Health technology assessement of the fxed combination of insulin glargine 100 UI/ml and lixisenatide in the treatment intensifcation of diabetes mellitus type 2

Fixed antidiabetic drugs’ combinations have aim to improve of Diabetes Mellitus type 2 (DMT2) control as well as a safety treatment increasing. Soliqua SoloStar® is a new registered drug for control of fasting and prandial glucose levels, contained insulin glargine 100 UI/ml and lixisenatide. In the published non-direct comparison, it was more effective for DMT2 control vs insulin glargine 100 UI/ml and lixisenatide separately, and daily insulin dose was less on 22 UI.

Aim: To evaluate of Soliqua SoloStar® reasonability og inclusion from pharmacoeconomics point of view into the State program of the free medical Aid guarantees.

Materials and methods: Retrospective comparative economic analysis based on the published data of new methodology treatment with Soliqua SoloStar® in compare with the current treatment methodology with usage of insulin glargine and lixisenatide separately. Common used methodology of clinical-economic analysis was used, and target group of patients was created based on the Federal Diabetes Register. Direct medical cost was defned as a cost of medications. Differentiation between direct medical cost for the proposed methodology and current practice of the separate usage of insulin glargine and lixisenatide was calculated. Discounting at 5 % annually used in the calculation of the three years time horizon. Te results of health technology assessment are confrmed by sensitivity analysis. Microsof Excel was used for calculation.

Results: Calculation has been performed for two pens of Soliqua SoloStar® with different prices (Variation 1 and 2) in compare with different drugs of insulin glargine 100 UI/ml and lixisenatide. Soliqua SoloStar® had less daily dose (by insulin glargine) on 22 UI vs free combination, and dose of lixisenatide was 20 mkg per day. Amount of patients who have reached HbA1c<7 % was higher in Soliqua group vs free combination group on 29 % (95 % CI: 20.2-30.7; p<0.0001). Cost of daily dose in Variation 1 is 269.72 RUR., for Variation 2 — 214.28 RUR. In the same time cost of the free combination of insulin glargine 100 UI and lixisenatide is depended from trade’s name of the drug, while cost of lixisenatide per day is the same for free combination and has 158.8 RUR. Soliqua SoloStar® usage can decrease budget impact in comparison with free combination on 10.46-35.02 % (depending on cost of insulin glargine 100 UI from different manufacturers and Soliqua pen cost). Cost-effectiveness analysis has shown that Soliqua SoloStar® had economic advantages in compare with free components’ combination on 51.95-65.08 % (depending on cost of insulin glargine 100 UI from different manufacturers and variations of Soliqua pen cost).

Conclusion: Soliqua SoloStar® has pharmacoeconomics evidences to be included into the Governmental program of free medical Aid in Diabetes Mellitus type 2.

1. World Health Organization. Global report on diabetes: executive summary. http://apps.who.int/iris/bitstream/10665/204874/1/WHO_NMH_NVI_16.3_eng.pdf. appeal to the resource 16.10.2018.

2. Dedov II, Shestakova MV, Galstyan GR. Te prevalence of type 2 diabetes mellitus in the adult population of Russia (NATION study). Diabetes Mellitus. 2016;19(2):104—112 (In Russ). DOI: 10.14341/DM2004116-17

3. Dedov II, Kontsevaya AV, Shestakova MV, et al. Economic evaluation of type 2 diabetes mellitus burden and its main cardiovascular complications in the Russian Federation. Diabetes mellitus. 2016;19(6):518—527. (In Russ). DOI: 10.14341/DM8153

4. Dedov II, Kalashnikova MF, Belousov DY, et al. Cost-of-Illness Analysis of Type 2 Diabetes Mellitus in the Russian Federation: Results from Russian multicenter, observational, pharmacoepidemiologic study of diabetes care for patients with type 2 diabetes mellitus (FORSIGHT-Т2DM). Diabetes mellitus. 2017;20(6):403—419. (In Russ). DOI: 10.14341/DM9278

5. Dedov II, Shestakova MV, Ametov AS, et al. Russian Association of Endocrinologists expert consensus document on initiation and intensifcation of antyhyperglycaemic therapy in type 2 diabetes mellitus. Diabetes mellitus. 2011;4:6—7. (In Russ).

6. Kontsevaya A, Karpov O, Shestakova M. Belousov Y. Economic evaluation of diabetes mellitus type 2 burden and it’s main cardiovascular complications in the Russian Federation. Value in Health. 2017;20:A374.

7. American Diabetes Association. Standards of medical care in diabetes—2017. Diabetes Care. 2017;40(suppl 1):S1-S135.

8. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140—149.

