Economic analysis of Lixisenatide in Diabetes Mellitus Type 2

Usage of glucagon like peptide-1 receptors’ agonists (aGLP-1) is a new step in the treatment of Diabetes Mellitus Type 2 (DM 2). General attractive effects are positive effect on bodyweight, lower risk of hypoglycemia, compliance and possibility of combination with insulin or it’s analogues etc. Clinical-economic analysis of Lixisenatide in combination with insulin glargine has been performed for evaluation of reasons for state or insurance budgeting. Methods: Model of DM 2 has been used for comparison of Direct Costs (DC) of glargine+lixisenatid and basal bolus glargine+glulisine, detemir+aspart, glargine+aspart, glargine+lispro, detemir+lispro, detemir+glulisis as well as with combnations of metformin with exenatide or liraglutide. Efficacy criteria were amount of patient-years without complications during one-year period and amount of patient-years with targeted HbA1c level. Calculation cost has included: expenditures on pharmacotherapy of DM2 and complications, costs of out-patients aid, emergency and hospital treatment. Cost-efficacy ratio and incremental cost-efficacy rate as well Budget Impact have been performed. Results: Highest DC based on 2-year horizon of modelling were calculated for detemir+aspart -277 356 RUR, DC for glargine+lixisenatide was less on 5,6%. Costs of aGLP-1 and insulins were different, and expenditures on hypoglycemia too. Thus detemir+aspart were most expensive 77 763 RUR. Also in this group treatment of hypoglycemia was very costly. CERs (cost- effectiveness ratios) were 2 456 RUR, 3 752 RUR and 3 980 RUR. for glargine+glulisine, glargine+lixisenatide and detemir+aspart accordingly. Highest level of DC has been done for detemir+glulisine 281 628 RUR and detemir+lispro 278 744 RUR. Lixisenatide has led to insulin (glargine) dose reduction in compare with other combinations that reflected in less cost (54 186 RUR for glargine vs 81 289 RUR for detemir+glulisine during 2 years). Amount of patient-years with targeted level of HbA1c was the same in different treatment options but scheme glargine+lixisenatide was less costly DC among schemes with another aGLP-1 was less in glargine+lixisenatide on 65% in compare with metformin+liraglutide (741 531 RUR with 2-years of modelling horizon). Conclusion: Scheme glargine+lixisenatide more cost-saving regimen in compare with metformin+exenatide, metformin+liraglutide, detemir+short acting insulin analogues Scheme glargine+lixisenatide has not benefits in compare with glargine+glulisin but has less hypoglycemia level. Glargine+lixisenatide is an economic appropriate scheme for state (insurance) budgeting.

1. Дедов И.И., Шестакова М.В., Галстян Г.Р. и соавт. Инициация и интенсификация сахароснижающей терапии у больных сахарным диабетом 2 типа: обновление консенсуса совета экспертов Российской ассоциации эндокринологов (2015 г.) // Сахарный диабет. 2015;(1):5-23.

2. Дедов И.И., Омельяновский В.В. Шестакова М.В. и соавт. Сахарный диабет как экономическая проблема в Российской Федерации // Сахарный диабет. — 2016. — №1:30-43.

3. Инструкция по применению препарата Ликсумия®

4. Алгоритмы специализированной медицинской помощи больным сахарным диабетом Ред. И.И.Дедов, М.В.Шестакова. 7-й выпуск // Сахарный диабет. 2015;18(1S): 1-112.

5. Giorgino F., Bonadonna R.C., Gentile S., Vettor R. Treatment intensifi cation in patients with inadequate glycemic control on basal insulin: rationale and clinical evidence for the use of lixisenatide and other glucagon-like peptide-1 receptor agonists // Diabetes Metab Res Rev. — 2016;-32(1):51-59.

6. Rosenstock J., Raccah D., Korányi L. et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin // Diabetes Care. — 2013;36(10):2945-2951.

7. Kapitza C., Forst T., Coester H.V. et al. Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insuffi ciently controlled on metformin // Diabetes Obes Metab. — 2013;15(7):642-649.

8. Ahren B., Gautier J.F., Berria R. et al. Pronounced reduction of postprandial glucagon by lixisenatide: a meta-analysis of randomized clinical trials // Diabetes, Obesity and Metabolism. 2014;16:861—868.

9. Charbonnel B., Bertolini M., Tinahones F. et al. Lixisenatide plus basal insulin in patients with type 2 diabetes mellitus: a meta-analysis // J Diabetes Compl. — 2014;28(6):880-886.

