diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM12123diaendo-12123Research ArticleОбзорыReviewИнгибиторы SGLT2 и почки: механизмы и основные эффекты у больных сахарным диабетом 2 типаSGLT2 inhibitors and kidneys: mechanisms and main effects in diabetes mellitus patientshttps://orcid.org/0000-0003-1851-0941СалуховВладимир ВладимировичSalukhovVladimir V

Доктор медицинских наук, начальник 1 кафедры  и клиники (терапии усовершенствования врачей)

eLibrary SPIN: 4531-6011

194044, г. Санкт-Петербург, ул. Академика Лебедева, д. 6

MD,PhD

eLibrary SPIN: 4531-6011

6, Academician Lebedev St., Saint-Petersburg, 194044

vlasaluk@yandex.ruhttps://orcid.org/0000-0002-7755-7275ХалимовЮрий ШавкатовичKhalimovYurii Sh.

Доктор медицинских наук, профессор, начальник кафедры  и клиники военно-полевой терапии

eLibrary SPIN: 7315-6746

194044, г. Санкт-Петербург, ул. Академика Лебедева, д. 6

MD,PhD,Professor

eLibrary SPIN: 7315-6746

6, Academician Lebedev St., Saint-Petersburg, 194044

yushkha@gmail.comhttps://orcid.org/0000-0002-9075-8274ШустовСергей БорисовичShustovSergey B.

Доктор медицинских наук, профессор, профессор  1 кафедры  и клиники (терапии усовершенствования врачей)

eLibrary SPIN: 5237-2036

194044, г. Санкт-Петербург, ул. Академика Лебедева, д. 6

MD,PhD,Professor

eLibrary SPIN: 5237-2036

6, Academician Lebedev St., Saint-Petersburg, 194044

sbs5555@mail.ruhttps://orcid.org/0000-0003-2446-2544ПоповСергей ИгоревичPopovSergey I.

Кандидат медицинских наук, преподаватель  1 кафедры  и клиники (терапии усовершенствования врачей)

eLibrary SPIN: 6428-2981

194044, г. Санкт-Петербург, ул. Академика Лебедева, д. 6

MD,PhD

eLibrary SPIN: 6428-2981

6, Academician Lebedev St., Saint-Petersburg, 194044

sergey.i.popov@gmail.comВоенно-медицинская академия им. С.М. КироваРоссияS.M. Kirov Military Medical AcademyRussian Federation202016122020235475491Copyright © Салухов В.В., Халимов Ю.Ш., Шустов С.Б., Попов С.И., 20212021Салухов В.В., Халимов Ю.Ш., Шустов С.Б., Попов С.И.Salukhov V.V., Khalimov Y.S., Shustov S.B., Popov S.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/12123

Сахарный диабет 2 типа (СД2) является причиной развития диабетической нефропатии – осложнения, определяющего высокую степень инвалидизации и смертности таких пациентов.  Существовавшие до недавнего времени подходы по нормализации уровня глюкозы не имели существенной возможности воздействия на исходы поражения почек при диабете. Ингибиторы натрий-глюкозного котранспортера 2 типа (SGLT2) представляют собой новый класс сахароснижающих препаратов, которые улучшают гликемический контроль благодаря инсулинонезависимому механизму действия, связанному с увеличением экскреции глюкозы с мочой. В обзоре представлен анализ результатов исследований, посвященных оценке одному из плейотропных действий этой группы препаратов - нефропротективному. Приведенные материалы позволяют судить о свойствах ингибиторов SGLT2 снижать риск развития и темпы прогрессирования альбуминурии, снижения скорости клубочковой фильтрации, уменьшать частоту терминальной почечной недостаточности и нуждаемости в заместительной почечной терапии у больных СД 2. В статье приводятся и анализируются существующие в настоящее время гипотезы механизма действия этих сахароснижающих препаратов. Рассматривается риск наиболее распространенных почечных осложнений при применении ингибиторов SGLT2 – урогенитальных инфекций. Указаны практические аспекты применения ингибиторов SGLT2 в современных алгоритмах оказания помощи больным СД2, а также перспективы новых рандомизированных клинических исследований

