References

medsovet

Медицинский Совет

Meditsinskiy sovet = Medical Council

2079-701X2658-5790

REMEDIUM GROUP Ltd.

10.21518/ms2025-171

medsovet-9129

Research Article

АКТУАЛЬНЫЕ ПРОБЛЕМЫ ЭНДОКРИНОЛОГИИ И КАРДИОЛОГИИ

CURRENT ISSUES IN ENDOCRINOLOGY AND CARDIOLOGY

Кардиопротективные и нефропротективные возможности ингибиторов натрий-глюкозного котранспортера 2-го типа у пациентов с сахарным диабетом 2-го типа

Cardioprotective and nephroprotective potential of sodium-glucose cotransporter type 2 inhibitors in patients with type 2 diabetes mellitus

https://orcid.org/0000-0002-9699-1210

Засыпкина

К. А.

Zasypkina

K. A.

Засыпкина Ксения Александровна, аспирант кафедры эндокринологии Института медицинского образования

197341, Россия, Санкт-Петербург, ул. Аккуратова, д. 2

Kseniia A. Zasypkina, Postgraduate Student, Department of Endocrinology of the Institute of Medical Education

2, Akkuratov St., St Petersburg, 197341, Russia

ksshteyn@mail.ru

https://orcid.org/0000-0002-0559-697X

Бабенко

А. Ю.

Babenko

A. Yu.

Бабенко Алина Юрьевна, д.м.н., профессор кафедры эндокринологии Института медицинского образования

197341, Россия, Санкт-Петербург, ул. Аккуратова, д. 2

Alina Yu. Babenko, Dr. Sci. (Med.), Professor, Department of Endocrinology of the Institute of Medical Education

2, Akkuratov St., St Petersburg, 197341, Russia

alina_babenko@mail.ru

Национальный медицинский исследовательский центр имени В.А. АлмазоваРоссияAlmazov National Medical Research CentreRussian Federation

2025

24052025

06250255

2025

Засыпкина К.А., Бабенко А.Ю.

Zasypkina K.A., Babenko A.Y.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.med-sovet.pro/jour/article/view/9129

Сахарный диабет (СД) повышает риск развития сердечно-сосудистых заболеваний (ССЗ): ишемической болезни сердца (ИБС), сердечной недостаточности (СН), фибрилляции предсердий (ФП), острых нарушений мозгового кровообращения (ОНМК), а также заболеваний аорты и периферических артерий. Помимо этого, сахарный диабет 2-го типа (СД2) является ведущей причиной хронической почечной недостаточности (ХПН). Сочетание СД2 с этими кардиоренальными сопутствующими заболеваниями повышает риск сердечно-сосудистых событий (СС-событий), смертности от ССЗ и общей смертности. В основе кардиоренального повреждения при СД2 лежит инсулинорезистеность с развитием воспаления и оксидативного стресса, что приводит к формированию интерстициального фиброза в миокарде (диабетическая кардиомиопатия), крупных сосудах и почках (диабетическая нефропатия). Отложение конечных продуктов гликозилирования, липотоксичность и нарушение микроциркуляторного русла, возникающие при СД2, а также дислипидемия и гипертония, дополнительно способствуют кардиоренальному повреждению. Наличие ССЗ и хронической болезни почек (ХБП) при СД2 и общность патофизиологических изменений при этих состояниях диктуют необходимость назначения сахароснижающих препаратов, обладающих кардио- и нефропротективными свойствами, снижающих риск неблагоприятных СС-событий и почечных рисков. В настоящей статье систематизированы и проанализированы последние исследования касательно влияния ингибиторов натрий-глюкозного котранспортера 2-го типа (ИНГЛТ-2), в частности дапаглифлозина, на течение различных ССЗ и ХБП в сочетании с СД2. Описан кардионефропротективный потенциал ИНГЛТ-2, сердечно-сосудистые и почечные преимущества при их назначении пациентам с СД2. Проанализированы исследования, подтверждающие безопасность и эффективность ИНГЛТ-2, в частности дапаглифлозина, в отношении кардио- и нефропротекции.

