Preview

FARMAKOEKONOMIKA. Modern Pharmacoeconomic and Pharmacoepidemiology

Advanced search

Availability and Pharmacoeconomics of Insulin Therapy in Countries with the Largest Number of Diabetics

https://doi.org/10.17749/2070-4909.2019.12.3.178-190

Full Text:

Abstract

The aim of the review was to analyze the availability of insulin therapy and the ways to improve it in countries with the largest number of patients with diabetes. It was also aimed to assess the medical, social and economic importance of insulin therapy and industrial production of therapeutic recombinant insulin.

Materials and methods. The analysis was based on the data taken from monographs and publications in peer-reviewed journals, reports of companies and medical organizations, and the information available in the Internet. The demand and supply in the market of recombinant therapeutic insulin, the insulin market segmentation, and the costs for insulin replacement therapy in countries with the largest number of patients with diabetes were studied.

Results and discussion. The pro- and contra- arguments regarding the import of insulin and its impact on the national budget are presented. Technological specifics of recombinant insulin production are discussed; the funding and investments in the biopharmaceutical sector are analyzed. The benefits of industrial production of recombinant therapeutic insulin and its impact on the regional and national economy are demonstrated.

Conclusion. The availability of therapeutic insulin in most countries with the largest number of diabetics is unsatisfactory and needs a radical improvement. By analyzing the economic aspects of diabetes and the pharmacoeconomics of insulin, it is advised to develop a modern management system for insulin replacement therapy, especially in countries with large numbers of diabetics. The use of innovative technologies will reduce the production costs of recombinant therapeutic insulin, increase the availability of insulin therapy and thereby improve the quality of life in diabetic patients. Evidence that the production of therapeutic insulin has a positive effect not only on the healthcare, but on the socio-economic situation in the region is also provided. Countries with a number of diabetics exceeding 5 million are encouraged to launch their own production of recombinant therapeutic insulin. The results of the present analysis confirm that half of them are able to manufacture adequate human insulin and/or its analogues.

 

About the Author

S. V. Ponomarenko
SophiGen, Insu-Pharma AG
Germany
Project Manager


References

1. Guidelines on second- and third-line medicines and type of insulin for the control of blood glucose levels in non-pregnant adults with diabetes mellitus. Geneva: World Health Organization. 2018.

2. Global report on diabetes. World Health Organization. Geneva. 2016.

3. Textbook of diabetes (ed by: Holt R. I.G, Cockram C. S., Flyvbjerg A., Goldstein B. J.) Fifth edition. Wiley-Blackwell. 2017. 1104 p.

4. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes – 2019. American Diabetes Association. Diabetes Care. 2019; 42 (S1): S13-S28. DOI: https://doi.org/10.2337/dc19-S002.

5. IDF DIABETES ATLAS Eighth edition. International Diabetes Federation. 2017; [Electronic resource] URL: https://www. diabetesatlas.org. Accessed: 03.07.2019.

6. Crasto W., Jarvis J., Davies M. J. Handbook of Insulin Therapies. Springer. 2016; 209 p.

7. Davies M. J., D’Alessio D.A., Fradkin j., Walter N. Kernan W. N., et al. Management of Hyperglycemia 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; 41: 2669-2701. DOI: https://doi.org/10.2337/dci18-0033.

8. Landgraf W., Sandow J. Recombinant Human Insulins – Clinical Efficacy and Safety in Diabetes Therapy. European Endocrinology. 2015; 12 (1): 1-6. DOI: 10.17925/EE.2016.12.01.12.

9. Bommer C., Sagalova V., Heesemann E., et al. Global Economic Burden of Diabetes in Adults: Projections From 2015 to 2030. Diabetes Care. 2018; 41 (5): 963-970. DOI: https://doi.org/10.2337/dc17-1962.

10. Cefallu W. T., Dawes D. E., Gavlak G., Goldman D., Herman W. H., et.al. Insulin Access and Affordability Working Group: Conclusions and Recommendations. Diabetes Care. 2018; 41 (6): 1299-1311. doi: 10.2337/dci18-0019.

11. Seuring T., Arachangel O., Suhrcke M. The economic costs of type 2 diabetes: A global systematic review. Pharm. Econ. 2015; 33: 811-831.

12. Beran D., Ewen M., Lepeska M., Laing R. Access to insulin: current challenges and constraints. Health Action International. 2017; [Electronic resource] URL: www.haiweb.org Accessed: 03.07.2019.

