Clinical and economic efficiency of treatment with dapagliflozin of patients with type 2 diabetes mellitus in Russian health care conditions

Purpose. To evaluate pharmacoeconomic efficiency of dapagliflosin application for intensification of hypoglycemic therapy — in comparison with addition to therapy of group of inhibitors of dipeptidyl peptidase 4 (iDPP-4) or basal insulin. Materials and methods. Budget impact analysis was done retrospectively using published clinical research data. The evaluation was carried out according to 2 scenarios of intensification of therapy of patients with diabetes mellitus: using dapagliflozine in comparison with iDP-4 (scenario No. 1) or using dapagliflozine in comparison with basal insulins (scenario No. 2). In the first scenario, both direct and indirect costs were taken into account, and in the second scenario, only direct costs were taken into account. Results. The analysis of influence on the budget showed that when using a dapagliflozin in comparison with medicines of class IDPP-4 it is possible to reach decrease in the total costs on the 2nd year of therapy, at the same time in 5 years economy will make 19.4-24.2 % or 21,985-29,123 rub per 1 patient. In patients who have not previously received insulin, with the same effectiveness in reducing the level of glycated hemoglobin, the use of dapagliflosin in comparison with basal insulin reduces the cost of drug therapy by 9.3 % or by 3,566 rubles per year. If combined «surrogate» endpoint is used as an efficiency criterion, reduction of glycated hemoglobin level and body weight, intensification of therapy using dapagliflosin is dominant scheme: More patients reach the end point on dapagliflozine compared to basal insulin (57 and 37 % respectively), with direct costs associated with using dapagliflozine less by 9.3 % or 1,763 rubles in 180 days. Conclusion. The use of dapagliflosin to intensify therapy in patients with diabetes mellitus is economically viable. From the point of view of pharmacoeconomics, therapy schemes involving dapagliflosin dominate comparison therapy schemes. Dapagliflosin can be recommended for inclusion in medical care standards, drug programs, and formula lists of medical organizations.

clinical and economic analysis, dapagliflozin, budget impact analysis, intensification of hypoglycemic therapy, diabetes mellitus

1. Standards of specialized diabetes care. 9th Edition. Ed by Dedov II, Shestakova MV, Mayorov AYu. Moscow: Diabetes mellitus; 2019. (In Russ). DOI:10.14341/DM221S1.

2. Dedov II, Shestakova MV, Vikulova OK, Zheleznyakova AA, Isakov MA. 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. Diabetes Mellitus. 2018;21(3):144-159. (In Russ). DOI: 10.14341/DM9686.

3. Cosentino F, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020 Jan 7;41(2):255-323. DOI: 10.1093/eurheartj/ehz486.

4. Davies MJ, et al. 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). Diabetes Care. 2018 Dec;41(12):2669-2701. DOI: 10.2337/dci18-0033.

5. Wanner C, et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N. Engl. J. Med. (2016). DOI:10.1056/NEJMoa1515920.

6. Neal B, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. DOI: 10.1056/NEJMoa1611925.

7. Wiviott SD, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019 Jan 24;380(4):347-357. DOI: 10.1056/NEJMoa1812389.

8. Zelniker TA, et al. Comparison of the Effects of Glucagon-Like Peptide Rece onists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis of Cardiovascular Outcomes Trials. Circulation. 2019 Apr 23;139(17):2022-2031. DOI: 10.1161/CIRCULATIONAHA.118.038868.

9. Zelniker TA, 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 Jan 5;393(10166):31-39. DOI:10.1016/S0140-6736(18)32590-X.

10. McMurray JJV, et al. A trial to evaluate the effect of the sodium—glucose co?transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA?HF). Eur J Heart Fail. 2019 May;21(5):665-675. DOI: 10.1002/ejhf.1432.

11. Gosudarstvennyj reestr lekarstvennyh sredstv. Instrukciya po medicinskomu primeneniyu preparata Forsiga (dapagliflozin), ЛП-002596. (In Russ). Available at: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=0be604a2-bf33-4a1e-9fd2-4ae2e2066da5&t=. (Accessed: 8th November 2019).