Diabetes mellitus (DM) increases the risk of developing cardiovascular diseases (CVD): coronary heart disease (CHD), heart failure (HF), atrial fibrillation (AF), acute cerebrovascular accidents (CVA), as well aorta and peripheral arteries diseases. In addition, type 2 diabetes mellitus (T2DM) is the leading cause of chronic kidney disease (CKD). The combination of T2DM with these cardiorenal comorbidities increases the risk of major adverse cardiovascular events (MACE) as well as mortality from CVD and allcause mortality. Cardiorenal damage in type 2 DM is based on insulin resistance, development of inflammation and oxidative stress, which leads to the formation of interstitial fibrosis in myocardium (diabetic cardiomyopathy), large vessels and kidneys (diabetic nephropathy). Advanced glycosylation end-products deposition, lipotoxicity, along with microcirculatory dysfunction associated with type 2 diabetes, as well as dyslipidemia and hypertension, further contribute to cardiorenal injury. The presence of CVD and CKD in T2DM and the commonality of pathophysiological changes in these conditions dictate the need to prescribe hypoglycemic drugs with cardioprotective and nephroprotective properties that reduce the risk of adverse cardiovascular events and renal risks. This article systematizes and analyzes the latest studies on the effect of sodium-glucose cotransporter 2 inhibitors (SGLT-2 inhibitors), in particular dapagliflozin, on the course of various CVD and CKD in combination with T2DM. The cardio-nephroprotective potential of SGLT-2 inhibitors, cardiovascular and renal benefits when this group of hypoglycemic drugs is prescribed to patients with type 2 diabetes are described. The article provides an analysis of studies confirming the safety and effectiveness of SGLT-2 inhibitors, in particular dapagliflozin, in terms of cardio- and nephroprotection.

ингибиторы натрий-глюкозного котранспортера 2-го типасахарный диабет 2-го типахроническая болезнь почекосновные неблагоприятные сердечно-сосудистые событиядапаглифлозинкардиоренальные заболевания

sodium-glucose cotransporter-2 inhibitorstype 2 diabetes mellituschronic kidney diseasemajor adverse cardiovascular eventsdapagliflozincardiorenal diseases

References1

Vijay K, Neuen BL, Lerma EV. Heart Failure in Patients with Diabetes and Chronic Kidney Disease: Challenges and Opportunities. Cardiorenal Med. 2022;12(1):1–10. https://doi.org/10.1159/000520909.

Birkeland KI, Bodegard J, Eriksson JW, Norhammar A, Haller H, Linssen GCM et al. Heart failure and chronic kidney disease manifestation and mortality risk associations in type 2 diabetes: A large multinational cohort study. Diabetes Obes Metab. 2020;22(9):1607–1618. https://doi.org/10.1111/dom.14074.

Kadowaki T, Maegawa H, Watada H, Yabe D, Node K, Murohara T, Wada J. Interconnection between cardiovascular, renal and metabolic disorders: A narrative review with a focus on Japan. Diabetes Obes Metab. 2022;24(12):2283–2296. https://doi.org/10.1111/dom.14829.

Zannad F, Rossignol P. Cardiorenal Syndrome Revisited. Circulation. 2018;138(9):929–944. https://doi.org/10.1161/CIRCULATIONAHA.117.028814.

Méndez Fernández AB, Vergara Arana A, Olivella San Emeterio A, Azancot Rivero MA, Soriano Colome T, Soler Romeo MJ. Cardiorenal syndrome and diabetes: an evil pairing. Front Cardiovasc Med. 2023;10:1185707. https://doi.org/10.3389/fcvm.2023.1185707.

Kenny HC, Abel ED. Heart Failure in Type 2 Diabetes Mellitus. Circ Res. 2019;124(1):121–141. https://doi.org/10.1161/CIRCRESAHA.118.311371.

Smith RJ, Goldfine AB, Hiatt WR. Evaluating the Cardiovascular Safety of New Medications for Type 2 Diabetes: Time to Reassess? Diabetes Care. 2016;39(5):738–742. https://doi.org/10.2337/dc15-2237.

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117–2128. https://doi.org/10.1056/NEJMoa1504720.

Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347–357. https://doi.org/10.1056/NEJMoa1812389.

McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008. https://doi.org/10.1056/NEJMoa1812389.

Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022;387(12):1089–1098. https://doi.org/10.1056/NEJMoa2206286.

McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023;44(37):3627–3639. https://doi.org/10.1093/eurheartj/ehad195.

Галявич АС, Терещенко СН, Ускач ТМ, Агеев ФТ, Аронов ДМ, Арутюнов ГП и др. Хроническая сердечная недостаточность. Клинические рекомендации 2024. Российский кардиологический журнал. 2024;29(11):6162. https://doi.org/10.15829/1560-4071-2024-6162.

Galyavich AS, Tereshchenko SN, Uskach TM, Ageev FT, Aronov DM, Arutyunov GP et al. 2024 Clinical practice guidelines for Chronic heart failure. Russian Journal of Cardiology. 2024;29(11):6162. (In Russ.) https://doi.org/10.15829/1560-4071-2024-6162.

Correction to: 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes: Developed by the task force on the management of cardiovascular disease in patients with diabetes of the European Society of Cardiology (ESC). Eur Heart J. 2024;45(7):518. https://doi.org/10.1093/eurheartj/ehad857.

