kpcczКомплексные проблемы сердечно-сосудистых заболеванийComplex Issues of Cardiovascular Diseases2306-12782587-9537Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”10.17802/2306-1278-2021-10-3-79-89kpccz-951Research ArticleОНЛАЙН. АНАЛИТИЧЕСКИЙ ОБЗОР. Кардиология. Внутренние болезниREVIEW. Cardiology. Internal medicineКардиопротективный потенциал ингибиторов натрий-глюкозного котранспортера (фокус на эмпафлифлозин)Potential mechanisms underlying cardiovascular protection by sodium glucose cotransporter 2 inhibitors (empagliflozin)https://orcid.org/0000-0002-8387-5800СабировИ. С.SabirovI. S.

Сабиров Ибрагим Самижонович - доктор медицинских наук, профессор заведующий кафедрой терапии № 2 специальности «Лечебное дело» медицинского факультета.

Ул. Киевская, 44, Бишкек, 720000

Sabirov Ibragim S., PhD, Professor, Head of the Department of Therapy No.2, Medical Faculty.

44, Kiev St., Bishkek720000

https://orcid.org/0000-0001-8513-9279МуркамиловИ. Т.MurkamilovI. T.

Муркамилов Илхом Торобекович - кандидат медицинских наук старший преподаватель кафедры терапии № 2 специальности «Лечебное дело» медицинского факультета Кыргызско-Российский Славянский университет имени первого Президента Российской Федерации Б.Н. Ельцина; и. о. доцента кафедры факультетской терапии Кыргызская ГМА имени И.К. Ахунбаева.

Ул. Киевская, 44, Бишкек, 720000; Ул. И. Ахунбаева, 92, Бишкек, 720020

Murkamilov Ilkhom T., PhD, Senior Lecturer, Department of Therapy No.2, Medical Faculty, State Educational Institution of Higher Professional Education Kyrgyz RSU named after the First President of Russia B.N. Yeltsin; Acting Associate Professor, Department of Faculty Therapy, I.K. Akhunbaev Kyrgyz S MA.

44, Kiev St., Bishkek720000; 92, Akhunbaev St., Bishkek, 720020

murkamilov.i@mail.ruhttps://orcid.org/0000-0002-2682-4417ФоминВ. В.FominV. V.

Фомин Виктор Викторович - член-корреспондент РАН, доктор медицинских наук, профессор проректор по клинической работе и дополнительному профессиональному образованию, заведующий кафедрой факультетской терапии № 1 института клинической медицины им. Н.В. Склифосовского Первый МГМУ имени И.М. Сеченова.

Ул. Большая Пироговская, 2, Москва, 119991

Fomin Viktor V., Corresponding Member of the Russian Academy of Sciences, PhD, Professor, Vice Chancellor for Clinical and Vocational Education Programmes, Head of the Department of Faculty Therapy No.1, Institute of Clinical Medicine named after N.V. Sklifosovsky, I. M. Sechenov First Moscow SMU.

2, Bolshaya Pirogovskaya St., Moscow, 119991

Государственное образовательное учреждение высшего профессионального образования Кыргызско-Российский Славянский университет имени первого Президента Российской Федерации Б.Н. ЕльцинаКыргызстанKyrgyz Russian Slavic University named after the First President of Russia B.N. YeltsinKyrgyzstanГосударственное образовательное учреждение высшего профессионального образования Кыргызско-Российский Славянский университет имени первого Президента Российской Федерации Б.Н. Ельцина; Учреждение Кыргызская государственная медицинская академия имени И.К. АхунбаеваКыргызстанKyrgyz Russian Slavic University named after the First President of Russia B.N. Yeltsin; I.K. Akhunbaev Kyrgyz State Medical AcademyKyrgyzstanФедеральное государственное автономное образовательное учреждение высшего образования Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияFederal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of the Russian Federation (Sechenovskiy University)Russian Federation2021240920211037989Copyright © Сабиров И.С., Муркамилов И.Т., Фомин В.В., 20212021Сабиров И.С., Муркамилов И.Т., Фомин В.В.Sabirov I.S., Murkamilov I.T., Fomin V.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nii-kpssz.com/jour/article/view/951

Цель. Обзор литературы посвящен кардиопротективным возможностям представителей нового класса антигипергликемических препаратов - ингибиторов натрий-глюкозного котранспортера 2-го типа (SGLT2), которые улучшают гликемический контроль путем инсулинонезависимого механизма действия, связанного с увеличением экскреции глюкозы с мочой. В статье представлены результаты крупномасштабных клинических исследований по применению ингибиторов SGLT2 у пациентов с сахарным диабетом и без него, а также установленными сердечно-сосудистыми заболеваниями или множественными факторами сердечно-сосудистого риска. Описан ряд наиболее часто обсуждаемых кардиоспецифических механизмов, опосредованных ингибитором SGLT2, влияющим на состояние сердечно-сосудистой системы. Изложены результаты плацебо-контролируемого клинического исследования EMPA-REG OUTCOME по изучению кардиопротективных возможностей представителя ингибиторов SGLT2 - эмпаглифлозина - у пациентов с сахарным диабетом 2-го типа и сопутствующими сердечно-сосудистыми заболеваниями. В статье подчеркнута важность дальнейших исследований для установления степени вклада вышеперечисленных механизмов в кардиопротективный потенциал ингибиторов SGLT2. Поиск литературы выполнен в базе данных PubMed.