12. Wilding JP, et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med. 2012 Mar 20;156(6):405-15. DOI: 10.7326/0003-4819-1566-201203200-00003.

13. Das G, Surya A & Abusahmin H. Use of dapagliflozin as an add-on to insulin therapy in patients with suboptimally controlled type 2 diabetes. Ther Adv Endocrinol Metab. 2018 25;9(8):269-270. DOI: 10.1177/2042018818771434.

14. 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 Feb;20(2):344-351 DOI:10.1111/dom.13077.

15. Dohody-Federal’naya sluzhba gosudarstvennoj stastiki. (In Russ)..

16. Dedov II, Shestakova MV, Vikulova OK, Zheleznyakova AV & Isakov MА. Diabetes mellitus in Russian Federation: prevalence, morbidity, mortality, parameters of glycaemic control and structure of glucose lowering therapy according to the Federal Diabetes Register, status 2017. Diabetes Mellitus. 2018;21(3):144-159. DOI: 10.14341/DM9686.

17. WHO. Defined Daily Dose (DDD) — WHO: A10A INSULINS AND ANALOGUES. WHO Collaborating Centre for Drug Statistics Methodology (2018). Available at: https://www.whocc.no/atc_ddd_index/?code=A10AE04&showdescription=yes. (Accessed: 28th November 2019).

18. Zinman B, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. DOI: 10.1056/NEJMoa1504720.

19. Leiter LA, McGuire DK & Wilding JPH. Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction. Subanalysis From the DECLARETIMI 58 Trial. Circulation. 2019 May 28;139(22):2516-2527 DOI:10.1161/CIRCULATIONAHA.119.039996.

20. White WB, et al. Alogliptin after Acute Coronary Syndrome in Patients with Type 2 Diabetes. N Engl J Med. 2013 Oct 3;369(14):1327-35. DOI:10.1056/NEJMoa1305889.

21. Scirica BM, et al. Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus. N Engl J Med. 2013 Oct 3;369(14):1317-26. DOI:10.1056/NEJMoa1307684.

22. Green JB, et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015 Jul 16;373(3):232-42. DOI: 10.1056/NEJMoa1501352.

23. Kostev K, Pscherer S, Rist R, et al. Changes in Glycemic Control and Body Weight After Initiation of Dapagliflozin or Basal Insulin Supported Oral Therapy in Type 2 Diabetes: A Primary Care Database Study. J Diabetes Sci Technol. 2017 05 4;11(3):590-596.

24. The ORIGIN Trial Investigators, et al. Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia. N Engl J Med. 2012 Jul 26;367(4):319-28. DOI: 10.1056/NEJMoa1203858

25. Marso SP, et al. Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes. N Engl J Med. 2017 Aug 24;377(8):723-732. DOI: 10.1056/NEJMoa1615692.

26. Mosenzon O, et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes?: an analysis from the DECLARE — TIMI 58 randomised trial. LANCET Diabetes Endocrinol. 2019 Aug;7(8):606-617. DOI: 10.1016/S2213-8587(19)30180-9.

27. Furtado RHM, et al. Dapagliflozin and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Prior Myocardial Infarction: A Sub-analysis From DECLARE TIMI-58 Trial. Circulation. 2019 May 28;139(22):2516-2527. DOI: 10.1161/CIRCULATIONAHA.119.039996.

28. Mcmurray JJV, Ponikowski P, Bolli GB & Lukashevich V. Effects of Vildagliptin on Ventricular Function in Patients With Type 2 Diabetes Mellitus and Heart Failure. JACC: Heart Failure 6(1) 2017. DOI: 10.1016/j.jchf.2017.08.004.

29. Nissen SE, et al. Alogliptin after Acute Coronary Syndrome in Patients with Type 2 Diabetes. N Engl J Med. 2013;1—9. DOI: 10.1056/NEJMoa1305889.