Role of sodium-glucose co-transporter type 2 inhibitor dapagliflozin in prevention of cardiovascular complications in patients with diabetes mellitus type 2

• Valentin V. Fadeev

Abstract

Medical science is shaping more complex approach to health. One example of this trend is helping a patient with type 2 diabetes. Against the background of increasing life expectancy, the spread of metabolic disorders, cardiovascular diseases and renal dysfunction intensifying. Consequently the patient's treatment should be carried out, taking into account multiple risk factors and organ impairments. In this regard, recent studies in the group of sodium-glucose co-transporter type 2 inhibitors demonstrate that the specialist's arsenal is replenished with sugar-lowering drugs that demonstrate cardio- and nephroprotective properties.

On the side of the cardiovascular component of the problem, heart failure plays a key role for a patient with type 2 diabetes. According to international studies, the diagnostics of this disease remains insufficient, which is also true for the Russian Federation, where heart failure is the main cause of death in these patients.

To date, a large evidence base has been collected on the dapagliflozin for the treatment of patients with heart failure. The DECLARE-TIMI 58 study demonstrated a reduced risk of hospitalization for heart failure in both patients with a history of cardiovascular disease and risk factors. In addition to primary prevention in DECLARE-TIMI 58, in the DAPA-HF study, dapagliflozin had shown effectiveness in preventing cardiovascular death or hospitalization for heart failure or urgent heart failure visit in patients diagnosed with heart failure with a reduced ejection fraction.

Keywords:diabetes mellitus, heart failure, dapagliflozin, SGLT-2i, DECLARE-TIMI 58, DAPA-HF, CVD-real, CKD, comorbidity, complications of diabetes, hypoglycemic, cardioprotection, nephroprotection

References

1. IDF Diabetes Atlas. 9^th ed. International Diabetes Federation, 2019. URL: https://www.diabetesatlas.org/en/ (date of access May 08, 2020)

2. Dedov I.I., Shestakova M.V., Galstyan G.R. The prevalence of type 2 diabetes mellitus in the adult population of Russia (NATION study). Sakharniy diabet [Diabetes Mellitus]. 2016; 19 (2): 104-12. DOI: 10.14341/DM2004116-17 (in Russian)

3. Dedov I.I., Shestakova M.V., Mayorov A.Y., et al. (eds). Standards of specialized diabetes care. 9th ed. Sakharniy diabet [Diabetes Mellitus]. 2019; 22 (S 1-1): 1-144. DOI: 10.14341/DM221S 1 (in Russian)

4. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020; 41 (2): 255-23. DOI: 10.1093/eurheartj/ehz486

5. Shah A.D., Langenberg C., Rapsomaniki E., Denaxas S., Pujades-Rodriguez M., Gale C.P., et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 19 million people. Lancet Diabetes Endocrinol. 2015; 3 (2): 105-13. DOI: 10.1016/S 2213-8587(14)70219-0

6. Petunina N.A., Trukhin I.V., Trukhina L.V., Sizova Z.M., Zakharova V.L. Heart failure and diabetes mellitus: insight into comorbidity. Sakharniy diabet [Diabetes Mellitus]. 2019; 22 (1): 79-87. DOI: 10.14341/ DM9784 (in Russian)

7. Bell DSH. Heart Failure: The frequent, forgotten, and often fatal complication of diabetes. Diabetes Care. 2003; 26 (8): 2433-41. DOI: 10.2337/diacare.26.8.2433

8. Kannel W.B., Hjortland M., Castelli W.P. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974; 34 (1): 29-34. DOI: 10.1016/0002-9149(74)90089-7

9. Shestakova M.V. DECLARE-TIMI 58 trial in the context of EMPA-REG OUTCOME and CANVAS. Sakharniy diabet [Diabetes Mellitus]. 2019; 22 (6): 592-601. DOI: 10.14341/DM10289 (in Russian)

10. Nichols G.A., Gullion C.M., Koro C.E., et al. The incidence of congestive heart failure in type 2 diabetes: an update. Diabetes Care. 2004; 27 (8): 1879-84. DOI: 10.2337/diacare.27.8.1879

11. Faden G., et al. The increasing detection of asymptomatic left ventricular dysfunction in patients with type 2 diabetes mellitus without overt cardiac disease: data from the SHORTWAVE study. Diabetes Res Clin Pract. 2013; 101: 309-16.

12. Boonman-de Winter L.J., et al. High prevalence of previously unknown heart failure and left ventricular dysfunction in patients with type 2 diabetes. Diabetologia. 2012; 55: 2154-62. DOI: 10.1007/s00125-012-2579-0

13. Wu B., et al. Understanding CKD among patients with T2DM: prevalence, temporal trends, and treatment patterns - NHANES 2007-2012. Article and supplementary tables. BMJ Open Diabetes Res Care. 2016; 4 (1): e000154.