13. Ewen M, Joosse H-J, Beran D., Laing R. Insulin prices, availability and affordability in 13 low-income and middle-income countries. BMJ Global Health. 2019;4:e001410. [Electronic resource] URL: https://gh. bmj.com/content/bmjgh/4/3/e001410.full.pdf Accessed: 03.07.2019 doi:10.1136/bmjgh-2019-00141.

14. Maier K.,Riley M.ImprovingInsulinAccessandAffordability/ADA 2018; 1-15. [Electronic resource] URL: http://www.diabetes.org/ assets/pdfs/advocacy/improving-insulin-access-and.pdf. Accessed: 03.07.2019.

15. American Diabetes Association® Reaffirms Commitment to Insulin Access and Affordability for All – Transparency on Insulin Pricing Critical. 2018; [Electronic resource] URL: http://www.diabetes. org/newsroom/press-releases/2018/insulin-access-affordabilitytransparency-critical.html Accessed: 03.07.2019.

16. Beran D. The Rapid Assessment Protocol for Insulin Access (RAPIA): Research for Action on Access to Diabetes Care RG2004. 2009; [Electronic resource] URL: https://www.researchgate.net/ publication/228381768. Accessed: 03.07.2019.

17. Economic Costs of Diabetes in the U.S. in 2017. Diabetes Care. 2018; 41: 917-928. DOI: https://doi.org/10.2337/dci18-0007.

18. Pedron S., Emmert-Fees K., Laxy M., SchwettmannL. The impact of diabetes on labour market participation: a systematic review of results and methods. BMC Public Health. 2019; 19: 1-13. DOI: https://doi.org/10.1186/s12889-018-6324-6.

19. Kähm K., Laxy M., Schneider U., Rogowski W.H., Lhachimi S.K., Holle R. Health care costs associated with incident complications in patients with type 2 diabetes in Germany. Diabetes Care. 2018; 41: 971-978. DOI: https://doi.org/10.2337/dc17-1763.

20. Mbanya J. C., Sandow J., Landgraf W., OwensD.R. Recombinant Human Insulin in Global Diabetes Management – Focus on Clinical Efficacy. European Endocrinology. 2017; 13 (1): 21-25. DOI: https:// doi.org/10.17925/EE.2017.13.01.21.

21. Riddle M. C., Herman W. H. The Cost of Diabetes Cared An Elephant in the Room. Diabetes Care. 2018; 41: 929-932. DOI: https:// doi.org/10.2337/dci18-0012.

22. Ogurtsova K., J. D. Fernandes J. D., Huang Y., Linnenkamp U., et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Research and Clinical Practice. 2017; 128: 40-50.

23. Liebl A., Khunti K., Orozco-Beltran D., Yale J.-F. Health Economic Evaluation of Type 2 Diabetes Mellitus: A Clinical Practice Focused Review. Clinical Medicine Insights: Endocrinology and Diabetes. 2015; 8: 13-19. DOI:10.4137/CMED.S20906.

24. Petrides D. Bioprocess Design and Economics. Bioseparations Science and Engineering 2nd Edition (ed by: Harrison R. G., Todd P. W., Rudge S. R., Petrides D. P.). Oxford University Press. 2015; 11.1-11.83.

25. Rotenstein K. S., Ran N. R., Shivers J. P., Yarchoan M., Close K. L. Opportunities and Challenges for Biosimilars: What’s on the Horizon in the Global Insulin Market? Clinical Diabetes. 2012; 30 (4): 138-150.

26. Wirtz V. J. Insulin Market Profile 2016. Amsterdam: Health Action International: 104 p. [Electronic resource] URL: https://haiweb. org/wp-content/uploads/2016/04/ACCISS_Insulin-Market-Profile_ FINAL.pdf. Accessed: 03.07.2019.

27. Assessment report EMA/CHMP/340840/2014. Abasria/ International non-proprietary name: insulin glargine Procedure No. EMEA/H/C/002835/0000. [Electronic resource] URL: https://www. ema.europa.eu/en/documents/assessment-report/abasria-eparpublic-assessment-report_en.pdf. Accessed: 03.07.2019.

28. Mylan and Biocon Announce Regulatory Submission for Insulin Glargine Accepted for Review by European Medicines Agency 2016. [Electronic resource] URL: http://newsroom.mylan.com/2016-11-03-Mylan-and-Biocon-Announce-Regulatory-Submission-for-Insulin-Glargine-Accepted-for-Review-by-European-Medicines-Agency Accessed: 03.07.2019.

29. Merck Announces U. S. FDA Filing Acceptance of New Drug Application (NDA) for MK-1293, an Investigational Follow-On Biologic Insulin Glargine 2016. [Electronic resource] URL: https://www. mrknewsroom.com/news-release/research-and-development-news/ merck-announces-us-fda-filing-acceptance-new-drug-application Accessed: 03.07.2019.

