Cубанализы исследования DAPA-CKD: новые данные по применению ингибитора натрий-глюкозного котранспортера 2-го типа в терапии хронической болезни почек

Шамхалова М.Ш., Сухарева О.Ю., Шестакова М.В. Cубанализы исследования DAPA-CKD: новые данные по применению ингибитора натрий-глюкозного котранспортера 2-го типа в терапии хронической болезни почек. Терапевтический архив. 2022;94(10):1188–1196. DOI: 10.26442/00403660.2022.10.201883

© ООО «КОНСИЛИУМ МЕДИКУМ», 2022 г.

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Shamkhalova MS, Sukhareva OYu, Shestakova MV. Sub-analyses of the DAPA-CKD study: new data on the use of sodium-glucose cotransporter type 2 inhibitor in the treatment of chronic kidney disease. Terapevticheskii Arkhiv (Ter. Arkh.). 2022;94(10):1188–1196. DOI: 10.26442/00403660.2022.10.201883

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Аннотация

Ингибиторы натрий-глюкозного котранспортера 2-го типа прочно заняли лидирующие позиции в терапии пациентов с сахарным диабетом 2-го типа (СД 2) в связи с доказанными нефро- и кардиопротективными эффектами. Исследование DAPA-CKD (Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease), выполненное среди лиц с хронической болезнью почек различной этиологии и проведенное в смешанной популяции, включавшей и пациентов без СД 2, показало способность дапаглифлозина снижать риск первичной комбинированной конечной точки (расчетная скорость клубочковой фильтрации <15 мл/мин/1,73 м2, необходимость проведения хронического диализа или трансплантации почки, время до наступления почечной или сердечно-сосудистой смерти), а также определенных вторичных конечных точек. С учетом включения дапаглифлозина в терапевтические схемы у пациентов с хронической болезнью почек не только диабетического генеза и ожидаемого последующего значительного расширения популяции пациентов, имеющих показания к использованию препарата, большой интерес для клиницистов могут представлять результаты опубликованных запланированных субанализов исследования DAPA-CKD.

Ключевые слова: ингибитор НГЛТ-2, дапаглифлозин, исследование DAPA-CKD, хроническая болезнь почек

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Sodium-glucose cotransporter inhibitors updated their position in the therapy of patients with type 2 diabetes mellitus due to proven nephro- and cardioprotective effects. The DAPA-CKD study, performed among individuals with CKD of various etiologies, was also conducted in a mixed population, including patients without type 2 diabetes, showed the ability of dapagliflozin to reduce the risk of the primary combined endpoint (eGFR<15 ml/min/1.73 m2, the need for chronic dialysis or kidney transplantation, time to renal or cardiovascular death), and certain secondary endpoints. Due to the inclusion of dapagliflozin into the treatment of the patients with CKD of not only the diabetic origin and the expected subsequent significant expansion of the patient population with indications for the use of this drug, the review of the results of the sub-analyses of DAPA-CKD study may be of interest to the clinicians.

Keywords: SGLT-2 inhibitor, dapagliflozin, DAPA-CKD study, chronic kidney disease