Type 2 diabetes mellitus (T2DM) is the cause of the development of diabetic nephropathy — a complication that determines the high degree of disability and mortality of such patients. Until recently, approaches to normalizing glucose levels did not have a significant possibility of influencing the outcome of kidney damage in diabetes. Type 2 sodium glucose cotransporter inhibitors (SGLT2) are a new class of glucose-lowering drugs that improve glycemic control due to an insulin-independent mechanism of action associated with increased urinary glucose excretion. The review provides an analysis of the results of studies on the assessment of nephroprotective actions — one of the pleiotropic actions of this drugs group. These materials show the properties of SGLT2 inhibitors to reduce the risk of developing and the progression of albuminuria, to save glomerular filtration rate, to reduce the frequency of end-stage renal disease and the need for renal replacement therapy in patients with T2DM. The article gives and analyzes the currently existing hypotheses of the mechanism of action of these glucose-lowering drugs. The risk of the most common renal complications with the use of SGLT2 inhibitors is considered. The practical aspects of the use of SGLT2 inhibitors in modern algorithms for the care of patients with T2DM are indicated, as well as the prospects for new randomized clinical trials. 

сахарный диабет 2 типадиабетическая нефропатияпочечная недостаточностьальбуминурияскорость клубочковой фильтрациинефропротекцияингибиторы натрий-глюкозного котранспортера 2 типаtype 2 diabetes mellitusdiabetic nephropathyend-stage renal diseasealbuminuriaglomerular filtration ratenephroprotectiontype 2 sodium glucose cotransporter inhibitorsReferencesAlicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease. Clin J Am Soc Nephrol. 2017;12(12):2032-2045. https://doi.org/10.2215/CJN.11491116Alicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease. Clin J Am Soc Nephrol. 2017;12(12):2032-2045. https://doi.org/10.2215/CJN.11491116Попов С.И., Нагибович О.А., Кицышин В.П., Шустов С.Б. Неинвазивная оценка коронарного кровотока у больных сахарным диабетом2 типа с нефропатией // Вестник Российской военно-медицинской академии. — 2010. — Т. 4. — № 32. — С. 63-67.Popov SI, Nagibovich OA, Kitsishin VP, Shustov SB. Non-invasive coronary blood flow estimation in type 2 diabetics with nephropathy. Vestnik Rossiiskoi voenno-meditsinskoi akademii. 2010; 4(32): 63-67. (in Russ.).International Diabetes Federation. IDF Diabetes Atlas, 9th Edition [Internet], 2019. Available from http://diabetesatlas.orgInternational Diabetes Federation. IDF Diabetes Atlas, 9th Edition [Internet], 2019. Available from http://diabetesatlas.orgШамхалова М.Ш., Викулова О.К., Железнякова А.В., Исаков М.А., Шестакова М.В., Дедов И.И. Эпидемиология хронической болезни почек в Российской Федерации по данным Федерального регистра взрослых пациентов с сахарным диабетом (2013-2016 гг.) // Сахарный диабет. — 2018. — Т. 21. — №3. — С. 160-169. https://doi.org/10.14341/DM9687Shamkhalova MS, Vikulova OK, Zheleznyakova AV, Isakov MA, Shestakova MV, Dedov II. Trends in the epidemiology of chronic kidney disease in Russian Federation according to the Federal Diabetes Register (2013–2016). Diabetes mellitus. 2018;21(3):160-169. (in Russ.). https://doi.org/10.14341/DM9687Швецов М.Ю., Бобкова И.Н., Колина И.Б., Камышова Е.С. Хроническая болезнь почек и нефропротективная терапия: методическое руководство для врачей. М.: НОНР, 2012. 83 с.Shvetsov MYu, Bobkova IN, Kolina IB, Kamyshova ES. Khronicheskaya bolezn’ pochek i nefroprotektivnaya terapiya: metodicheskoe rukovodstvo dlya vrachei. M.: NONR, 2012. 83 s. (in Russ.).Сергиенко И.В., Бойцов С.