30. Ewen M., Joosse H.-J., Ashigbie P., Beran D., Laing R. Insulin Prices Profile. 2016: 155 p. Amsterdam: Health Action International. [Electronic resource] URL: www.haiweb.org. Accessed: 03.07.2019.

31. Kuhlmann M. K., Schmidt A. Production and manufacturing of biosimilar insulins: implications for patients, physicians, and health care systems. Biosimilars. 2014; 4: 45-48.

32. Davies M., Dahl D., Heise T., Kiljanski J., Mathieu C. Introduction of biosimilar insulins in Europe. Diabet. Med. 2017; 34: 1340-1353.

33. Sandow J., Landgraf W., Becker R., Seipke G. Equivalent Recombinant Human Insulin Preparations and their Place in Therapy Diabetes. European Endocrinology. 2015; 11 (1): DOI: 10.17925/ EE.2015.11.01.10.

34. Derwahl K. M., Bailey T. S., Wernicke-Panten K., Ping L., Pierre S. Efficacy and Safety of Biosimilar SAR342434 Insulin Lispro in Adults with Type 2 Diabetes, Also Using Insulin Glargine: SORELLA 2 Study. DTT. 2018; 20 (1): DOI: 10.1089/dia.2017.0281.

35. Owens D. R., Traylor L., Mullins P., Landgraf. W. Patient-level meta-analysis of efficacy and hypoglycaemia in people with type 2 diabetes initiating insulin glargine 100U/mL or neutral protamine Hagedorn insulin analysed according to concomitant oral antidiabetes therapy. Diabetes Res Clin Pract. 2017; 124: 57-65.

36. Tieu C., Lucas E. J., DePaola M., Rosman L., Alexander G. C. Efficacy and safety of biosimilar insulins compared to their reference products: A systematic review. PLoS ONE 2018; 13(4): e0195012. [Electronic resource] URL: https://journals.plos.org/plosone/ article?id=10.1371/journal.pone.0195012. Accessed: 03.07.2019. DOI: https://doi.org/10.1371/journal.pone.0195012.

37. Hua X., Carvalho N., Tew M., et al. Expenditures and Prices of Antihyperglycemic Medications in the United States: 2002-2013. JAMA. 2016; 315 (13): 1400-1402. DOI:10.1001/jama.2016.0126.

38. Holden S. E., Poole C. D., Morgan C. L., Currie C. J. Evaluation of the incremental cost to the National Health Service of prescribing analogue insulin. BMJ Open. 2011; 2: 1-7.

39. Heinemann L. Insulin Pens and New Ways of Insulin Delivery. DTT. 2013; 15: Supplement 1. S48-S59. DOI: 10.1089/dia.2013.1506.

40. Cafasso J. Insulin Prices: Pumps, Pens, Syringes, and More. 2018. [Electronic resource] URL: https://www.healthline.com/health/ type-2-diabetes/insulin-prices-pumps-pens-syringes Accessed: 03.07.2019.

41. Sorli C., Heile M. K. Identifying and meeting the challenges of insulin therapy in type 2 diabetes. J. Multidiscip. Healthcare. 2014; 7: 267-282.

42. Russell-Jones D., Gall M.-A., Niemeyer M., Diamant M., Del Prato S. Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: a meta-analysis of seven clinical trials. Nutr Metab Cardiovasc Dis. 2015; 25: 898-905.

43. Silva T.B.C., Almeida P.H.R.F., Araújo V.E., De Assis Acurcio F., et al. Effectiveness and safety of insulin glargine versus detemir analysis in patients with type 1 diabetes: systematic review and metaanalysis. Ther Adv Endocrinol Metab. 2018; 9(8): 241–254.

44. Hasslacher C., Bermejo J. L. Treatment with insulin analogs and prevalence of cardiovascular complications in patients with type 1 diabetes. Ther Adv Endocrinol Metab. 2017; 8 (11): 149-157. DOI: 10.1177/2042018817732732.

45. Bjekic´-Macut J., Zˇivkovic´ T.B., Kocic R. Clinical Benefit of Basal Insulin Analogue Treatment in Persons with Type 2 Diabetes Inadequately Controlled on Prior Insulin Therapy: A Prospective, Noninterventional, Multicenter Study. Diabetes Ther. 2018; 9: 651-662. https://doi.org/10.1007/s13300-018-0378-4.

46. Tricco A. C., Ashoor H. M., Antony J., Beyene J., et al. Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis. BMJ. 2014; 349: g5459. [Electronic resource] URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847127/ pdf/2046-4053-2-73.pdf. Accessed: 03.07.2019.