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Список литературы

1. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-28. DOI:10.1056/NEJMoa1504720
2. 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
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6. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-46. DOI:10.1056/NEJMoa2024816
7. Батюшин М.М. Дапаглифлозин и профилактика неблагоприятных исходов при хронической болезни почек: результаты исследования DAPA-CKD. Терапевтический архив. 2021;93(6):713-23 [Batyushin MM. The dapagliflozin and prevention of adverse outcomes in chronic kidney disease: results of the DAPA-CKD study. Terapevticheskii Arkhiv (Ter. Arkh.). 2021;93(6):713-23 (in Russian)]. DOI:10.26442/00403660.2021.6.200891
8. Persson F, Rossing P, Vart P, et al. Efficacy and safety of dapagliflozin by baseline glycemic status: a prespecified analysis from the DAPA-CKD trial. Diabetes Care. 2021;44(8):1894-7. DOI:10.2337/dc21-0300
9. Cannon CP, Perkovic V, Agarwal R, et al. Evaluating the effects of canagliflozin on cardiovascular and renal events in patients with type 2 diabetes mellitus and chronic kidney disease according to baseline HbA1c, including those with HbA1c<7%. Circulation. 2020;141(5):407-10. DOI:10.1161/CIRCULATIONAHA.119.044359
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11. Anker SD, Butler J, Filippatos G, et al. Effect of empagliflozin on cardiovascular and renal outcomes in patients with heart failure by baseline diabetes status. Circulation. 2021;143(4):337-349. DOI:10.1161/CIRCULATIONAHA.120.051824
12. Li J, Neal B, Perkovic V, et al. Mediators of the effects of canagliflozin on kidney protection in patients with type 2 diabetes. Kidney Int. 2020;98(3):769-77. DOI:10.1016/j.kint.2020.04.051
13. Packer M. Mechanisms leading to differential hypoxia-inducible factor signaling in the diabetic kidney: modulation by SGLT2 inhibitors and hypoxia mimetics. Am J Kidney Dis. 2021;77(2):280-6. DOI:10.1053/j.ajkd.2020.04.016
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15. Wheeler DC, Stefánsson BV, Jongs N, et al. 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
16. Dekkers 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):1988-93. DOI:10.1111/dom.13301
17. Woods TC, Satou R, Miyata K, et al. Canagliflozin prevents intrarenal angiotensinogen augmentation and mitigates kidney injury and hypertension in mouse model of type 2 diabetes mellitus. Am J Nephrol. 2019;49(4):331-42. DOI:10.1159/000499597
18. Marton A, Kaneko T, Kovalik J-P, et al. Organ protection by SGLT2 inhibitors: role of metabolic energy and water conservation. Nat Rev Nephrol. 2021;17(1):65-77. DOI:10.1038/s41581-020-00350-x
19. McMurray JJV, Wheeler DC, Stefánsson BV, et al. Effects of dapagliflozin in patients with kidney disease, with and without heart failure. JACC Hear Fail. 2021;9(11):807-20. DOI:10.1016/j.jchf.2021.06.017
20. McMurray JJV, Wheeler DC, Stefánsson BV, et al. Effect of dapagliflozin on clinical outcomes in patients with chronic kidney disease, with and without cardiovascular disease. Circulation. 2021;143(5):438-48. DOI:10.1161/CIRCULATIONAHA.120.051675
21. Waijer SW, Vart P, Cherney DZI, et al. Effect of dapagliflozin on kidney and cardiovascular outcomes by baseline KDIGO risk categories: a post hoc analysis of the DAPA-CKD trial. Diabetologia. 2022;65(7):1085-97. DOI:10.1007/s00125-022-05694-6
22. de Boer IH, Caramori ML, Chan JCN, et al. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(4):S1-S115. DOI:10.1016/j.kint.2020.06.019
23. Chertow GM, Vart P, Jongs N, et al. Effects of dapagliflozin in stage 4 chronic kidney disease. J Am Soc Nephrol. 2021;32(9):2352-61. DOI:10.1681/ASN.2021020167