А., Шестакова М.В., Салухов В.В. Кардиологические аспекты сахарного диабета 2 типа. СПб.: Фолиант, 2018. 64 с.Sergienko IV, Boitsov SA, Shestakova MV, Salukhov VV. Kardiologicheskie aspekty sakharnogo diabeta 2 tipa. SPb.: Foliant, 2018. 64 s. (in Russ.).Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128. doi: https://doi.org/10.1056/NEJMoa1504720Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128. doi: https://doi.org/10.1056/NEJMoa1504720Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(7):644-657. https://doi.org/10.1056/NEJMoa1611925Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(7):644-657. https://doi.org/10.1056/NEJMoa1611925Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347-357. https://doi.org/10.1056/NEJMoa1812389Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347-357. https://doi.org/10.1056/NEJMoa1812389Ferrannini E. Sodium-Glucose Co-transporters and Their Inhibition: Clinical Physiology. Cell Metab. 2017;26(1):27-38. https://doi.org/10.1016/j.cmet.2017.04.011Ferrannini E. Sodium-Glucose Co-transporters and Their Inhibition: Clinical Physiology. Cell Metab. 2017;26(1):27-38. https://doi.org/10.1016/j.cmet.2017.04.011Beitelshees AL, Leslie BR, Taylor SI. Sodium–Glucose Cotransporter 2 Inhibitors: A Case Study in Translational Research. Diabetes. 2019;68(6):1109-1120. doi: https://doi.org/10.2337/dbi18-0006Beitelshees AL, Leslie BR, Taylor SI. Sodium–Glucose Cotransporter 2 Inhibitors: A Case Study in Translational Research. Diabetes. 2019;68(6):1109-1120. doi: https://doi.org/10.2337/dbi18-0006Alsahli M, Gerich JE. Renal glucose metabolism in normal physiological conditions and in diabetes. Diabetes Res Clin Pract. 2017;133:1-9. https://doi.org/10.1016/j.diabres.2017.07.033Alsahli M, Gerich JE. Renal glucose metabolism in normal physiological conditions and in diabetes. Diabetes Res Clin Pract. 2017;133:1-9. https://doi.org/10.1016/j.diabres.2017.07.033Cherney DZI, 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):587-597. https://doi.org/10.1161/CIRCULATIONAHA.113.005081Cherney DZI, 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):587-597. https://doi.org/10.1161/CIRCULATIONAHA.113.005081Pessoa TD, Campos LCG, Carraro-Lacroix L, et al. Functional Role of Glucose Metabolism, Osmotic Stress, and Sodium-Glucose Cotransporter Isoform-Mediated Transport on Na + /H + Exchanger Isoform 3 Activity in the Renal Proximal Tubule. J Am Soc Nephrol. 2014;25(9):2028-2039. https://doi.org/10.1681/ASN.2013060588Pessoa TD, Campos LCG, Carraro-Lacroix L, et al. Functional Role of Glucose Metabolism, Osmotic Stress, and Sodium-Glucose Cotransporter Isoform-Mediated Transport on Na + /H + Exchanger Isoform 3 Activity in the Renal Proximal Tubule. J Am Soc Nephrol. 2014;25(9):2028-2039. https://doi.org/10.1681/ASN.2013060588Kuriyama S. Protection of the kidney with sodium–glucose cotransporter 2 inhibitors: potential mechanisms raised by the largescaled randomized control trials. Clin Exp Nephrol. 2019;23(3):304-312. https://doi.org/10.1007/s10157-018-1673-0Kuriyama S. Protection of the kidney with sodium–glucose cotransporter 2 inhibitors: potential mechanisms raised by the largescaled randomized control trials. Clin Exp Nephrol. 2019;23(3):304-312. https://doi.org/10.1007/s10157-018-1673-0Alicic RZ, Neumiller JJ, Johnson EJ, et al. Sodium–Glucose Cotransporter 2 Inhibition and Diabetic Kidney Disease. Diabetes. 2019;68(2):248-257. https://doi.org/10.2337/dbi18-0007Alicic RZ, Neumiller JJ, Johnson EJ, et al. Sodium–Glucose Cotransporter 2 Inhibition and Diabetic Kidney Disease. Diabetes. 