Место ингибиторов натрий-глюкозного ко-транспортера 2 в лечении сахарного диабета 2 типа и его осложнений с позиции доказательной медицины


DOI: https://dx.doi.org/10.18565/therapy.2020.8.90-104

Т.Ю. Демидова, Я.Г. Алексеева

1) ФГАОУ ВО «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Минздрава России, г. Москва; 2) АО «Астеллас Фарма», г. Москва
Эффективное лечение сахарного диабета (СД) 2 типа с фокусом на профилактику сердечно-сосудистых заболеваний (ССЗ) становится все более актуальной проблемой общественного здравоохранения, требующей многофакторного регулирования всех факторов кардиоваскулярного риска, а не только достижения гликемического контроля. Ингибиторы натрий-глюкозного ко-транспортера 2 (иНГЛТ-2) — инновационный класс сахароснижающих препаратов с универсальным, выраженным и устойчивым во времени гипогликемическим действием, а также многочисленными негликемическими эффектами. Применение иНГЛТ-2 открывает большие перспективы не только в плане улучшения гликемического контроля, но и в профилактике микро- и макрососудистых осложнений СД 2 типа. В настоящей статье представлены основные преимущества данной группы лекарственных средств при лечении СД 2 типа, а также рассмотрены стратегии, которые могут снизить риск развития ССЗ в этой популяции.
Ключевые слова: ингибиторы натрий-глюкозного ко-транспортера 2, сахарный диабет 2 типа, сердечно-сосудистый риск
Полный текст статьи доступен
в "Библиотеке Врача"

Литература


  1. IDF Diabetes Atlas. 2017. 8th Edition. Available from: http://www.diabetesatlas.org/component/attachments/?task=download&id=254 (date of access – 01.12.2020].

  2. Дедов И.И., Шестакова М.В., Викулова О.К. с соавт. Сахарный диабет в Российской Федерации: распространенность, заболеваемость, смертность, параметры углеводного обмена и структура сахароснижающей терапии по данным федерального регистра сахарного диабета, статус 2017 г. Сахарный диабет. 2018; 3: 144–159.

  3. Calderon-Larranaga A., Abad-Dieza G.M., Gimeno-Feliuet L.A. et al. Global health care use by patients with type-2 diabetes: Does the type of comorbidity matter? Eur J Intern Med. 2015; 26(3): 203–10. doi: 10.1016/j.ejim.2015.02.011.

  4. Nowakowska M., Zghebi S.S., Ashcroft D.M. et al. The comorbidity burden of type 2 diabetes mellitus: patterns, clusters and predictions from a large English primary care cohort. BMC Med. 2019; 17(1): 145. doi: 10.1186/s12916-019-1373-y.

  5. Gaede P., Oellgaard J., Carstensen B. et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia. 2016; 59(11): 2298–2307. doi: 10.1007/s00125-016-4065-6.

  6. Дедов И.И., Шестакова М.В., Майоров А.Ю. с соавт. Алгоритмы специализированной медицинской помощи больным сахарным диабетом / под ред. И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. 9-й выпуск. Сахарный диабет. 2019; S1–1: 1–144.

  7. American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020; 43(Suppl 1): S98–S110. doi: 10.2337/dc20-S009.

  8. Wan E.Y.F., Fung C.S.C., Jiao F.F. et al. Five-Year effectiveness of the multidisciplinary Risk Assessment and Management Programme-Diabetes Mellitus (RAMP-DM) on diabetes-related complications and health service uses-a population-based and propensity-matched cohort study. Diabetes Care. 2018; 41(1): 49–59. doi: 10.2337/dc17-0426.

  9. Lim S., Eckel R.H., Koh K.K. Clinical implications of current cardiovascular outcome trials with sodium glucose cotransporter-2 (SGLT2) inhibitors. Atherosclerosis. 2018; 272: 33–40. doi: 10.1016/j.atherosclerosis.2018.03.013.

  10. Cosentino F., Grant P.J., Aboyans V. et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020; 41(2): 255–323. doi: 10.1093/eurheartj/ehz486.

  11. Kosiborod M., Cavender M.A., Fu A.Z. et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: The CVD-REAL study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors). Circulation. 2017; 136(3): 249–59. doi: 10.1161/CIRCULATIONAHA.117.029190.