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1. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-28. DOI:10.1056/NEJMoa1504720
2. 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
3. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347-57. DOI:10.1056/NEJMoa1812389
4. Cannon CP, Pratley R, Dagogo-Jack S, et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med. 2020;383(15):1425-35. DOI:10.1056/NEJMoa2004967
5. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295-306. DOI:10.1056/NEJMoa1811744
6. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-46. DOI:10.1056/NEJMoa2024816
7. Batyushin MM. The dapagliflozin and prevention of adverse outcomes in chronic kidney disease: results of the DAPA-CKD study. Terapevticheskii Arkhiv (Ter. Arkh.). 2021;93(6):713-23 (in Russian). DOI:10.26442/00403660.2021.6.200891
8. Persson F, Rossing P, Vart P, et al. Efficacy and safety of dapagliflozin by baseline glycemic status: a prespecified analysis from the DAPA-CKD trial. Diabetes Care. 2021;44(8):1894-7. DOI:10.2337/dc21-0300
9. Cannon CP, Perkovic V, Agarwal R, et al. Evaluating the effects of canagliflozin on cardiovascular and renal events in patients with type 2 diabetes mellitus and chronic kidney disease according to baseline HbA1c, including those with HbA1c<7%. Circulation. 2020;141(5):407-10. DOI:10.1161/CIRCULATIONAHA.119.044359
10. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008. DOI:10.1056/NEJMoa1911303
11. Anker SD, Butler J, Filippatos G, et al. Effect of empagliflozin on cardiovascular and renal outcomes in patients with heart failure by baseline diabetes status. Circulation. 2021;143(4):337-349. DOI:10.1161/CIRCULATIONAHA.120.051824
12. Li J, Neal B, Perkovic V, et al. Mediators of the effects of canagliflozin on kidney protection in patients with type 2 diabetes. Kidney Int. 2020;98(3):769-77. DOI:10.1016/j.kint.2020.04.051
13. Packer M. Mechanisms leading to differential hypoxia-inducible factor signaling in the diabetic kidney: modulation by SGLT2 inhibitors and hypoxia mimetics. Am J Kidney Dis. 2021;77(2):280-6. DOI:10.1053/j.ajkd.2020.04.016
14. Eickhoff MK, Dekkers CCJ, Kramers BJ, et al. Effects of dapagliflozin on volume status when added to renin–angiotensin system inhibitors. J Clin Med. 2019;8(6):779-91. DOI:10.3390/jcm8060779
15. Wheeler DC, Stefánsson BV, Jongs N, et al. 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
16. Dekkers 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):1988-93. DOI:10.1111/dom.13301
17. Woods TC, Satou R, Miyata K, et al. Canagliflozin prevents intrarenal angiotensinogen augmentation and mitigates kidney injury and hypertension in mouse model of type 2 diabetes mellitus. Am J Nephrol. 2019;49(4):331-42. DOI:10.1159/000499597
18. Marton A, Kaneko T, Kovalik J-P, et al. Organ protection by SGLT2 inhibitors: role of metabolic energy and water conservation. Nat Rev Nephrol. 2021;17(1):65-77. DOI:10.1038/s41581-020-00350-x
19. McMurray JJV, Wheeler DC, Stefánsson BV, et al. Effects of dapagliflozin in patients with kidney disease, with and without heart failure. JACC Hear Fail. 2021;9(11):807-20. DOI:10.1016/j.jchf.2021.06.017
20. McMurray JJV, Wheeler DC, Stefánsson BV, et al. Effect of dapagliflozin on clinical outcomes in patients with chronic kidney disease, with and without cardiovascular disease. Circulation. 2021;143(5):438-48. DOI:10.1161/CIRCULATIONAHA.120.051675
21. Waijer SW, Vart P, Cherney DZI, et al. Effect of dapagliflozin on kidney and cardiovascular outcomes by baseline KDIGO risk categories: a post hoc analysis of the DAPA-CKD trial. Diabetologia. 2022;65(7):1085-97. DOI:10.1007/s00125-022-05694-6
22. de Boer IH, Caramori ML, Chan JCN, et al. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(4):S1-S115. DOI:10.1016/j.kint.2020.06.019
23. Chertow GM, Vart P, Jongs N, et al. Effects of dapagliflozin in stage 4 chronic kidney disease. J Am Soc Nephrol. 2021;32(9):2352-61. DOI:10.1681/ASN.2021020167

Авторы

М.Ш. Шамхалова, О.Ю. Сухарева*, М.В. Шестакова

ФГБУ «Национальный медицинский центр эндокринологии» Минздрава России, Москва, Россия
*olgasukhareva@mail.ru

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Minara S. Shamkhalova, Olga Yu. Sukhareva*, Marina V. Shestakova

National Medical Research Center for Endocrinology, Moscow, Russia
*olgasukhareva@mail.ru

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