenal.00520.2013.Vallon V, Gerasimova M, Rose MA, et al. SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice. Am J Physiol Renal Physiol. 2014;306(2):F194-204. DOI:10.1152/ajprenal.00520.2013.Gilbert RE. Sodium-glucose linked transporter-2 inhibitors: potential for renoprotection beyond blood glucose lowering? Kidney Int. 2014;86(4):693-700. DOI:10.1038/ki.2013.451.Gilbert RE. Sodium-glucose linked transporter-2 inhibitors: potential for renoprotection beyond blood glucose lowering? Kidney Int. 2014;86(4):693-700. DOI:10.1038/ki.2013.451.Gallo LA, Wright EM, Vallon V. Probing SGLT2 as a therapeutic target for diabetes: basic physiology and consequences. Diab Vasc Dis Res. 2015;12(2):78-89. DOI:10.1177/1479164114561992.Gallo LA, Wright EM, Vallon V. Probing SGLT2 as a therapeutic target for diabetes: basic physiology and consequences. Diab Vasc Dis Res. 2015;12(2):78-89. DOI:10.1177/1479164114561992.Verma S, Mazer CD, Yan AT, et al. Effect of empagliflozin on left ventricular mass in patients with type 2 diabetes mellitus and coronary artery disease: the EMPA-HEART CardioLink-6 randomized clinical trial. Circulation. 2019;140(21):1693-702. DOI:10.1161/CIRCULATIONAHA.119.042375.Verma S, Mazer CD, Yan AT, et al. Effect of empagliflozin on left ventricular mass in patients with type 2 diabetes mellitus and coronary artery disease: the EMPA-HEART CardioLink-6 randomized clinical trial. Circulation. 2019;140(21):1693-702. DOI:10.1161/CIRCULATIONAHA.119.042375.Verma S, Garg A, Yan AT, et al. Effect of empagliflozin on left ventricular mass and diastolic function in individuals with diabetes: an important clue to the EMPA-REG OUTCOME trial? Diabetes Care. 2016;39(12):e212-3. DOI:10.2337/dc16-1312.Verma S, Garg A, Yan AT, et al. Effect of empagliflozin on left ventricular mass and diastolic function in individuals with diabetes: an important clue to the EMPA-REG OUTCOME trial? Diabetes Care. 2016;39(12):e212-3. DOI:10.2337/dc16-1312.Hwang IC, Cho GY, Yoon YE, et al. Different effects of SGLT2 inhibitors according to the presence and types of heart failure in type 2 diabetic patients. Cardiovasc Diabetol. 2020;19(1):69. DOI:10.1186/s12933-020-01042-3.Hwang IC, Cho GY, Yoon YE, et al. Different effects of SGLT2 inhibitors according to the presence and types of heart failure in type 2 diabetic patients. Cardiovasc Diabetol. 2020;19(1):69. DOI:10.1186/s12933-020-01042-3.Shi L, Zhu D, Wang S, et al. Dapagliflozin attenuates cardiac remodeling in mice model of cardiac pressure overload. Am J Hypertens.2019;32(5):452-9. DOI:10.1093/ajh/hpz016.Shi L, Zhu D, Wang S, et al. Dapagliflozin attenuates cardiac remodeling in mice model of cardiac pressure overload. Am J Hypertens.2019;32(5):452-9. DOI:10.1093/ajh/hpz016.Lee TM, Chang NC, Lin SZ. Dapagliflozin, a selective SGLT2 inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med. 2017;104:298-310. DOI:10.1016/j.freeradbiomed.2017.01.035.Lee TM, Chang NC, Lin SZ. Dapagliflozin, a selective SGLT2 inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med. 2017;104:298-310. DOI:10.1016/j.freeradbiomed.2017.01.035.Hsu JC, Wang CY, Su MM, et al. Effect of empagliflozin on cardiac function, adiposity, and diffuse fibrosis in patients with type 2 diabetes mellitus. Sci Rep. 2019;9(1):15348. DOI:10.1038/s41598-019-51949-5.Hsu JC, Wang CY, Su MM, et al. Effect of empagliflozin on cardiac function, adiposity, and diffuse fibrosis in patients with type 2 diabetes mellitus. Sci Rep. 2019;9(1):15348. DOI:10.1038/s41598-019-51949-5.Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, et al. Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction. J Am Coll Cardiol. 2021;26;77(3): 243-255. DOI:10.1016/j.jacc.2020.11.008.Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, et al. Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction. J Am Coll Cardiol. 