The presented literature review is devoted to the cardioprotective capabilities of a new class of antihyperglycemic drugs - sodium-glucose cotransporter 2 inhibitors (SGLT2), which improve glycemic control through an insulin-independent mechanism of action associated with an increase in urinary glucose excretion. The article presents the results of large-scale clinical trials on the use of SGLT2 inhibitors in patients with and without diabetes, and with cardiovascular diseases or multiple cardiovascular risk factors. A number of the most frequently discussed cardiac specific mechanisms mediated by the SGLT2 inhibitor affecting the Abstract           state of the cardiovascular system are presented. Moreover, the article presents the results of a placebo-controlled clinical trial entitled “Empagliflozin reduces mortality in patients with type 2 diabetes at high cardiovascular risk” (EMPA-REG oUtcOmE) to analyze the cardioprotective capabilities of SGLT2 inhibitor empagliflozin in patients with type 2 diabetes and concomitant cardiovascular diseases. The article emphasizes the importance of further research to determine the degree of contribution of the above-mentioned mechanisms to the cardioprotective potential of SGLT2 inhibitors. PubMed database was used to identify relevant studies and systematic reviews.

ингибиторы натрий-глюкозного котранспортера 2-го типафакторы ключевые слова сердечно-сосудистого рискасердечно-сосудистые заболеваниясахарный диабет 2-го типакардиопротективные механизмыsodium glucose cotransporter 2 inhibitorscardiovascular risk factorsj cardiovascular diseasestype 2 diabetes mellituscardioprotective mechanismsАвторы заявляют об отсутствии финансирования исследованияReferencesInternational Diabetes Federation. IDF Diabetes Atlas, 8th ed. Brussels, Belgium: International Diabetes Federation; 2017.International Diabetes Federation. IDF Diabetes Atlas, 8th ed. Brussels, Belgium: International Diabetes Federation; 2017.Saeedi P, Petersohn I., Salpea P., Malanda B., Karuranga S., Unwin N., Colagiuri S., Guariguata L., Motala A.A., Ogurtsova K., Shaw J.E., Bright D., Williams R.; IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. DOI: 10.1016/j.diabres.2019.107843Saeedi P, Petersohn I., Salpea P, Malanda B., Karuranga S., Unwin N., Colagiuri S., Guariguata L., Motala A.A., Ogurtsova K., Shaw J.E., Bright D., Williams R.; IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. DOI: 10.1016/j.diabres.2019.107843Standl E., Khunti K., Hansen T., Schnell O. The global epidemics of diabetes in the 21st century: Current situation and perspectives. Eur J Prev Cardiol. 2019;26(2):7-14. DOI: 10.1177/2047487319881021Standl E., Khunti K., Hansen T., Schnell O. The global epidemics of diabetes in the 21st century: Current situation and perspectives. Eur J Prev Cardiol. 2019;26(2):7-14. DOI: 10.1177/2047487319881021Sharma A., Green J., Dunning A., Lokhnygina Y., Al-Khatib S.M., Lopes R.D., Buse J.B., Lachin J.M., Van de Werf F., Armstrong P.W., Kaufman K.D., Standl E., Chan J.C.N., Distiller L. A., Scott R., Peterson E.D., Holman R.R.; TECOS Study Group. Causes of Death in a Contemporary Cohort of Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: Insights From the TECOS Trial. Diabetes Care. 2017;40(12):1763-1770. DOI: 10.2337/dc17-1091Sharma A., Green J., Dunning A., Lokhnygina Y., Al-Khatib S.M., Lopes R.D., Buse J.B., Lachin J.M., Van de Werf F., Armstrong P.W., Kaufman K.D., Standl E., Chan J.C.N., Distiller L. A., Scott R., Peterson E.D., Holman R.R.; TECOS Study Group. Causes of Death in a Contemporary Cohort of Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: Insights From the TECOS Trial. Diabetes Care. 2017;40(12):1763-1770. DOI: 10.2337/dc17-1091Mozaffarian D., Benjamin E., Go A.S., Arnett D.K., Blaha M.J., Cushman M., Das S.R., de Ferranti S., Despres J.P, Fullerton H.J., Howard VJ. et al. Executive summary: heart disease and stroke statistics—2016 update: a report from the american heart association. Circulation. 