9. Garber AJ, Abrahamson MJ, Barzilay JI, et al. AACE/ACE Comprehensive Diabetes Management Algorithm 2016. Endocr Pract. 2016;22(1):84—113. DOI: 10.4158/EP151126.CS

10. Standards of specialized diabetes care. Ed by Dedov II, Shestakova MV, Mayorov AY. 8th Edition. Moscow: UP PRINT; 2017. (In Russ). DOI: 10.14341/DM20171S8

11. Khunti K, Nikolajsen A, Torsted BL, et al. Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin. Diabetes Obes Metab. 2016;18(4):401—409. DOI: 10.1111/dom.12626

12. Montvida O, Shaw J, Atherton JJ, et al. Long-term trends in antidiabetes drug usage in the U.S.: Real-world evidence in patients newly diagnosed with Type 2 Diabetes. Diabetes Care. 2018;41(1):69—78. DOI: 10.2337/dc17-1414

13. Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Eye Study Group and the Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Study Group. Persistent effects of intensive glycemic control on retinopathy in type 2 diabetes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) follow-on study. Diabetes Care. 2016;39(7):1089—1100. DOI: 10.2337/dc16-0024

14. Heise T, Mathieu C. Impact of the mode of protraction of basal insulin therapies on their pharmacokinetic and pharmacodynamic properties and resulting clinical outcomes. Diabetes Obes Metab. 2017;19(1):3—12. DOI: 10.1111/dom.12782

15. Davidson JA. Differential effects of prandial and non-prandial GLP-1 receptor agonists in type 2 diabetes therapy. Postgrad Med. 2015;127(8):827— 841. DOI: 10.1080/00325481.2015.1096743

16. Eng C, Krammer CK, Zinman B, et al. Glucagonlike peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis. Lancet. 2014;384(9961):2228— 2234. DOI: 10.1016/S0140-6736(14)61335-0

17. Ahren B, Gautier JF, Berria R, et al. Pronounced reduction of postprandial glucagon by lixisenatide: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2014;16(9):861—868. DOI: 10.1111/dom.12290

18. Kolbin A, Mosikyan A, Kurilev A. Economic analysis of Lixisenatide in Diabetes Mellitus Type 2. Kachestvennaya klinicheskaya praktika. 2015;4:53—66. (In Russ).

19. Instrukciya po medicinskomu primeneniyu preparata Solikva SoloStar®. (In Russ). http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid appeal to the resource 17.10. 2018.

20. Meier J. Titratable fxed-ratio versus sequential combination of insulin glargine and lixisenatide in type 2 diabetes uncontrolled on basal insulin. Poster №808 presented at the 53rd Annual Meeting of the European Association for the Study of Diabetes (EASD); 11—15 September 2017 Lisbon, Portugal.

21. Rosenstock J, Handelsman Y, Vidal J, et al. Propensity score?matched comparative analyses of simultaneously administered fxed?ratio iGlarLixi (LixiLan) vs sequential administration of insulin glargine and lixisenatide in uncontrolled type 2 diabetes. Diabetes Obes Metab. 2018 Jul 4. DOI: 10.1111/dom.13462

22. Farmakoe`konomika i farmakoe`pidemiologiya — praktika priemlemy`x reshenij. Ed by V.B. Gerasimov, A.L. Xoxlov, O.I. Karpov. Moscow: Meditsina; 2005 (In Russ).

23. Metodicheskie rekomendacii po provedeniyu sravnitel`noj klinikoe`konomicheskoj ocenki lekarstvennogo preparata. Moscow: FGBU «Centr e`kspertizy` i kontrolya kachestva medicinskoj pomoshhi»; 2016. (In Russ).

24. http://grls.rosminzdrav.ru, appeal to the resource 17.10.2018 г.

25. Metodicheskie rekomendacii po ocenke vliyaniya na byudzhet v ramkax realizacii programmy` gosudarstvenny`x garantij besplatnogo okazaniya grazhdanam medicinskoj pomoshhi. Moscow: FGBU «Centr e`kspertizy` i kontrolya kachestva medicinskoj pomoshhi»; 2016. (In Russ).

26. Peyrot M, Rubin RR, Kruger DF, Luther LB. Correlates of insulin injection omission. Diabetes Care. 2010;33(2):240—245. DOI: 10.2337/dc09-1348

27. World Health Organization (2003): Adherence to long-term therapies, evidence for action. Geneva: (Elektronic resourse). Access mode: http://www.who.int2. appeal to the resource 07.11.2018.

28.