47. The Economic Impact of the U. S. Biopharmaceutical Industry: 2015 National and State Estimates. PhRMA_GoBOLDLY. 2017; Pharmaceutical Research and Manufacturers of America (PhRMA) special 301 submissial 2018. Washington, DC: PhRMA. 179 p.

48. Gurramkonda C., Polez S., Skoko N., Adnan A., Gabel T., et al. Application of simple fed-batch technique to high-level secretory production of insulin precursor using Pichia pastoris with subsequent purification and conversion to human insulin. Microbial Cell Factories. 2010; 9: 31-42. http://www.microbialcellfactories. com/content/9/1/31

49. Kroeff E. P., Owenes R. A., Campbell E. L., Johnson R. D., Marks H. I. Production scale purification of biosynthetic human insulin by reversed-phase high-performance liquid chromatography. Journal of Chromatography. 1989; 461: 45-61

50. Petrides D., Sapidou E., Calandranis J. Computer-Aided Process Analysis and Economic Evaluation for Biosynthetic Human Insulin Production – A Case Study. Biotechnol Bioeng. 1995; 48 (5): 529-541.

51. Krämer I., Sauer T. The new world of biosimilars: what diabetologists need to know about biosimilar insulins. British Journal of Diabetes & Vascular Disease. 2010; 10: 163-171.

52. Nilsson J., Jonasson P., Samuelsson E., Stähl S., Uhlen M. Integrated production of human insulin and its C-peptide. Journal of Biotechnology. 1996; 48: 241-250.

53. Gallegos J. E., Boyer C., Pauwels E., Kaplan W. A., Peccoud J. The Open Insulin Project: A Case Study for ‘Biohacked’ Medicines. Trends in Biotechnology. 2018; 36 (12): 1211-1218. DOI: https://doi. org/10.1016/j.tibtech.2018.07.009.

54. Baeshen N. A., Baeshen M. N., Sheikh A., Bora R. S., et al. Cell factories for insulin production. Microbial Cell Factories. 2014; 13: 141-149. http://www.microbialcellfactories.com/content/13/1/141.

55. Polez S., Origi D., Zahariev S., Guarnaccia C., Tisminetzky S. G., Skoko N., Baralle M. A Simplified and Efficient Process for Insulin Production in Pichia pastoris. PLOS ONE. 2016; 11 (12): 1-15.

56. Petrides D. P., Koulouris A., Lagonikos P. T. The Role of Process Simulation in Pharmaceutical Process Development and Product Commercialization. Ispe pharmaceutical engineering®. 2002; 22 (1): 1-8.

57. Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing. (Ed by Mollah H., Baseman H., Long M. John Wiley & Sons, Inc. 2013; 416 p.

58. Gulf Pharmaceutical Industries (Julphar) Insulin Production Facility. [Electronic resource] URL: https://www.pharmaceuticaltechnology.com/projects/gulf-pharmaceutical-industries-julpharinsulin-production-facility-uae/. Accessed: 03.07.2019.

59. Patent WO 2012/098009. Chimeric Polypeptide comprising a Membrane Protein and an Insulin Precursor. Ponomarenko S. Applicant GlucoMetrix AG. Priority Date: 21.01.2011; International Filling: 20.01.2012 PCT/EP2012/000266.

60. Kaplan W., Beall R. Insulin Patent Profile. Amsterdam: Health Action International. 2016.

61. Rasmussen B. Innovation and Commercialisation in the Biopharmaceutical Industry: Creating and Capturing Value. Edward Elgar Publishing Ltd. 2010; 326 p.

62. Anderlei T., Eibl D., Eibl R., Eisenkrätzer D. Facility of the Future. 2017. Dehema. 35 p.

63. Lütke-Eversloh T., Rogge P. Biopharmaceutical manufacturing in single-use Bioreactors. Current status and challenges from a CDMO perspective. Pharm. Ind. 2018; 80 (2): 281-284.

64. Gotham D., Barber M. J., Hill A. Production costs and potential prices for biosimilars of human insulin and insulin analogues. BMJ Glob Health. 2018; 3:e000850. [Electronic resource] URL: https://gh.bmj.com/content/bmjgh/3/5/e000850.full.pdf. Accessed: 03.07.2019. doi: 10.1136/bmjgh-2018-000850.

65. Seidenader N. Trend & market report. Insights into the diabetes- & insulin market. Brainnovative Consulting e.V. 2016; 32 p.