2016;133:447-54. DOI: 10.1161/CIR.0000000000000366Mozaffarian D., Benjamin E., Go A.S., Arnett D.K., Blaha M.J., Cushman M., Das S.R., de Ferranti S., Despres J.P, Fullerton H.J., Howard VJ. et al. Executive summary: heart disease and stroke statistics—2016 update: a report from the american heart association. Circulation. 2016;133:447-54. DOI: 10.1161/CIR.0000000000000366Муркамилов И.Т., Сабиров И.С., Фомин В.В., Мур-камилова Ж.А., Юсупов Ф.А., Райимжанов З.РСовремен-ные методы замедления прогрессирования хронической болезни почек при сахарном диабете II типа. Вестник современной клинической медицины. 2020;13(4):76-85. DOI:10.20969/VSKM.2020.13(4).76-85Murkamilov I.T., Sabirov I.S., Fomin V.V., Murkamilova Zh.A., Yusupov F.A., Rayimzhanov Z.R. Modern methods of slowing down the progression of chronic kidney disease in type II diabetes mellitus. The Bulletin of Contemporary Clinical Medicine. 2020; 13 (4): 7685. DOI: 10.20969/ VSKM.2020.13(4).7685.(In Russian)Салухов В.В., Демидова Т.Ю. Эмпаглифлозин как новая стратегия управления исходами у пациентов с сахарным диабетом 2 типа и высоким кардиоваскулярным риском. Сахарный диабет. 2016; 6(19): 494-510 DOI: 10.14341/DM8216Salukhov V.V., Demidova T.Yu. Empagliflozin as a new management strategy on outcomes in patients with type 2 diabetes mellitus. Diabetes mellitus. 2016;19(6):494-510. https://doi.org/10.14341/DM8216 (In Russian)Vrhovac I., Balen Eror D., Klessen D., Burger C., Breljak D., Kraus O., Radovic N., Jadrijevic S., Aleksic I., Walles T., Sauvant C., Sabolic I., Koepsell H. Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart. Pflugers Arch. 2015;467(9):1881-98. DOI: 10.1007/s00424-014-1619-7Vrhovac I., Balen Eror D., Klessen D., Burger C., Breljak D., Kraus O., Radovic N., Jadrijevic S., Aleksic I., Walles T., Sauvant C. , Sabolic I., Koepsell H. Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart. Pflugers Arch. 2015;467(9):1881-98. DOI: 10.1007/s00424-014-1619-7Ryden L., Standl E., Bartnik M., Van den Berghe G., Betteridge J. , de Boer M.J., Cosentino F., Jonsson B., Laakso M., Malmberg K. , Priori S., Ostergren J., Tuomilehto J., Thrainsdottir I. et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. 2007;28(1):88-136. DOI: 10.1093/eurheartj/ehl260Ryden L., Standl E., Bartnik M., Van den Berghe G., Betteridge J., de Boer M.J., Cosentino F., Jonsson B., Laakso M. , Malmberg K., Priori S., Ostergren J., Tuomilehto J., Thrainsdottir I. et al. Guidelines on diabetes, prediabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. 2007;28(1):88-136. DOI: 10.1093/eurheartj/ehl260Tancredi M., Rosengren A., Svensson A.M., Kosiborod M. , Pivodic A., Gudbjornsdottir S., Wedel H., Clements M., Dahlqvist S., Lind M. Excess Mortality among Persons with Type 2 Diabetes. N Engl J Med. 2015;373(18):1720-1732. DOI: 10.1056/NEJMoa1504347Tancredi M., Rosengren A., Svensson A.M., Kosiborod M., Pivodic A., Gudbjornsdottir S., Wedel H., Clements M., Dahlqvist S., Lind M. Excess Mortality among Persons with Type 2 Diabetes. N Engl J Med. 2015;373(18):1720-1732. DOI: 10.1056/NEJMoa1504347Cosentino F., Grant P. J., Aboyans V, Bailey C.J., Ceriello A., Delgado V, Federici M., Filippatos G, Grobbee D.E., Hansen T.B., Huikuri H.V., Johansson I., Juni P, Lettino M., Marx N., Mellbin L.G., Ostgren C.J., Rocca B., Roffi M., Sattar N., Seferovic P.M., Sousa-Uva M., Valensi P, Wheeler D.C.; 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/ehz486Cosentino F., Grant PJ., Aboyans V, Bailey C.J., Ceriello A., Delgado V., Federici M., Filippatos G, Grobbee D. E., Hansen T.B., Huikuri H.V., Johansson I., Juni P, Lettino M., Marx N., Mellbin L.G., Ostgren C.J., Rocca B., Roffi M., Sattar N., Seferovic P.M., Sousa-Uva M., Valensi P, Wheeler D.C.; 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/ehz486Айтбаев К.