  12. Kosiborod M., Lam C.S.P., Kohsaka S. et al. Cardiovascular events associated with SGLT-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL 2 study. J Am Coll Cardiol. 2018; 71(23): 2628–39. doi: 10.1016/j.jacc.2018.03.009.

  13. Birkeland K.I., Bodegard J., Banerjee A. et al. Lower cardiorenal risk with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes without cardiovascular and renal diseases: A large multinational observational study. Diabetes Obes Metab. 2021; 23(1): 75–85. doi: 10.1111/dom.14189.

  14. Handelsman Y. Rationale for the early use of sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes. Adv Ther. 2019; 36(10): 2567–86. doi: 10.1007/s12325-019-01054-w.

  15. Deerochanawong C., Chan S.P., Matawaran B.J. et al. Use of sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors: An Asian perspective and expert recommendations. Diabetes Obes Metab. 2019; 21(11): 2354–67. doi: 10.1111/dom.13819.

  16. Fonseca V.A., Ferrannini E., Wilding J.P. et al. Active- and placebo-controlled dose-finding study to assess the efficacy, safety, and tolerability of multiple doses of ipragliflozin in patients with type 2 diabetes mellitus. J Diabetes Complications. 2013; 27(3): 268–73. doi: 10.1016/j.jdiacomp.2012.11.005.

  17. Kashiwagi A., Kazuta K., Takinami Y. et al. Ipragliflozin improves glycemic control in Japanese patients with type 2 diabetes mellitus: the BRIGHTEN study. Diabetol Int. 2015; 6(1): 8–18.

  18. Elgebaly A., Abdelazeim N., Abdelazeim B. et al. Tolerability and efficacy of ipragliflozin in the management of inadequately controlled type 2 diabetes mellitus: a systematic review and meta-analysis. Exp Clin Endocrinol Diabetes. 2018 Jun 18. doi: 10.1055/a-0579-7860.

  19. Kashiwagi A., Kazuta K., Goto K. et al. Ipragliflozin in combination with metformin for the treatment of Japanese patients with type 2 diabetes: ILLUMINATE, a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab. 2015; 17(3): 304–08. doi: 10.1111/dom.12331.

  20. Kashiwagi A., Akiyama N., Shiga T. et al. Efficacy and safety of ipragliflozin as an add-on to a sulfonylurea in Japanese patients with inadequately controlled type 2 diabetes: results of the randomized, placebo-controlled, double-blind, phase III EMIT study. Diabetol Int. 2015; 6(2): 125–38.

  21. Kashiwagi A., Shiga T., Akiyamaet N. et al. Efficacy and safety of ipragliflozin as an add-on to pioglitazone in Japanese patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study (the SPOTLIGHT study). Diabetol Int. 2015; 6(2): 104–116.

  22. Kashiwagi A., Isaka H., Kawano H. Long-term safety, tolerability and efficacy of ipragliflozin in combination with a dipeptidyl peptidase-4 inhibitor in Japanese patients with type 2 diabetes mellitus inadequately controlled with a dipeptidyl peptidase-4 inhibitor alone – DAYLIGHT Study. Jpn Pharmacol Ther. 2014; 42(12): 941–57.

  23. Lu C.H., Min K.W., Chuang L.M. et al. Efficacy, safety, and tolerability of ipragliflozin in Asian patients with type 2 diabetes mellitus and inadequate glycemic control with metformin: Results of a phase 3 randomized, placebo-controlled, double-blind, multicenter trial. J Diabetes Investig. 2016; 7(3): 366–73. doi: 10.1111/jdi.12422.

  24. Han K.-A., Chon S., Chung C.H. et al. Efficacy and safety of ipragliflozin as an add-on therapy to sitagliptin and metformin in korean patients with inadequately controlled type 2 diabetes mellitus: A randomized controlled trial. Diabetes Obes Metab. 2018; 20(10): 2408–15. doi: 10.1111/dom.13394.

  25. Ishihara H., Yamaguchi S., Nakao I. et al. Efficacy and safety of ipragliflozin as add-on therapy to insulin in Japanese patients with type 2 diabetes mellitus (IOLITE): a multi-centre, randomized, placebo-controlled, double-blind study. Diabetes Obes Metab. 2016; 18(12): 1207–16. doi: 10.1111/dom.12745.