2021;26;77(3): 243-255. DOI:10.1016/j.jacc.2020.11.008.Matsutani D, Sakamoto M, Kayama Y, et al. Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes. Cardiovasc Diabetol. 2018;17(1):73. DOI:10.1186/s12933-018-0717-9.Matsutani D, Sakamoto M, Kayama Y, et al. Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes. Cardiovasc Diabetol. 2018;17(1):73. DOI:10.1186/s12933-018-0717-9.Shim CY, Seo J, Cho I, et al. Randomized, controlled trial to evaluate the effect of dapagliflozin on left ventricular diastolic function in patients with type 2 diabetes mellitus: the IDDIA trial. Circulation. 2021;143(5):510-2. DOI:10.1161/CIRCULATIONAHA.120.051992.Shim CY, Seo J, Cho I, et al. Randomized, controlled trial to evaluate the effect of dapagliflozin on left ventricular diastolic function in patients with type 2 diabetes mellitus: the IDDIA trial. Circulation. 2021;143(5):510-2. DOI:10.1161/CIRCULATIONAHA.120.051992.Lee MMY, Brooksbank KJM, Wetherall K, et al. Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF). Circulation. 2021;143(6):516-25. DOI:10.1161/CIRCULATIONAHA.120.052186.Lee MMY, Brooksbank KJM, Wetherall K, et al. Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF). Circulation. 2021;143(6):516-25. DOI:10.1161/CIRCULATIONAHA.120.052186.Connelly KA, Zhang Y, Visram A, et al. Empagliflozin improves diastolic function in a nondiabetic rodent model of heart failure with preserved ejection fraction. JACC Basic Transl Sci. 2019;4(1):27-37. DOI:10.1016/j.jacbts.2018.11.010.Connelly KA, Zhang Y, Visram A, et al. Empagliflozin improves diastolic function in a nondiabetic rodent model of heart failure with preserved ejection fraction. JACC Basic Transl Sci. 2019;4(1):27-37. DOI:10.1016/j.jacbts.2018.11.010.Habibi J, Aroor AR, Sowers JR, et al. Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolicfunction in a female rodent model of diabetes. Cardiovasc Diabetol. 2017;16(1):9. DOI:10.1186/s12933-016-0489-z.Habibi J, Aroor AR, Sowers JR, et al. Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolicfunction in a female rodent model of diabetes. Cardiovasc Diabetol. 2017;16(1):9. DOI:10.1186/s12933-016-0489-z.Rau M, Thiele K, Hartmann NK, et al. Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study. Cardiovasc Diabetol. 2021;20(1):6. DOI:10.1186/s12933-020-01175-5.Rau M, Thiele K, Hartmann NK, et al. Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study. Cardiovasc Diabetol. 2021;20(1):6. DOI:10.1186/s12933-020-01175-5.Kolijn D, Pabel S, Tian Y, et al. Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Galpha oxidation. Cardiovasc Res. 2021;117(2):495-507. DOI:10.1093/cvr/cvaa123.Kolijn D, Pabel S, Tian Y, et al. Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Galpha oxidation. Cardiovasc Res. 2021;117(2):495-507. DOI:10.1093/cvr/cvaa123.Pabel S, Wagner S, Bollenberg H, et al. Empagliflozin directly improves diastolic function in human heart failure. Eur J Heart Fail. 2018;20(12):1690-700. DOI:10.1002/ejhf.1328.Pabel S, Wagner S, Bollenberg H, et al. Empagliflozin directly improves diastolic function in human heart failure. Eur J Heart Fail. 2018;20(12):1690-700. DOI:10.1002/ejhf.1328.Baartscheer A, Schumacher CA, Wust RC, et al. Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+ /H+ exchanger in rats and rabbits. Diabetologia. 2017;60(3):568-73. DOI:10.1007/s00125-016-4134-x.Baartscheer A, Schumacher CA, Wust RC, et al. Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+ /H+ exchanger in rats and rabbits. Diabetologia. 2017;60(3):568-73. DOI:10.1007/s00125-016-4134-x.Packer M, Anker SD, Butler J, et al. Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure: proposal of a novel mechanism of action. JAMA Cardiol. 2017;2:1025-9. DOI:10.1001/jamacardio.2017.2275.Packer M, Anker SD, Butler J, et al. Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure: proposal of a novel mechanism of action. JAMA Cardiol. 