А., Муркамилов И.Т., Фомин В.В. Ингибирование HIF-пролил 4-гидроксилаз как перспективный подход к терапии кардиометаболических заболеваний. Терапевтический архив. 2018;90(8):86-94. DOI:10.26442/terarkh201890886-94Aitbaev K.A., Murkamilov I.T., Fomin V.V. nhibition of HIF-prolyl 4-hydroxylases as a promising approach to the therapy of cardiometabolic diseases. Terapevticheskii arkhiv. 2018;90(8):86-94. DOI:10.26442/terarkh201890886-94 (In Russian)Ferrannini E., Muscelli E., Frascerra S., Baldi S., Mari A., Heise T., Broedl U.C., Woerle H.J. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124(2):499-508. doi: 10.1172/JCI72227.Ferrannini E., Muscelli E., Frascerra S., Baldi S., Mari A., Heise T., Broedl U.C., Woerle H.J. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124(2):499-508. doi: 10.1172/JCI72227.Lotfy M., Adeghate J., Kalasz H., Singh J., Adeghate E. Chronic complications of diabetes mellitus: a mini review. Curr Diab Rev. 2017;13:3-10. DOI: 10.2174/1573399812666151016101622Lotfy M., Adeghate J., Kalasz H., Singh J., Adeghate E. Chronic complications of diabetes mellitus: a mini review. Curr Diab Rev. 2017;13:3-10. DOI: 10.2174/1573399812666151016101622Huynh K., Bernardo B., McMullen J., Ritchie R. Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways. Pharmacol Ther. 2014;142(3):375-415. DOI: 10.1016/j.pharmthera.2014.01.003Huynh K., Bernardo B., McMullen J., Ritchie R. Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways. Pharmacol Ther. 2014;142(3):375-415. DOI: 10.1016/j.pharmthera.2014.01.003Schilling J., Mann D. Diabetic cardiomyopathy: bench to bedside. Heart Fail Clin. 2012;8(4):619-31. DOI: 10.1016/j.hfc.2012.06.007Schilling J., Mann D. Diabetic cardiomyopathy: bench to bedside. Heart Fail Clin. 2012;8(4):619-31. DOI: 10.1016/j.hfc.2012.06.007Tate M., Grieve D.J., Ritchie R.H. Are targeted therapies for diabetic cardiomyopathy on the horizon? Clin Sci (Lond). 2017 ;131(10):897-915. DOI: 10.1042/CS20160491Tate M., Grieve D.J., Ritchie R.H. Are targeted therapies for diabetic cardiomyopathy on the horizon? Clin Sci (Lond). 2017 ;131(10):897-915. DOI: 10.1042/CS20160491Zinman B., Wanner C., Lachin J., Fitchett D., Bluhmki E., Hantel S., Mattheus M., Devins T., Johansen O.E., Woerle H.J., Broedl U.C., Inzucchi S.E.; 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/NEJMoa1504720Zinman B., Wanner C., Lachin J., Fitchett D., Bluhmki E., Hantel S., Mattheus M., Devins T., Johansen O.E., Woerle H.J., Broedl U.C., Inzucchi S.E.; 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/NEJMoa1504720Packer M., Anker S., Butler J., Filippatos G., Pocock S.J., Carson P., Januzzi J., Verma S., Tsutsui H., Brueckmann M., Jamal W., Kimura K., Schnee J., Zeller C., Cotton D. et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-1424. DOI: 10.1056/NEJMoa2022190Packer M., Anker S., Butler J., Filippatos G., Pocock S.J., Carson P, Januzzi J., Verma S., Tsutsui H., Brueckmann M., Jamal W., Kimura K., Schnee J., Zeller C., Cotton D. et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-1424. DOI: 10.1056/NEJMoa2022190Fitchett D., Inzucchi S., Cannon C., McGuire D.K., Scirica B.M., Johansen O.E., Sambevski S., Kaspers S., Pfarr E., George J.T., Zinman B. Empagliflozin Reduced Mortality and Hospitalization for Heart Failure Across the Spectrum of Cardiovascular Risk in the EMPA-REG OUTCOME Trial. Circulation. 2019;139(11):1384-1395. DOI: 10.1161/CIRCULATIONAHA.118.037778Fitchett D., Inzucchi S., Cannon C., McGuire D.K., Scirica B.M., Johansen O.E., Sambevski S., Kaspers S., Pfarr E., George J.T., Zinman B. Empagliflozin Reduced Mortality and Hospitalization for Heart Failure Across the Spectrum of Cardiovascular Risk in the EMPA-REG OUTCOME Trial. Circulation. 