2019;68(2):248-257. https://doi.org/10.2337/dbi18-0007Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306. https://doi.org/10.1056/NEJMoa1811744Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306. https://doi.org/10.1056/NEJMoa1811744Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7(11):845-854. https://doi.org/10.1016/S2213-8587(19)30256-6Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7(11):845-854. https://doi.org/10.1016/S2213-8587(19)30256-6Шестакова М.В., Бойцов С.А., Драпкина О.М., и др. Резолюция промежуточного совещания экспертного совета по результатам исследования Empa-Reg Outcome // Рациональная фармакотерапия в кардиологии. — 2016. — Т. 12. — № 2. — С. 186-190. https://doi.org/10.20996/1819-6446-2016-12-2-186-190Shestakova MV, Boytsov SA, Drapkina OM, et al. The interim experts’ council resolution on the empa-reg outcome trial issues. Ratsional’naya farmakoterapiya v kardiologii. 2016;12(2):186-190. (in Russ.). https://doi.org/10.20996/1819-6446-2016-12-2-186-190Салухов 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. – Т. 8. – № 3. – С. 61–74. https://doi.org/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. 2019;8(3):61-74. (in Russ.). https://doi.org/10.24411/2304-9529-2019-13007Cherney DZ, Odutayo A, Aronson R, et al. Sodium Glucose Cotransporter-2 Inhibition and Cardiorenal Protection. J Am Coll Cardiol. 2019;74(20):2511-2524. https://doi.org/10.1016/j.jacc.2019.09.022Cherney DZ, Odutayo A, Aronson R, et al. Sodium Glucose Cotransporter-2 Inhibition and Cardiorenal Protection. J Am Coll Cardiol. 2019;74(20):2511-2524. https://doi.org/10.1016/j.jacc.2019.09.022Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy. N Engl J Med. 2001;345(12):861-869. https://doi.org/10.1056/NEJMoa011161Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy. N Engl J Med. 2001;345(12):861-869. https://doi.org/10.1056/NEJMoa011161Kanda E, Nangaku M. Are SGLT2 inhibitors a targeted treatment for diabetic kidney disease? Kidney Int. 2019;96(1):8-10. https://doi.org/10.1016/j.kint.2019.04.005Kanda E, Nangaku M. Are SGLT2 inhibitors a targeted treatment for diabetic kidney disease? Kidney Int. 2019;96(1):8-10. https://doi.org/10.1016/j.kint.2019.04.005Kluger AY, Tecson KM, Barbin C, et al. Cardiorenal Outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME Trials: A Systematic Review. Reviews in Cardiovascular Medicine. 2018;19(2):41-49. doi: 10.31083/j.rcm.2018.02.907Kluger AY, Tecson KM, Barbin C, et al. Cardiorenal Outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME Trials: A Systematic Review. Reviews in Cardiovascular Medicine. 2018;19(2):41-49. doi: 10.31083/j.rcm.2018.02.907Kohan DE, Fioretto P, Tang W, List JF. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. 2014;85(4):962-971. https://doi.org/10.1038/ki.2013.356Kohan DE, Fioretto P, Tang W, List JF. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. 2014;85(4):962-971. https://doi.org/10.1038/ki.2013.356Халимов Ю.Ш., Агафонов П.В., Кузьмич В.Г. Роль и место дапаглифлозина в управлении сахарным диабетом 2-го типа: от теории к практике // Медицинский совет. — 2017. — № 3. — С. 22-30. https://doi.org/10.14341/DM9687Khalimov YS, Agafonov PV, Kuzmich VG. Role and place of dapagliflozin in the management of 2nd type diabetes: from theory to practice. Meditsinskii sovet. 2017;(3):22-30. (in Russ.). https://doi.org/10.14341/DM9687Barnett AH, Mithal A, Manassie J, et al. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2014;2(5):369-384. https://doi.org/10.1016/S2213-8587(13)70208-0Barnett AH, Mithal A, Manassie J, et al. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2014;2(5):369-384. https://doi.org/10.1016/S2213-8587(13)70208-0Takashima H, Yoshida Y, Nagura C, et al. Renoprotective effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, in type 2 diabetes patients with chronic kidney disease: A randomized open-label prospective trial. Diabetes Vasc Dis Res. 2018;15(5):469-472. https://doi.org/10.1177/1479164118782872Takashima H, Yoshida Y, Nagura C, et al. Renoprotective effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, in type 2 diabetes patients with chronic kidney disease: A randomized open-label prospective trial. Diabetes Vasc Dis Res. 2018;15(5):469-472. https://doi.org/10.1177/1479164118782872Вербовой А.Ф., Пашенцева А.В., Вербовая Н.И., и др. Современные подходы к управлению факторами сердечно-сосудистого риска у больных сахарным диабетом 2-го типа // Терапевтический архив. — 2018. — T. 90. — № 8. — С. 113-117. https://doi.org/10.26442/terarkh2018908113-117Verbovoy AF, Pashentseva AV, Verbovaya NI, et al. Modern approaches to management of cardiovascular risk factors at patients with diabetes. Terapevticheskii arkhiv. 2018;90(8):113-117 (in Russ.). https://doi.org/10.26442/terarkh2018908113-117Filippatos TD, Tsimihodimos V, Liamis G, Elisaf MS. SGLT2 inhibitorsinduced electrolyte abnormalities: An analysis of the associated mechanisms. Diabetes Metab Syndr Clin Res Rev. 2018;12(1):59-63. https://doi.org/10.1016/j.dsx.2017.08.003Filippatos TD, Tsimihodimos V, Liamis G, Elisaf MS. SGLT2 inhibitorsinduced electrolyte abnormalities: An analysis of the associated mechanisms. Diabetes Metab Syndr Clin Res Rev. 2018;12(1):59-63. https://doi.org/10.1016/j.dsx.2017.08.003Корбут А.И., Климонтов В.В. Эмпаглифлозин: новая стратегия нефропротекции при сахарном диабете // Сахарный диабет. — 2017. — Т. 20. — №1. — С. 75-84. https://doi.org/10.14341/DM8005Korbut AI, Klimontov VV. Empagliflozin: a new strategy for nephroprotection in diabetes. Diabetes mellitus. 2017;20(1):75-84. (in Russ.). https://doi.org/10.14341/DM8005Cherney D, Lund SS, Perkins BA, et al. The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia. 2016;59(9):1860-1870. https://doi.org/10.1007/s00125-016-4008-2Cherney D, Lund SS, Perkins BA, et al. The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia. 2016;59(9):1860-1870. https://doi.org/10.1007/s00125-016-4008-2Dekkers CCJ, Petrykiv S, Laverman GD, et al. Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury markers. Diabetes, Obes Metab. 2018;20(8):1988-1993. https://doi.org/10.1111/dom.13301Dekkers CCJ, Petrykiv S, Laverman GD, et al. Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury markers. Diabetes, Obes Metab. 2018;20(8):1988-1993. https://doi.org/10.1111/dom.13301Салухов В.В., Халимов Ю.Ш., Шустов С.Б., Кадин Д.В. Снижение кардиоваскулярного риска у пациентов с сахарным диабетом 2 типа: обзор основных стратегий и клинических исследований // Сахарный диабет. — 2018. — Т. 21. — №3. — С. 193-205. https://doi.org/10.14341/DM9570Salukhov VV, Khalimov YuS, Shustov SB, Kadin DV. Decrease of cardiovascular risk in patients with type 2 diabetes: review of the common strategies and clinical studies. Diabetes mellitus. 2018;21(3):193-205. (in Russ.). https://doi.org/10.14341/DM9570Ferrannini E, Baldi S, Frascerra S, et al. Shift to Fatty Substrate Utilization in Response to Sodium–Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes. Diabetes. 2016;65(5):1190-1195. https://doi.org/10.2337/db15-1356Ferrannini E, Baldi S, Frascerra S, et al. Shift to Fatty Substrate Utilization in Response to Sodium–Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes. Diabetes. 2016;65(5):1190-1195. https://doi.org/10.2337/db15-1356Салухов 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. — Т. 19. — №6. — С. 494-510. https://doi.org/10.14341/DM8216Salukhov VV, Demidova TY. Empagliflozin as a new management strategy on outcomes in patients with type 2 diabetes mellitus. Diabetes mellitus. 2016;19(6):494-510 (in Russ.). https://doi.org/10.14341/DM8216Салухов В.В., Рудаков Ю.