  26. Ishihara Н., Yamaguchi S., Nakao I., Sakatani T. Ipragliflozin add-on therapy to a GLP-1 receptor agonist in Japanese patients with type 2 diabetes (AGATE): A 52-week open-label study. Diabetes Ther. 2018; 9(4): 1549–67. doi: 10.1007/s13300-018-0455-8.

  27. Shestakova M.V., Wilding J.P.H., Wilpshaar W. et al. A phase 3 randomized placebo-controlled trial to assess the efficacy and safety of ipragliflozin as an add-on therapy to metformin in Russian patients with inadequately controlled type 2 diabetes mellitus. Diabetes Res Clin Pract. 2018; 146: 240–50. doi: 10.1016/j.diabres.2018.10.018.

  28. Дедов И.И., Мельниченко Г.А., Шестакова М.В. с соавт. Национальные клинические рекомендации по лечению морбидного ожирения у взрослых. 3-й пересмотр (Лечение морбидного ожирения у взрослых). Ожирение и метаболизм. 2018; 1: 53–70.

  29. Hsia D.S., Grove O., Cefalu W.T. An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus. Curr Opin Endocrinol Diabetes Obes. 2017; 24(1): 73–79. doi: 10.1097/MED.0000000000000311.

  30. Nakamura I., Maegawa H., Tobe, K. et al. Safety and efficacy of ipragliflozin in Japanese patients with type 2 diabetes in realworld clinical practice: interim results of the STELLA-LONG TERM post-marketing surveillance study. Expert Opin Pharmacother. 2018; 19(3): 189–201. doi: 10.1080/14656566.2017.1408792.

  31. Kawata T., Iizuka T., Iemitsu K. et al. Ipragliflozin improves glycemic control and decreases body fat in patients with type 2 diabetes mellitus. J Clin Med Res. 2017; 9(7): 586–95. doi: 10.14740/jocmr3038w.

  32. Koshizaka M., Ishikawa K., Ishibashi R. et al. Comparing the effects of ipragliflozin versus metformin on visceral fat reduction and metabolic dysfunction in Japanese patients with type 2 diabetes treated with sitagliptin: A prospective, multicentre, open-label, blinded-endpoint, randomized controlled study (PRIME-V study). Diabetes Obes Metab. 2019; 21(8): 1990–95. doi:10.1111/dom.13750.

  33. Reed J.W. Impact of sodium-glucose cotransporter 2 inhibitors on blood pressure. Vasc Health Risk Manag. 2016; 12: 393–405. doi: 10.2147/VHRM.S111991.

  34. Kawasoe S., Maruguchi Y., Kajiya S. et al. Mechanism of the blood pressure-lowering effect of sodium-glucose cotransporter 2 inhibitors in obese patients with type 2 diabetes. BMC Pharmacol Toxicol. 2017; 18(1): 23. doi: 10.1186/s40360-017-0125-x.

  35. Filippatos T.D., Tsimihodimos V., Elisaf M.S. Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors. Expert Opin Pharmacother. 2016; 17(12): 1581–83. doi: 10.1080/14656566.2016.1201073.

  36. Kashiwagi A., Yoshida S., Kawamuki K. et al. Effects of ipragliflozin, a selective sodium–glucose co-transporter 2 inhibitor, on blood pressure in Japanese patients with type 2 diabetes mellitus: a pooled analysis of six randomized, a placebo-controlled clinical trials. Diabetol Int. 2017; 8(1): 76–86. doi: 10.1007/s13340-016-0283-x.

  37. Farmer J.A. Diabetic dyslipidemia and atherosclerosis: evidence from clinical trials. Curr Diab Rep. 2008; 8(1): 71–77. doi: 10.1007/s11892-008-0013-2.

  38. Кухарчук В.В., Ежов М.В., Сергиенко И.В. с соавт. Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации, VII пересмотр. Атеросклероз и дислипидемии. 2020; 1: 7–40.

  39. Inzucchi S.E., Zinman B., Wanner C. et al. SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res. 2015; 12(2): 90–100. doi: 10.1177/1479164114559852.

  40. Kashiwagi A., Sakatani T., Nakamura I. et al. Improved cardiometabolic risk factors in Japanese patients with type 2 diabetes treated with ipragliflozin: a pooled analysis of six randomized, placebo-controlled trials. Endocr J. 2018; 65(7): 693–705. doi: 10.1507/endocrj.EJ17-0491.