2019;139(11):1384-1395. DOI: 10.1161/CIRCULATIONAHA.118.037778Packer M., Butler J., Filippatos G., Jamal W, Salsali A., Schnee J., Kimura K., Zeller C., George J., Brueckmann M., Anker S.D., Zannad F.; EMPEROR-Reduced Trial Committees and Investigators.Evaluation of the effect of sodium-glucose cotransporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-Reduced trial. Eur J Heart Fail. 2019;21(10):1270-1278. DOI: 10.1002/ejhf.1536Packer M., Butler J., Filippatos G., Jamal W, Salsali A., Schnee J., Kimura K., Zeller C., George J., Brueckmann M., Anker S.D., Zannad F.; EMPEROR-Reduced Trial Committees and Investigators.Evaluation of the effect of sodium-glucose cotransporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-Reduced trial. Eur J Heart Fail. 2019;21(10):1270-1278. DOI: 10.1002/ejhf.1536Furtado R., Bonaca M., Raz I., Zelniker T.A., Mosenzon O., Cahn A., Kuder J., Murphy S.A., Bhatt D.L., Leiter L.A., McGuire D.K., Wilding J.P.H., Ruff C.T., Nicolau J.C., Gause-Nilsson I.A.M., Fredriksson M., Langkilde A.M., Sabatine M.S., Wiviott S.D. Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction. Circulation. 2019;139(22):2516-2527. DOI: 10.1161/CIRCULATIONAHA.119.039996Furtado R., Bonaca M., Raz I., Zelniker T.A., Mosenzon O., Cahn A., Kuder J., Murphy S.A., Bhatt D.L., Leiter L.A., McGuire D.K., Wilding J.P.H., Ruff C.T., Nicolau J.C., Gause-Nilsson I.A.M., Fredriksson M., Langkilde A.M., Sabatine M.S., Wiviott S.D. Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction. Circulation. 2019;139(22):2516-2527. DOI: 10.1161/CIRCULATIONAHA.119.039996Zelniker T., Wiviott S., Raz I., Im K., Goodrich E.L., Bonaca M.P., Mosenzon O., Kato E.T., Cahn A., Furtado R.H.M., Bhatt D.L., Leiter L.A., McGuire D.K., Wilding J.P.H., Sabatine M.S. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393(10166):31-39. DOI: 10.1016/S0140-6736(18)32590-XZelniker T., Wiviott S., Raz I., Im K., Goodrich E.L., Bonaca M.P, Mosenzon O., Kato E.T., Cahn A., Furtado R.H.M., Bhatt D.L., Leiter L.A., McGuire D.K., Wilding J.PH., Sabatine M.S. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393(10166):31-39. DOI: 10.1016/S0140-6736(18)32590-XWilcox C.S. Antihypertensive and Renal Mechanisms of SGLT2 (Sodium-Glucose Linked Transporter 2) Inhibitors. Hypertension. 2020;75(4):894-901. DOI:10.1161/hypertensionaha.119.11684.Wilcox C.S. Antihypertensive and Renal Mechanisms of SGLT2 (Sodium-Glucose Linked Transporter 2) Inhibitors. Hypertension. 2020;75(4):894-901. DOI:10.1161/ hypertensionaha.119.11684.Heersprink L.H.J., de Zeeuw D., Wie L., Leslie B., List J. . Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes. Metab. 2013;15(9):853-62. DOI:10.1in/dom.12127.Heersprink L.H.J., de Zeeuw D., Wie L., Leslie B., List J. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes. Metab. 2013;15(9):853-62. DOI:10.1111/dom.12127.Silva Dos Santos D., Polidoro J.Z., Borges-Junior F.A., Girardi A.C.C. Cardioprotection conferred by sodium-glucose cotransporter 2 inhibitors: a renal proximal tubule perspective. Am J Physiol Cell Physiol. 2020;318(2):328-36. DOI:10.1152/ajpcell.00275.2019.Silva Dos Santos D., Polidoro J.Z., Borges-JUnior F.A., Girardi A.C.C. Cardioprotection conferred by sodium-glucose cotransporter 2 inhibitors: a renal proximal tubule perspective. Am J Physiol Cell Physiol. 2020;318(2):328-36. DOI:10.1152/ajpcell.00275.2019.McMurray J., Solomon S., Inzucchi S., K0ber L., Kosiborod M.N., Martinez F.A., Ponikowski P., Sabatine M.S., Anand I.S., Belohlavek J. et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. DOI: 10.1056/NEJMoa1911303McMurray J., Solomon S., Inzucchi S., K0ber L., Kosiborod M.N., Martinez F.A., Ponikowski P., Sabatine M.S., Anand I.S., Belohlavek J. et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. DOI: 10.1056/NEJMoa1911303Sano M. Hemodynamic Effects of Sodium-Glucose Cotransporter 2 Inhibitors. J Clin Med Res. 2017;9(6):457-460. DOI: 10.14740/jocmr30nwSano M. Hemodynamic Effects of Sodium-Glucose Cotransporter 2 Inhibitors. J Clin Med Res. 2017;9(6):457-460. DOI: 10.14740/jocmr3011wSano M., Chen S., Imazeki H., Ochiai H., Seino Y. Changes in heart rate in patients with type 2 diabetes mellitus after treatment with luseogliflozin: Subanalysis of placebo controlled, double-blind clinical trials. J. Diabetes Investig. 