Nassif ME, Windsor SL, Borlaug BA, Kitzman DW, Shah SJ, Tang F et al. The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial. Nat Med. 2021;27(11):1954–1960. https://doi.org/10.1038/s41591-021-01536-x.

Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17):e263–e421. https://doi.org/10.1016/j.jacc.2021.12.012.

Butt JH, Jhund PS, Docherty KF, Claggett BL, Vaduganathan M, Bachus E et al. Dapagliflozin and Timing of Prior Heart Failure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER. JACC Heart Fail. 2024;12(9):1586–1599. https://doi.org/10.1016/j.jchf.2024.01.018.

Morillas H, Galcerá E, Alania E, Seller J, Larumbe A, Núñez J, Valle A. Sodium-glucose Co-transporter 2 Inhibitors in Acute Heart Failure: A Review of the Available Evidence and Practical Guidance on Clinical Use. Rev Cardiovasc Med. 2022;23(4):139. https://doi.org/10.31083/j.rcm2304139.

Cox ZL, Collins SP, Hernandez GA, McRae AT 3rd, Davidson BT, Adams K et al. Efficacy and Safety of Dapagliflozin in Patients With Acute Heart Failure. J Am Coll Cardiol. 2024;83(14):1295–1306. https://doi.org/10.1016/j.jacc.2024.02.009.

James S, Erlinge D, Storey RF, McGuire DK, de Belder M, Eriksson N et al. Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure. NEJM Evid. 2024;3(2):EVIDoa2300286. https://doi.org/10.1056/EVIDoa2300286.

Movahed MR, Hashemzadeh M, Jamal MM. Diabetes mellitus is a strong, independent risk for atrial fibrillation and flutter in addition to other cardiovascular disease. Int J Cardiol. 2005;105(3):315–318. https://doi.org/10.1016/j.ijcard.2005.02.050.

Aune D, Feng T, Schlesinger S, Janszky I, Norat T, Riboli E. Diabetes mellitus, blood glucose and the risk of atrial fibrillation: A systematic review and meta-analysis of cohort studies. J Diabetes Complications. 2018;32(5):501–511. https://doi.org/10.1016/j.jdiacomp.2018.02.004.

Van Deutekom C, Van Gelder IC, Rienstra M. Atrial fibrillation and heart failure temporality: does it matter? Europace. 2023;25(2):247–248. https://doi.org/10.1093/europace/euac255.

Scheen AJ. Antidiabetic agents and risk of atrial fibrillation/flutter: A comparative critical analysis with a focus on differences between SGLT2 inhibitors and GLP-1 receptor agonists. Diabetes Metab. 2022;48(6):101390. https://doi.org/10.1016/j.diabet.2022.101390.

Butt JH, Docherty KF, Jhund PS, de Boer RA, Böhm M, Desai AS et al. Dapagliflozin and atrial fibrillation in heart failure with reduced ejection fraction: insights from DAPA-HF. Eur J Heart Fail. 2022;24(3):513–525. https://doi.org/10.1002/ejhf.2381.

Zelniker TA, Bonaca MP, Furtado RHM, Mosenzon O, Kuder JF, Murphy SA et al. Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus: Insights From the DECLARE-TIMI 58 Trial. Circulation. 2020;141(15):1227–1234. https://doi.org/10.1161/CIRCULATIONAHA.119.044183.

Scheen AJ. Glucose-lowering agents and risk of ventricular arrhythmias and sudden cardiac death: A comprehensive review ranging from sulphonylureas to SGLT2 inhibitors. Diabetes Metab. 2022;48(6):101405. https://doi.org/10.1016/j.diabet.2022.101405.

Curtain JP, Docherty KF, Jhund PS, Petrie MC, Inzucchi SE, Køber L et al. Effect of dapagliflozin on ventricular arrhythmias, resuscitated cardiac arrest, or sudden death in DAPA-HF. Eur Heart J. 2021;42(36):3727–3738. https://doi.org/10.1093/eurheartj/ehab560.

Ilyas F, Jones L, Tee SL, Horsfall M, Swan A, Wollaston F et al. Acute pleiotropic effects of dapagliflozin in type 2 diabetic patients with heart failure with reduced ejection fraction: a crossover trial. ESC Heart Fail. 2021;8(5):4346–4352. https://doi.org/10.1002/ehf2.13553.

Дедов ИИ, Шестакова МВ, Майоров АЮ, Мокрышева НГ, Андреева ЕН, Безлепкина ОБ и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. 11-й выпуск. Сахарный диабет. 2023;26(2S):1–157. https://doi.org/10.14341/DM13042.