  41. Bando Y., Tohyama H., Aoki K., et al. Ipragliflozin lowers small, dense low-density lipoprotein cholesterol levels in Japanese patients with type 2 diabetes mellitus. J Clin Transl Endocrinol. 2016; 6: 1–7. doi:10.1016/j.jcte.2016.06.001.

  42. Lo K.В., Gul F., Ram P. et al. The effects of SGLT2 inhibitors on cardiovascular and renal outcomes in diabetic patients: A systematic review and meta-analysis. Cardiorenal Med. 2020; 10(1): 1–10. doi: 10.1159/000503919.

  43. Zelniker T.A., Wiviott S.D., Raz I. et al. 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-X.

  44. 44. McGuire D.K., Shih W.J., Cosentino F. et al. Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: A meta-analysis. JAMA Cardiol. 2020; e204511. doi: 10.1001/jamacardio.2020.4511.

  45. Arnett D.K., Blumenthal R.S., Albert M.A. et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation. 2019; 140(11): e596–e646. doi: 10.1161/CIR.0000000000000678.

  46. Radholm K., Wu J.H., Wong M.G. et al. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular disease, death and safety outcomes in type 2 diabetes – A systematic review. Diabetes Res Clin Pract. 2018; 140: 118–28. doi: 10.1016/j.diabres.2018.03.027.

  47. Abdelgadir E., Rashid F., Bashier A., Ali R. SGLT-2 inhibitors and cardiovascular protection: lessons and gaps in understanding the current outcome trials and possible benefits of combining SGLT-2 inhibitors with GLP-1 agonists. J Clin Med Res. 2018; 10(8): 615–25. doi: 10.14740/jocmr3467w.

  48. Dekkers C.C.J., Gansevoort R.T. Sodium-glucose cotransporter 2 inhibitors: extending the indication to non-diabetic kidney disease? Nephrol Dial Transplant. 2020; 35: i33–i42. doi: 10.1093/ndt/gfz264.

  49. Heerspink H.J.L., Kosiborod M., Inzucchi S.E., Cherney D.Z.I. Renoprotective effects of sodium-glucose cotransporter-2 inhibitors. Kidney International. 2018; 94; 26–39. doi: 10.1016/j.kint.2017.12.027.

  50. Matsuba I., Kawata T., Iemitsu K. et al. Effects of ipragliflozin on the development and progression of kidney disease in patients with type 2 diabetes: An analysis from a multicenter prospective intervention study. J Diabetes Investig. J Diabetes Investig. 2020; 11(5): 1248–57. doi: 10.1111/jdi.13248.

  51. Horii T., Oikawa Y., Kunisada N. et al. Real-world risk of hypoglycemia-related hospitalization in Japanese patients with type 2 diabetes using SGLT2 inhibitors: a nationwide cohort study. BMJ Open Diabetes Research and Care. 2020; 8: e001856. doi: 10.1136/bmjdrc-2020-001856.

  52. Ueda P., Svanstrom H., Melbye M. et al. Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study. BMJ. 2018; 363: k4365. doi: 10.1136/bmj.k4365.

  53. Donnan J.R., Grandy C.A., Chibrikov E. et al. Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis. BMJ Open. 2019; 9(1): e022577. doi: 10.1136/bmjopen-2018-022577.

  54. Puckrin 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): 503–14. doi: 10.1007/s00592-018-1116-0.

  55. Fadini G.P., Avogaro A. SGLT2 inhibitors and amputations in the US FDA Adverse Event Reporting System

  56. Ryan P.B., Buse J.B., Schuemie M.J. et al. Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real-world meta-analysis of 4 observational databases (OBSERVE-4D). Diabetes Obes. Metab. 2018; 20: 2585–97. doi: 10.1111/dom.13424.


Об авторах / Для корреспонденции

Татьяна Юльевна Демидова, д.м.н., профессор, зав. кафедрой эндокринологии лечебного факультета ФГАОУ ВО «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Минздрава России. Адрес: 109263, г. Москва, ул. Шкулева, д. 4, к. 1. E-mail: t.y.demidova@gmail.com. ORCID: 0000-0001-6385-540X
Яна Геннадиевна Алексеева, к.м.н., старший медицинский менеджер компании АО «Астеллас Фарма». Адрес: 109147, Москва, Марксистская ул., д. 16. ORCID: http://orcid.org/0000-0002-5014-9239; eLibrary SPIN: 4954-0700


Похожие статьи

К содержанию номера

Бионика Медиа