2018;9 (3):638-641. DOI: 10.nn/jdi.12726Sano M., Chen S., Imazeki H., Ochiai H., Seino Y Changes in heart rate in patients with type 2 diabetes mellitus after treatment with luseogliflozin: Subanalysis of placebo controlled, double-blind clinical trials. J. Diabetes Investig. 2018;9 (3):638-641. DOI: 10.im/jdi.12726Nakayama H., Ohtsuka Y., Kawahara M. Changes in body composition during SGLT2 inhibitor treatment and their relevance to the improvement of insulin sensitivity. Diabetes Res Clin Pract. 2016;120:S50-1.Nakayama H., Ohtsuka Y., Kawahara M. Changes in body composition during SGLT2 inhibitor treatment and their relevance to the improvement of insulin sensitivity. Diabetes Res Clin Pract. 2016;120:S50-1.Iemitsu K., Iizuka T., Takihata M., Takai M., Nakajima S., Minami N., Umezawa S., Kanamori A., Takeda H., Kawata T., Ito 5., Kikuchi T., Amemiya H., Kaneshiro M., Mokubo A., Takuma T., Machimura H., Tanaka K., Asakura T., Kubota A., Aoyagi 5., Hoshino K., Ishikawa M., Obana M., Sasai N., Kaneshige H., Miyakawa M., Tanaka Y, Terauchi Y, Matsuba I. Factors influencing changes in hemoglobin A1c and body weight during treatment of type 2 diabetes with ipragliflozin: interim analysis of the ASSIGN-K study. J Clin Med Res 2016;8:373-8.DOI:10.14740/jocmr2492wIemitsu K., Iizuka T., Takihata M., Takai M., Nakajima S. , Minami N., Umezawa S., Kanamori A., Takeda H., Kawata T. , Ito S., Kikuchi T., Amemiya H., Kaneshiro M., Mokubo A., Takuma T., Machimura H., Tanaka K., Asakura T., Kubota A., Aoyagi S., Hoshino K., Ishikawa M., Obana M., Sasai N., Kaneshige H., Miyakawa M., Tanaka Y, Terauchi Y., Matsuba I. Factors influencing changes in hemoglobin A1c and body weight during treatment of type 2 diabetes with ipragliflozin: interim analysis of the ASSIGN-K study. J Clin Med Res 2016;8:373-8.DOI:10.14740/jocmr2492wPinto L., Rados D., Remonti L., Caroline Kaercher Kramer,1 Cristiane Bauermann Leitao,1 and Jorge Luiz Gross1 Efficacy of SGLT2 inhibitors in glycemic control, weight loss and blood pressure reduction: a systematic review and metaanalysis. Diabetology & metabolic syndrome, 2015;7(S1): A58 doi:10.1186/1758-5996-7-S1-A58Pinto L., Rados D., Remonti L., Caroline Kaercher Kramer,1 Cristiane Bauermann Leitao,1 and Jorge Luiz Grossl Efficacy of SGLT2 inhibitors in glycemic control, weight loss and blood pressure reduction: a systematic review and metaanalysis. Diabetology & metabolic syndrome, 2015;7(S1): A58 doi:10.1186/1758-5996-7-S1-A58Ramhez-Rodriguez A., Gonzalez-Ortiz M., Martmez-Abundis E. Effect of dapagliflozin on insulin secretion and insulin sensitivity in patients with prediabetes. Exp Clin Endocrinol Diabetes 2020;128:506-511. DOI:10.1055/a-0664-7583Ramhez-Rodriguez A., Gonzalez-Ortiz M., Martmez-Abundis E. Effect of dapagliflozin on insulin secretion and insulin sensitivity in patients with prediabetes. Exp Clin Endocrinol Diabetes 2020;128:506-511.DOI:10.1055/a-0664-7583McDowell K., Petrie M., Raihan N., Logue J. Effects of intentional weight loss in patients with obesity and heart failure: a systematic review. Obes Rev 2018;19:1189-204. DOI:10.1111/obr.12707McDowell K., Petrie M., Raihan N., Logue J. Effects of intentional weight loss in patients with obesity and heart failure: a systematic review. Obes Rev 2018;19:1189-204. DOI:10.im/obr. 12707Rajasekeran H., Lytvyn Y, Cherney D. Sodium-glucose cotransporter 2 inhibition and cardiovascular risk reduction in patients with type 2 diabetes: the emerging role of natriuresis. Kidney Int. 2016;89(3):524-6. DOI: 10.1016/j.kint.2015.12.038Rajasekeran H., Lytvyn Y, Cherney D. Sodium-glucose cotransporter 2 inhibition and cardiovascular risk reduction in patients with type 2 diabetes: the emerging role of natriuresis. Kidney Int. 2016;89(3):524-6. DOI: 10.1016/j.kint.2015.12.038Салухов В.