2017;2:1025-9. DOI:10.1001/jamacardio.2017.2275.Ye Y, Bajaj M, Yang HC, et al. SGLT-2 Inhibition with dapagliflozin reduces the activation of the Nlrp3/ASC inflammasome and attenuates the development of diabetic cardiomyopathy in mice with type 2 diabetes. Further augmentation of the effects with saxagliptin, a DPP4 inhibitor. Cardiovasc Drugs Ther. 2017;31(2):119-32. DOI:10.1007/s10557-017-6725-2.Ye Y, Bajaj M, Yang HC, et al. SGLT-2 Inhibition with dapagliflozin reduces the activation of the Nlrp3/ASC inflammasome and attenuates the development of diabetic cardiomyopathy in mice with type 2 diabetes. Further augmentation of the effects with saxagliptin, a DPP4 inhibitor. Cardiovasc Drugs Ther. 2017;31(2):119-32. DOI:10.1007/s10557-017-6725-2.Yurista SR, Sillje HHW, Oberdorf-Maass SU, et al. Sodium-glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in non-diabetic rats with left ventricular dysfunction after myocardial infarction. Eur J Heart Fail. 2019;21(7):862-73. DOI:10.1002/ejhf.1473.Yurista SR, Sillje HHW, Oberdorf-Maass SU, et al. Sodium-glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in non-diabetic rats with left ventricular dysfunction after myocardial infarction. Eur J Heart Fail. 2019;21(7):862-73. DOI:10.1002/ejhf.1473.Byrne NJ, Matsumura N, Maayah ZH, et al. Empagliflozin Blunts Worsening Cardiac Dysfunction Associated With Reduced NLRP3 (Nucleotide-Binding Domain-Like Receptor Protein 3) Inflammasome Activation in Heart Failure. Circ Heart Fail. 2020;13:e006277. DOI:10.1161/CIRCHEARTFAILURE.119.006277.Byrne NJ, Matsumura N, Maayah ZH, et al. Empagliflozin Blunts Worsening Cardiac Dysfunction Associated With Reduced NLRP3 (Nucleotide-Binding Domain-Like Receptor Protein 3) Inflammasome Activation in Heart Failure. Circ Heart Fail. 2020;13:e006277. DOI:10.1161/CIRCHEARTFAILURE.119.006277.Xu C, Wang W, Zhong J, et al. Canagliflozin exerts anti-inflammatory effects by inhibiting intracellular glucose metabolism and promoting autophagy in immune cells. Biochem Pharmacol. 2018;152:45-59. DOI:10.1016/j.bcp.2018.03.013.Xu C, Wang W, Zhong J, et al. Canagliflozin exerts anti-inflammatory effects by inhibiting intracellular glucose metabolism and promoting autophagy in immune cells. Biochem Pharmacol. 2018;152:45-59. DOI:10.1016/j.bcp.2018.03.013.Packer M. Autophagy stimulation and intracellular sodium reduction as mediators of the cardioprotective effect of sodium-glucose cotransporter 2 inhibitors. Eur J Heart Fail. 2020;22(4):618-28. DOI:10.1002/ejhf.1732.Packer M. Autophagy stimulation and intracellular sodium reduction as mediators of the cardioprotective effect of sodium-glucose cotransporter 2 inhibitors. Eur J Heart Fail. 2020;22(4):618-28. DOI:10.1002/ejhf.1732.Damman K, Beusekamp JC, Boorsma EM, et al. Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF).2020;22(4):713-22. DOI:10.1002/ejhf.1713.Damman K, Beusekamp JC, Boorsma EM, et al. Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF).2020;22(4):713-22. DOI:10.1002/ejhf.1713.Kambara T, Shibata R, Osanai H, et al. Importance of sodium-glucose cotransporter 2 inhibitor use in diabetic patients with acute heart failure. Ther Adv Cardiovasc Dis. 2019;13:1753944719894509. DOI:10.1177/1753944719894509.Kambara T, Shibata R, Osanai H, et al. Importance of sodium-glucose cotransporter 2 inhibitor use in diabetic patients with acute heart failure. Ther Adv Cardiovasc Dis. 2019;13:1753944719894509. DOI:10.1177/1753944719894509.Griffin M, Riello R, Rao VS, et al. Sodium glucose cotransporter 2 inhibitors as diuretic adjuvants in acute decompensated heart failure: a case series. ESC Heart Fail. 2020;7(4):196671. DOI:10.1002/ehf2.12759.Griffin M, Riello R, Rao VS, et al. Sodium glucose cotransporter 2 inhibitors as diuretic adjuvants in acute decompensated heart failure: a case series. ESC Heart Fail. 2020;7(4):196671. DOI:10.1002/ehf2.12759.

The authors declare that there are no conflicts of interest present.