В., Шелухин В.А., и др. Обусловленная ожирением болезнь почек: современные аспекты патогенеза, диагностики и лечения (обзор литературы) // Медлайн.Ру. — 2018. — Т. 19. — №4. — С. 861-879.Salukhov VV, Rudakov YV, Shelukhin VA, et al. Obesity-related kidney disease: modern aspects of pathogenesis, diagnostics and treatment (review of the literature). Medline.ru. 2018;19(4):861-879. (in Russ.).Garvey WT, Van Gaal L, Leiter LA, et al. Effects of canagliflozin versus glimepiride on adipokines and inflammatory biomarkers in type 2 diabetes. Metabolism. 2018;85:32-37. https://doi.org/10.1016/j.metabol.2018.02.002Garvey WT, Van Gaal L, Leiter LA, et al. Effects of canagliflozin versus glimepiride on adipokines and inflammatory biomarkers in type 2 diabetes. Metabolism. 2018;85:32-37. https://doi.org/10.1016/j.metabol.2018.02.002Kumagai T, Ota T, Tamura Y, Chang WX, Shibata S, Uchida S. Time to target uric acid to retard CKD progression. Clin Exp Nephrol. 2017;21(2):182-192. https://doi.org/10.1007/s10157-016-1288-2Kumagai T, Ota T, Tamura Y, Chang WX, Shibata S, Uchida S. Time to target uric acid to retard CKD progression. Clin Exp Nephrol. 2017;21(2):182-192. https://doi.org/10.1007/s10157-016-1288-2Салухов В.В., Калинина Л.В., Кацельник Е.Ю. Гиперурикемия и ее роль в развитии некоторых сердечно-сосудистых заболеваний и сахарного диабета 2 типа // Медлайн.Ру (Medline.Ru). — 2018. — Т. 19. — №4. — С. 800-818.Salukhov VV, Kalinina LV, Katselnik EYu. Hyperuricemia and its role in the development of cardiovascular diseases and type 2 diabetes. Medline.ru. 2018;19(4):800-818. (in Russ.).Bankir L, Bouby N, Speth RC, et al. Glucagon revisited: Coordinated actions on the liver and kidney. Diabetes Res Clin Pract. 2018;146:119-129. https://doi.org/10.1016/j.diabres.2018.10.004Bankir L, Bouby N, Speth RC, et al. Glucagon revisited: Coordinated actions on the liver and kidney. Diabetes Res Clin Pract. 2018;146:119-129. https://doi.org/10.1016/j.diabres.2018.10.004Han JH, Oh TJ, Lee G, et al. The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis in ApoE −/− mice fed a western diet. Diabetologia. 2017;60(2):364-376. https://doi.org/10.1007/s00125-016-4158-2Han JH, Oh TJ, Lee G, et al. The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis in ApoE −/− mice fed a western diet. Diabetologia. 2017;60(2):364-376. https://doi.org/10.1007/s00125-016-4158-2Wilcox CS, Shen W, Boulton DW, et al. Interaction Between the Sodium‐Glucose–Linked Transporter 2 Inhibitor Dapagliflozin and the Loop Diuretic Bumetanide in Normal Human Subjects. J Am Heart Assoc. 2018;7(4). https://doi.org/10.1161/JAHA.117.007046Wilcox CS, Shen W, Boulton DW, et al. Interaction Between the Sodium‐Glucose–Linked Transporter 2 Inhibitor Dapagliflozin and the Loop Diuretic Bumetanide in Normal Human Subjects. J Am Heart Assoc. 2018;7(4). https://doi.org/10.1161/JAHA.117.007046Салухов В.В. Результаты и значение исследований EMPA-REG OUTCOME и LEADER для современной диабетологии: в поисках идеальной комбинации // Медицинский совет. — 2019. — № 4. — С. 44-51. https://doi.org/10.21518/2079-701X-2019-4-44-51Salukhov V.V. The results and the meaning of EMPA-REG OUTCOME and LEADER studies for modern diabetology: in search of ideal combination. Meditsinskiy sovet = Medical Council. 2019;(4):44-51. (in Russ.). https://doi.org/10.21518/2079-701X-2019-4-44-51Chang Y-K, Choi H, Jeong JY, et al. Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury. Long D, ed. PLoS One. 2016;11(7):e0158810. https://doi.org/10.1371/journal.pone.0158810Chang Y-K, Choi H, Jeong JY, et al. Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury. Long D, ed. PLoS One. 2016;11(7):e0158810. https://doi.org/10.1371/journal.pone.0158810Lauritsen KM, Søndergaard E, Svart M, et al. Ketone Body Infusion Increases Circulating Erythropoietin and Bone Marrow Glucose Uptake. Diabetes Care. 2018;41(12):e152-e154. https://doi.org/10.2337/dc18-1421Lauritsen KM, Søndergaard E, Svart M, et al. Ketone Body Infusion Increases Circulating Erythropoietin and Bone Marrow Glucose Uptake. Diabetes Care. 2018;41(12):e152-e154. https://doi.org/10.2337/dc18-1421Rodrigues Prestes TR, Rocha NP, Miranda AS, et al. The AntiInflammatory Potential of ACE2/Angiotensin-(1-7)/Mas Receptor Axis: Evidence from Basic and Clinical Research. Curr Drug Targets. 2017;18(11). doi: https://doi.org/10.2174/1389450117666160727142401Rodrigues Prestes TR, Rocha NP, Miranda AS, et al. The AntiInflammatory Potential of ACE2/Angiotensin-(1-7)/Mas Receptor Axis: Evidence from Basic and Clinical Research. Curr Drug Targets. 2017;18(11). doi: https://doi.org/10.2174/1389450117666160727142401Шестакова М.В. Роль тканевой ренин-ангиотензинальдостероновой системы в развитии метаболического синдрома, сахарного диабета и его сосудистых осложнений (пленарная лекция) // Сахарный диабет. — 2013. — Т. 13. — №3. — С. 14-19. https://doi.org/10.14341/2072-0351-5481Shestakova MV. The role of the tissue renin-angiotensin-aldosterone system in the development of metabolic syndrome, diabetes mellitus and itsvascular complications. Diabetes mellitus. 2010;13(3):14-19. (in Russ.). https://doi.org/10.14341/2072-0351-5481Simões e Silva A, Silveira K, Ferreira A, Teixeira M. ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis. Br J Pharmacol. 2013;169(3):477-492. doi: https://doi.org/10.1111/bph.12159Simões e Silva A, Silveira K, Ferreira A, Teixeira M. ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis. Br J Pharmacol. 2013;169(3):477-492. doi: https://doi.org/10.1111/bph.12159Cherney DZI, Cooper ME, Tikkanen I, et al. Pooled analysis of Phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin. Kidney Int. 2018;93(1):231-244. https://doi.org/10.1016/j.kint.2017.06.017Cherney DZI, Cooper ME, Tikkanen I, et al. Pooled analysis of Phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin. Kidney Int. 2018;93(1):231-244. https://doi.org/10.1016/j.kint.2017.06.017Menne J, Dumann E, Haller H, Schmidt BMW. Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis. Taal MW, ed. PLOS Med. 2019;16(12):e1002983. https://doi.org/10.1371/journal.pmed.1002983Menne J, Dumann E, Haller H, Schmidt BMW. Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis. Taal MW, ed. PLOS Med. 2019;16(12):e1002983. https://doi.org/10.1371/journal.pmed.1002983Unnikrishnan A, Kalra S, Purandare V, Vasnawala H. Genital infections with sodium glucose cotransporter-2 inhibitors: Occurrence and management in patients with type 2 diabetes mellitus. Indian J Endocrinol Metab. 2018;22(6):837. doi: https://doi.org/10.4103/ijem.IJEM_159_17Unnikrishnan A, Kalra S, Purandare V, Vasnawala H. Genital infections with sodium glucose cotransporter-2 inhibitors: Occurrence and management in patients with type 2 diabetes mellitus. Indian J Endocrinol Metab. 2018;22(6):837. doi: https://doi.org/10.4103/ijem.IJEM_159_17Figueiredo IR, Rose SCP, Freire NB, et al. Use of sodium-glucose cotransporter-2 inhibitors and urinary tract infections in type 2 diabetes patients: a systematic review. Rev Assoc Med Bras. 2019;65(2):246-252. https://doi.org/10.1590/1806-9282.65.2.246Figueiredo IR, Rose SCP, Freire NB, et al. Use of sodium-glucose cotransporter-2 inhibitors and urinary tract infections in type 2 diabetes patients: a systematic review. Rev Assoc Med Bras. 2019;65(2):246-252. https://doi.org/10.1590/1806-9282.65.2.246Rizzi M, Trevisan R. Genitourinary infections in diabetic patients in the new era of diabetes therapy with sodium-glucose cotransporter-2 