В., Котова М.Е. Основные эффекты, вызываемые ингибиторами sglt2 у больных сахарным диабетом типа 2, и механизмы, которые их определяют. Эндокринология. Новости. Мнения. Обучение. 2019; 8(3):61-74 DOI: 10.24411/2304-9529-2019-13007Salukhov VV., Kotova M.E. Main effects caused by SGLT2 inhibitors in patients with type 2 diabetes and the mechanisms that determine them. Endokrinologiya: novosti, mneniya, obuchenie [Endocrinology: News, Opinions, Training]. 2019; 8 (3): 61-74. doi: 10.24411/2304-9529-2019-13007 (in Russian)Tikkanen I., Narko K., Zeller C., Green A., Salsali A., Broedl U.C., Woerle H.J.; EMPA-REG BP Investigators. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2015;38(3):420-8. DOI: 10.2337/dc14-1096Tikkanen I., Narko K., Zeller C., Green A., Salsali A., Broedl U.C., Woerle H.J.; EMPA-REG BP Investigators. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2015;38(3):420-8. DOI: 10.2337/dc14-1096Cherney D., Perkins B., Soleymanlou N., Har R., Fagan N., Johansen O.E., Woerle H.J., von Eynatten M., Broedl U.C. 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: 10.1186/1475-2840-13-28Cherney D., Perkins B., Soleymanlou N., Har R., Fagan N., Johansen O.E., Woerle H.J., von Eynatten M., Broedl U.C. 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: 10.1186/1475-2840-13-28Pfeifer M., Townsend R., Davies M., Vijapurkar U., Ren J. Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: a post hoc analysis. Cardiovasc Diabetol 2017;16:29. DOI:10.1186/s12933-017-0511-0Pfeifer M., Townsend R., Davies M., Vijapurkar U., Ren J. Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: a post hoc analysis. Cardiovasc Diabetol 2017;16:29. DOI:10.1186/s12933-017-0511-0Mazidi M., Rezaie P., Gao H., Kengne A. Effect of sodium-glucose cotransport-2 inhibitors on blood pressure in people with type 2 diabetes mellitus: a systematic review and meta-analysis of 43 randomized control trials with 22 528 patients. Journal of the American Heart Association, 2017;6(6):e004007. DOI:10.1161/JAHA.116.004007Mazidi M., Rezaie P., Gao H., Kengne A. Effect of sodium-glucose cotransport-2 inhibitors on blood pressure in people with type 2 diabetes mellitus: a systematic review and meta-analysis of 43 randomized control trials with 22 528 patients. Journal of the American Heart Association, 2017;6(6):e004007. DOI:10.1161/JAHA.116.004007Hamouda N.N., Sydorenko V, Qureshi M.A., Alkaabi J.M., Oz M., Howarth F.C. Dapagliflozin reduces the amplitude of shortening and Ca2+ transient in ventricular myocytes from streptozotocin-induced diabetic rats. Mol. Cell. Biochem. 2014; 400:57-68. DOI:: 10.1007/s11010-014-2262-5Hamouda N.N., Sydorenko V, Qureshi M.A., Alkaabi J.M., Oz M., Howarth F.C. Dapagliflozin reduces the amplitude of shortening and Ca2+ transient in ventricular myocytes from streptozotocin-induced diabetic rats. Mol. Cell. Biochem. 2014; 400:57-68. DOI:: 10.1007/s11010-014-2262-5Sano M. A new class of drugs for heart failure: SGLT2 inhibitors reduce sympathetic overactivity. J. Cardiol. 2018;71:471-476. DOI: 10.1016/jjjcc.2017.12.004Sano M. A new class of drugs for heart failure: SGLT2 inhibitors reduce sympathetic overactivity. J. Cardiol. 2018;71:471-476. DOI: 10.1016/jjjcc.2017.12.004Swedberg K., Young, J., Anand I., Cheng S., Desai A.S., Diaz R., Maggioni A.P., McMurray J.J., O'Connor C., Pfeffer M.A., Solomon S.D., Sun Y, Tendera M., van Veldhuisen D.J.; RED-HF Committees; RED-HF Investigators. Treatment of anemia with darbepoetin alfa in systolic heart failure. New England Journal of Medicine. 