14. Shamkhalova M.S., Vikulova O.K., Zheleznyakova A.V., Isakov M.A., Shestakova M.V., Dedov I.I. Trends in the epidemiology of chronic kidney disease in Russian Federation according to the Federal Diabetes Register (2013-2016). Sakharniy diabet [Diabetes Mellitus]. 2018; 21 (3): 160-9. DOI: 10.14341/DM9392 (in Russian)

15. Foley R.N., et al. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol. 2005; 16: 489-95.

16. Dedov I.I., Shestakova M.V., Vikulova O.K., Zheleznyakova A.A., Isakov M.A. Diabetes mellitus in Russian Federation: prevalence, morbidity, mortality, parameters of glycaemic control and structure of hypoglycaemic therapy according to the Federal Diabetes Register, status 2017. Sakharniy diabet [Diabetes Mellitus]. 2018; 21 (3): 144-59. DOI: 10.14341/DM9686. (in Russian)

17. Dedov I.I., Shestakova M.V., Vikulova O.K., Zheleznyakova A.V., Isakov M.A. Atlas of the diabetes registry of the Russian Federation, status 2018. Sakharniy diabet [Diabetes Mellitus]. 2019; 22 (S 2-2): 4-61. (in Russian)

18. Bertoni A.G., et al. Heart failure prevalence, incidence, and mortality in the elderly with diabetes. Diabetes Care. 2004; 27: 699-703. DOI: 10.2337/diacare.27.3.699

19. Kato M. The concept of heart failure: chronic diseases accompanied by an attack of acute exacerbation. In: Sato N. (ed.). Therapeutic Strategies for Heart Failure. Tokyo, Japan: Springer, 2018: 1-15.

20. Tuppin P., et al. Two-year outcome of patients after a first hospitalization for heart failure: A national observational study. Arch Cardiovasc Dis. 2014; 107: 158-68. DOI: 10.1016/j.acvd.2014.01.012

21. White W.B., et al. Cardiovascular mortality in patients with type 2 diabetes and recent acute coronary syndromes from the EXAMINE trial. Diabetes Care. 2016; 39 (7): 1267-73. DOI: 10.2337/dc16-0303

22. Pharmacologic approaches to glycemic management: standards of medical care in diabetes - 2020. Diabetes Care. 2020; 43 (1): S 98-110. DOI: 10.2337/dc20-S 009

23. Buse J.B., 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: 221-8. DOI: 10.2337/dci19-0066

24. Scirica B.M., et al.; SAVOR-TIMI 53 Steering Committee and Investigators. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2015; 132: e198.

25. Seferovic P., et al. Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur Heart Fail. 2018; 20: 853-72. DOI: 10.1002/ejhf.1170

26. White W.B., et al. DPP-4 inhibitors and risk of heart failure EXAMINE. N Engl J Med. 2013; 369: 1327-35. DOI: 10.1016/S 0140-6736(15)60037-X

27. Green J.B., et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015; 373: 232-42. DOI: 10.1056/NE-JMoa1501352

28. Rosenstock J., et al. Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: rationale for the active-comparator CAROLINA trial. Diabet Vasc Dis Res. 2013; 10: 289-301. DOI: 10.1177/1479164112475102

29. Rosenstock J., et al. Effect of Linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk. JAMA. 2019; 321 (1): 69-79. DOI: 10.1001/jama.2018.18269

30. Kristensen S.L., et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; 7: 776-85. URL: 10.1016/S 2213-8587(19)30249-9

31. Zelniker T.A., 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 (10 166): 31-9. DOI: 10.1016/ S 0140-6736(18)32590-X

32. Verma S., Jdni P., Mazer C.D. Comment Pump, pipes, and filter: do SGLT2 inhibitors cover it all? Lancet. 2019; 393 (10 166): 3-5. DOI: 10.1016/S 0140-6736(18)32824-1

33. Wiviott S.D., et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019; 380: 347-57. DOI: 10.1056/NE-JMoa1812389

34. Zinman B., et al. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME™), Cardiovasc Diabetol. 2014; 13: 102. DOI: 10.1186/1475-2840-13-102

35. Neal M.B., et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017; 377: 644-57. DOI: 10.1056/NE-JMoa1611925

36. Forxiga. Instructions for medical use (film-coated tablets, 5 mg, 10 mg). Registration certificate LP-002596 from 24.12.2019. (in Russian)

37. McMurray J.J.V., et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019; 381: 1995-2008. DOI: 10.1056/NEJMoa1911303

38. Petrie M.C., et al. Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes. JAMA. 2020; 323 (14): 1353-68. DOI: 10.1001/ jama.2020.1906

39. Verma S., McMurray J.J.V. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018; 61 (10): 2108-17. DOI: 10.1007/s00125-018-4670-7

40. Bertero E., Prates Roma L., Ameri P., et al. Cardiac effects of SGLT2 inhibitors: the sodium hypothesis. Cardiovasc Res. 2018; 114 (1): 12-8. DOI: 10.1093/cvr/cvx149

41. Staels B. Cardiovascular protection by sodium glucose cotransporter 2 inhibitors: potential mechanisms. Am J Med. 2017; 130 (6S): S 30-9. DOI: 10.1016/j.amjmed.2017.04.009

42. Persson F., et al. Dapagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in people with type 2 diabetes (CVD-REAL Nordic) when compared with dipeptidyl peptidase-4 inhibitor therapy: a multinational observational study. Diabetes Obes Metab. 2018; 20 (2): 344-51. DOI: 10.1111/dom.13077

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)