Dedov I, Shestakova M, Mayorov A, Mokrysheva N, Andreeva E, Bezlepkina O et al. Standards of Specialized Diabetes Care. 11th Edition. Diabetes Mellitus. 2023;26(2S):1–157. (In Russ.) https://doi.org/10.14341/DM13042.

He G, Yang G, Huang X, Luo D, Tang C, Zhang Z. SGLT2 inhibitors for prevention of primary and secondary cardiovascular outcomes: A meta-analysis of randomized controlled trials. Heart Lung. 2023;59:109–116. https://doi.org/10.1016/j.hrtlng.2023.02.009.

Thangjui, S, Ahmady, A, Kiani, R, Trongtorsak A, Bathini T, Shrestha B. The impact of sglt2 inhibitor on patient with myocardial infarction: systematic review and meta-analysis. JACC. 2023;81(8_S):1329. Available at: https://www.jacc.org/doi/abs/10.1016/S0735-1097(23)01773-4.

Furtado RHM, Bonaca MP, Raz I, Zelniker TA, Mosenzon O, Cahn A et al. Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2

Diabetes Mellitus and Previous Myocardial Infarction. Circulation. 2019;139(22):2516–2527. https://doi.org/10.1161/CIRCULATIONAHA.119.039996.

Li C, Zhang J, Xue M, Li X, Han F, Liu X et al. SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart. Cardiovasc Diabetol. 2019;18(1):15. https://doi.org/10.1186/s12933-019-0816-2.

Kwon O, Myong JP, Lee Y, Choi YJ, Yi JE, Seo SM et al. Sodium-Glucose Cotransporter-2 Inhibitors After Acute Myocardial Infarction in Patients With Type 2 Diabetes: A Population-Based Investigation. J Am Heart Assoc. 2023;12(14):e027824. https://doi.org/10.1161/JAHA.122.027824.

Dayem KA, Younis O, Zarif B, Attia S, AbdelSalam A. Impact of dapagliflozin on cardiac function following anterior myocardial infarction in nondiabetic patients – DACAMI (a randomized controlled clinical trial). Int J Cardiol. 2023;379:9–14. https://doi.org/10.1016/j.ijcard.2023.03.002.

Oshima H, Miki T, Kuno A, Mizuno M, Sato T, Tanno M et al. Empagliflozin, an SGLT2 Inhibitor, Reduced the Mortality Rate after Acute Myocardial Infarction with Modification of Cardiac Metabolomes and Antioxidants in Diabetic Rats. J Pharmacol Exp Ther. 2019;368(3):524–534. https://doi.org/10.1124/jpet.118.253666.

Peng Y, Guo M, Luo M, Lv D, Liao K, Luo S, Zhang B. Dapagliflozin ameliorates myocardial infarction injury through AMPKα-dependent regulation of oxidative stress and apoptosis. Heliyon. 2024;10(7):e29160. https://doi.org/10.1016/j.heliyon.2024.e29160.

García-Carro C, Vergara A, Bermejo S, Azancot MA, Sánchez-Fructuoso AI, de la Nieta MDS et al. How to assess diabetic kidney disease progression? From albuminuria to GFR. J Clin Med. 2021;10(11):2505. https://doi.org/10.3390/jcm10112505.

Mosenzon O, Wiviott SD, Cahn A, Rozenberg A, Yanuv I, Goodrich EL et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARETIMI 58 randomised trial. Lancet Diabetes Endocrinol. 2019;7(8):606–617. https://doi.org/10.1016/S2213-8587(19)30180-9.

Lazzaroni E, Lunati ME, Montefusco L, Pastore I, Chebat E, Cimino V et al. Dapagliflozin acutely improves kidney function in type 2 diabetes mellitus. The PRECARE study. Pharmacol Res. 2022;183:106374. https://doi.org/10.1016/j.phrs.2022.106374.

Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou F-F et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–1446. https://doi.org/10.1056/NEJMoa2024816.

American Diabetes Association Professional Practice Committee. 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47(S1):S219–S230. https://doi.org/10.2337/dc24-S011.

Bakris GL. Major Advancements in Slowing Diabetic Kidney Disease Progression: Focus on SGLT2 Inhibitors. Am J Kidney Dis. 2019;74(5):573–575. https://doi.org/10.1053/j.ajkd.2019.05.009.

Paolisso P, Bergamaschi L, Cesaro A, Gallinoro E, Gragnano F, Sardu C et al. Impact of SGLT2-inhibitors on contrast-induced acute kidney injury in diabetic patients with acute myocardial infarction with and without chronic kidney disease: Insight from SGLT2-I AMI PROTECT registry. Diabetes Res Clin Pract. 2023;202:110766. https://doi.org/10.1016/j.diabres.2023.110766

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