2013;368(13):1210-1219. DOI:10.1056/NEJMoa1214865Swedberg K., Young, J., Anand I., Cheng S., Desai A.S., Diaz R., Maggioni A.P., McMurray J.J., O'Connor C., Pfeffer M.A., Solomon S.D., Sun Y, Tendera M., van Veldhuisen D.J.; RED-HF Committees; RED-HF Investigators. Treatment of anemia with darbepoetin alfa in systolic heart failure. New England Journal of Medicine. 2013;368(13):1210-1219. DOI:10.1056/NEJMoa1214865Verma S., Rawat S., Ho K. Empagliflozin increases cardiac energy production in diabetes. JACC Basic Transl Sci. 2018;;3(5):575-587. DOI: 10.1016/j.jacbts.2018.07.006Verma S., Rawat S., Ho K. Empagliflozin increases cardiac energy production in diabetes. JACC Basic Transl Sci. 2018;;3(5):575-587. DOI: 10.1016/j.jacbts.2018.07.006Maiuri, M., Zalckvar, E., Kimchi, A., Kroemer G. Selfeating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007;8:741-752. DOI:10.1038/nrm2239Maiuri, M., Zalckvar, E., Kimchi, A., Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007;8:741-752. DOI:10.1038/nrm2239Ghantous C., Azrak Z., Hanache S., Abou-Kheir W., Zeidan A. Differential role of leptin and adiponectin in cardiovascular system. Int J Endocrinol. 2015:1-13.DOI:10.1155/2015/534320Ghantous C., Azrak Z., Hanache S., Abou-Kheir W., Zeidan A. Differential role of leptin and adiponectin in cardiovascular system. Int J Endocrinol. 2015:1-13. DOI:10.1155/2015/534320Iacobellis G., Ribaudo M., Zappaterreno A., Iannucci CV, Leonetti F. Relation between epicardial adipose tissue and left ventricular mass. Am J Cardiol. 2004;94:1084-7. DOI:10.1016/j.amjcard.2004.06.075Iacobellis G., Ribaudo M., Zappaterreno A., Iannucci CV, Leonetti F. Relation between epicardial adipose tissue and left ventricular mass. Am J Cardiol. 2004;94:1084-7. DOI:10.1016/j.amjcard.2004.06.075Schulze P., Kratzsch J., Linke A., Schoene N., Adams V., Gielen S., Erbs S., Moebius-Winkler S., Schuler G. Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure. Eur J Heart Fail. 2003;5:33-40. DOI:10.1016/s1388-9842(02)00177-0Schulze P., Kratzsch J., Linke A., Schoene N., Adams V., Gielen S., Erbs S., Moebius-Winkler S., Schuler G. Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure. Eur J Heart Fail. 2003;5:33-40. DOI:10.1016/s1388-9842(02)00177-0Wu P., Wen W., Li J., Xu J, Zhao M., Chen H., Sun J. Systematic review and meta-analysis of randomized controlled trials on the effect of SGLT2 inhibitor on blood leptin and adiponectin level in patients with type 2 diabetes. Horm Metab Res. 2019;51:487-94. DOI:10.1055/a-0958-2441Wu P., Wen W., Li J., Xu J, Zhao M., Chen H., Sun J. Systematic review and meta-analysis of randomized controlled trials on the effect of SGLT2 inhibitor on blood leptin and adiponectin level in patients with type 2 diabetes. Horm Metab Res. 2019;51:487-94. DOI:10.1055/a-0958-2441Барбараш О.Л., Гарганеева А.А., Гогалашвили Н.Г, Ефре-мушкина А.А., Жарский С.Л., Кашталап В.В., Кореннова О.Ю., Макаров С.А., Невзорова В.А., Протасов К.В., Устюгов С.А., Шабельникова О.Ю. Резолюция совещания экспертов Сибирского федерального округа «Эпоглифлозин и сердечная недостаточность» по результатам исследования EMPEROR-Reduced. Комплексные проблемы сердечно-сосудистых заболеваний. 2021;10(1):103-108. DOI: 10.17802/2306-1278-2021-1—1-103-108Barbarash O.L., Garganeeva A.A., Gogolashvili N.G., Efremushkina A.A., Zharskiy S.L., Kashtalap VV, Korennova O.Yu., Makarov S.A., Nevzorova V.A., Protasov K.V., Ustyugov S.A., Shabelnikova O.Yu. The resolution on empagliflozin and heart failure has been adopted by the experts of the Siberian Federal District based on the results of the EMPEROR-Reduced study. Complex Issues of Cardiovascular Diseases. 2021;10(1):103-108. (In Russian) DOI: 10.17802/2306-1278-2021-1—1-103-108

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