10. Raccah D., Lin J., Wang E. et al. Once-daily prandial lixisenatide versus once-daily rapid-acting insulin in patients with type 2 diabetes mellitus insuffi ciently controlled with basal insulin: analysis of data from fi ve randomized, controlled trials // J Diabetes Compl. — 2014;28(1):40-44.

11. Meier J., Rosenstock J., Hincelin-M´ery A. et al. Contrasting effects of Lixisenatide and Liraglutide on postprandial glycemic control, gastric emptying, and safety parameters in patients with type 2 Diabetes on optimized Insulin Glargine with or without Metformin: A Randomized, Open-Label Trial // Diabetes Care. — 2015; 38(7):1263-1273.

12. Колбин А.С., Хмельницкий О.К., Курылев А.А. и соавт. Первый в России опыт построения симуляционной модели исходов сахарного диабета 2 типа с дискретированным моделированием событий. Клинико-экономическая экспертиза. // Фармакоэкономика. — 2013;6(2):24-31.

13. Clarke P.M., Gray A.M., Briggs A. et al. A model to estimate the lifetime health outcomes of patients with type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model (UKPDS no. 68) // Diabetologia. — 2004;47(10):1747-1759.

14. Glycemic Control and Long-Term Eff ects of diabetes (EAGLE) model // Diabetes technology & therapeutics. — 2006;8(2):219-236.

15. Об утверждении отраслевого стандарта «Клинико-экономические исследования. общие положения» Приказ №163 Министерства Здравоохранения Российской Федерации от 27.05.2011.

16. Фармакоэкономика и фармакоэпидемиология — практика примемлемых решений / Ред. В.Б.Герасимов, А.Л.Хохлов, О.И.Карпов. — М.:Медицина, 2005. — 352с.

17. Walley T., Haycox A., Boland A. Pharmacoeconomics. Elsevier Health Sciences, 2004. — 216р.

18. Kirk J., Craven T., Lipkin E. et al. Longitudinal changes in dietary fat intake and associated changes in cardiovascular risk factors in adults with type 2 diabetes: The ACCORD trial // Diabetes Res Clin Pract. — 2013;100(1): 61—68.

19. Khunti K., Alsifri S., Aronson R., et al. Self-reported hypoglycaemia: a global study of 24 countries with 27,585 insulin-treated patients with diabetes: the HAT study. Diabetologia 2014; 57 Suppl: S201-202.

20. Malek R., Ajili F., Assaad-Khalil S.H., et al. Similar glucose control with basal-bolus regimen of insulin detemir plus insulin aspart and thrice-daily biphasic insulin aspart 30 in insulin-naive patients with type 2 diabetes: Results of a 50-week randomized clinical trial of stepwise insulin intensifi cation // Diabetes Metab. 2015;41(3):223-230.

21. Постановление Правительства России от 19 декабря 2015 г. №1382 «О программе государственных гарантий бесплатного оказания гражданам медицинской помощи на 2016 год и на плановый период 2017 и 2018 годов» http://www.garant.ru/products/ipo/prime/doc/71189846/ Дата обращения: 23.01.16.

22. Электронный ресурс http://www.spboms.ru/kiop/main?page_id=338 (дата обращения 03.01.2016).

23. ATC/DDD Index 2015. — http://www.whocc.no/atc_ddd_index/ (дата обращения: 30.12.2015).

24. Rosenstock J., Davies M., Home P.D. et al. A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes // Diabetologia 2008; 51(3):408—416.

25. Swinnen S.G., Dain M.P., Aronson R. et al. A 24-week, randomized, treat-to-target trial comparing initiation of insulin glargine once-daily with insulin detemir twice-daily in patients with type 2 diabetes inadequately controlled on oral glucose-lowering drugs. Diabetes. Care 2010; 33(6): 1176—1178.

26. Белоусов Д.Ю., Афанасьева Е.В. Базальные аналоги инсулина в контроле сахарного диабета 2 типа — экономические аспекты. // Качественная клиническая практика. — 2014. — №1. — C.3-13.

27. Аметов А.С., Белоусов Д.Ю. Фармакоэкономика инсулина гларгин при оптимизации инсулинотерапии сахарного диабета 2 типа. // Качественная клиническая практика. — 2012. — № 2. — C.4-11.

28. http;//grls.rosminzdrav.ru дата обращения к ресурсу 11 января 2016 г. 29. http://medlux.ru дата обращения 11 января 2016 г.