inhibitors. Nutr Metab Cardiovasc Dis. 2016;26(11):963-970. https://doi.org/10.1016/j.numecd.2016.07.006Rizzi M, Trevisan R. Genitourinary infections in diabetic patients in the new era of diabetes therapy with sodium-glucose cotransporter-2 inhibitors. Nutr Metab Cardiovasc Dis. 2016;26(11):963-970. https://doi.org/10.1016/j.numecd.2016.07.006Grandy S, Fox KM, Hardy E. Prevalence and recurrence of urinary tract and genital infections among adults with and without type 2 diabetes mellitus in the general population: a longitudinal cohort study. J Diabetes Res Clin Metab. 2013;2(1):5.: https://doi.org/10.7243/2050-0866-2-5Grandy S, Fox KM, Hardy E. Prevalence and recurrence of urinary tract and genital infections among adults with and without type 2 diabetes mellitus in the general population: a longitudinal cohort study. J Diabetes Res Clin Metab. 2013;2(1):5.: https://doi.org/10.7243/2050-0866-2-5Puckrin R, Saltiel M-P, Reynier P, et al. SGLT-2 inhibitors and the risk of infections: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol. 2018;55(5):503-514. https://doi.org/10.1007/s00592-018-1116-0Puckrin R, Saltiel M-P, Reynier P, et al. SGLT-2 inhibitors and the risk of infections: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol. 2018;55(5):503-514. https://doi.org/10.1007/s00592-018-1116-0Davies MJ, D’Alessio DA, Fradkin J, et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669-2701. https://doi.org/10.2337/dci18-0033Davies MJ, D’Alessio DA, Fradkin J, et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669-2701. https://doi.org/10.2337/dci18-0033Buse JB, Wexler DJ, Tsapas A, et al. 2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2020;63(2):221-228. https://doi.org/10.1007/s00125-019-05039-wBuse JB, Wexler DJ, Tsapas A, et al. 2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2020;63(2):221-228. https://doi.org/10.1007/s00125-019-05039-wPharmacologic Approaches to Glycemic Treatment: Standarts of Medical Care in Diabetes 2020. American Diabetes Care. 2020;43 (Suppl.1):S89-S207. https://doi.org/10.2337/dc20-S009Pharmacologic Approaches to Glycemic Treatment: Standarts of Medical Care in Diabetes 2020. American Diabetes Care. 2020;43 (Suppl.1):S89-S207. https://doi.org/10.2337/dc20-S009Дедов И.И., Шестакова М.В., Майоров А.Ю., editors. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. М.: УП ПРИНТ, 2019. С. 68. [Dedov II, Shestakova MV, Maiorov AYu, editors. Algoritmy spetsializirovannoi meditsinskoi pomoshchi bol’nym sakharnym diabetom. M.: UP PRINT, 2019. S. 68. (in Russ.).Климонтов В.В., Корбут А.И. Нормоальбуминурическая хроническая болезнь почек при сахарном диабете // Терапевтический архив. — 2018. — Т. 90. — №10. — С. 94-98. https://doi.org/10.26442/terarkh201890104-98Klimontov VV, Korbut AI. Normoalbuminuric chronic kidney disease in diabetes. Terapevticheskii arkhiv. 2018;90(10):94-98. (in Russ.). https://doi.org/10.26442/terarkh201890104-98Luciano R. Transformative Research In Diabetic Nephropathy (TRIDENT ). Avaliable from: https://medicine.yale.edu/ycci/clinicaltrials/trial/5511/?tab=healthPro. (дата обращения: 16.10.2019).Luciano R. Transformative Research In Diabetic Nephropathy (TRIDENT ). Avaliable from: https://medicine.yale.edu/ycci/clinicaltrials/trial/5511/?tab=healthPro. (дата обращения: 16.10.2019).Шаронова Л.А., Вербовой А.Ф. Место глифлозинов в управлении сахарным диабетом 2 типа // Фарматека. — 2019. — Т. 26. — № 4. — С. 105-110. https://doi.org/10.18565/pharmateca.2019.4.105-110Sharonova LA, Verbovoy AF. The place of glyflozins in the management of type 2 diabetes mellitus. Pharmateca. 2019;26(4):105-110. (in Russ.). https://doi.org/10.18565/pharmateca.2019.4.105-110

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