66. Lee J. PEST and NET analysis of biopharmaceutical industry. ICI Meeting 2015. [Electronic resource] URL: http://2015.icimeeting.com/ e-posters/pdf/22.pdf. Accessed: 03.07.2019.

67. Fernandes J., Zhang P. COST-EFFECTIVE AND COST-SAVING INTERVENTIONS FOR PREVENTION AND CONTROL OF DIABETES. Diabetes Voice. 2016; 62 (2): 16-20.

68. Pease A., Lo C., Earnest A., Liew D., Zoungas S. Evaluating optimal utilization of technology in type 1 diabetes mellitus from a clinical and health economic perspective: protocol for a systematic review. Systematic Reviews. 2018; 7: 44. DOI: https://doi.org/10.1186/ s13643-018-0706-9

69. Ourth H., Nelson J., Spoutz P., Morreale A. P. Development of a Pharmacoeconomic Model to Demonstrate the Effect of Clinical Pharmacist Involvement in Diabetes Management. J Manag Care Spec Pharm. 2018; 24 (5): 449-457.

70. Keeney E., Dawoud D., Dias S. Different Methods for Modelling Severe Hypoglycaemic Events: Implications for Effectiveness, Costs

71. and Health Utilities. PharmacoEconomics. 2018; 36: 523-532. DOI: https://doi.org/10.1007/s40273-018-0612-y.

72. Bailey T. S., Walsh J., Stone J. Y. Emerging Technologies for Diabetes Care. DTT. 2018; 20 (S 2): S2.78-S2.84.

73. Lawton J., Blackburn M., Rankin D., Allen J., Campbell F, et al. Research: Educational and Psychlogical Aspects The impact of using a closed-loop system on food choices: a qualitative study involving adults, teenagers and parents. Diabet. Med. 2019; 36; 753-760. DOI: 10.1111/dme 13887.

74. Bekiari E., Kitsios K., Thabit H., Tauschmann M., et al. Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis. BMJ. 2018; 361: k1310. [Electronic resource] URL: http://dx.doi.org/10.1136/bmj.k1310. Accessed: 03.07.2019.

75. Rege N. K., Wickramasinghe N. P., Tustan A. N., Phillips N. F.B., Yee V. C., Ismail-Beigi F., Weiss M. A. Structure-Based Stabilization of Insulin as a Therapeutic Protein Assembly via Enhanced Aromatic-Aromatic Interactions. J Biol.Chem. 2018; 293: [Electronic resource] URL: http://www.jbc.org/content/293/28/10895. Accessed: 03.07.2019.

76. Zaykov A. N., Mayer J. P., DiMarchi R. D. Pursuit of a perfect insulin. Nature Rev. Drug Discovery. 2016; 15: 425-439.

77. Mikiewicz D., Bierczynska-Krzysik A., Sobolewska A., Stadnik D., Bogiel M., et al. Soluble Insulin Analogs Combining Rapid and Long-acting Hypoglycemic Properties – From an Efficient E. coli Expression System to a Pharmaceutical Formulation. PLoS One. 2017; 12 (3): e0172600. [Electronic resource] URL: https://journals.plos.org/ plosone/article?id=10.1371/journal.pone.0172600. Accessed: 03.07.2019. DOI: 10.1371/journal.pone.0172600.

78. Patent WO 2012/048856 A1. Proinsulin with helper sequence. Ponomarenko S., Hermann S., Eckert K. Applicant GlucoMetrix AG. Priority Date: 12.10.2010; International Filling: 11.10.2011 PCT/ EP2011/005090.

79. Hwang H.G, Kim K.-J., Lee S.-H., Kim C.-K., et al. Recombinant glargine insulin production process using Escherichia coli. JMB. 2016; 10: 1781-1789.

80. Sreenivas S., Krishnaiah S. M., Govindappa N., Basavaragu Y., et al. Enhancement in production of recombinant two-chain insulin glargine by over-expression of Kex2 protease in Pichia pastoris. Appl. Microbiol. Biotechn. 2015; 99(1): 327-336. [Electronic resource] URL: DOI 10.1007/s 00253-014-6052-5. Accessed: 03.07.2019.

81. High-throughput process development and scale-up of an intermediate purification step for recombinant insulin. GE Healthcare Life Sciences. [Electronic resource] URL: http://www. processdevelopmentforum.com/articles/high-throughput-processdevelopment-and-scale-up-of-an-intermediate-purification-step-forrecombinant-insulin/. Accessed: 03.07.2019.

82. Kim C.-K., Lee S.-B., Son Y.-J. Large-Scale Refolding and Ezyme Reaction of Human Preproinuslin for Production of Human Insulin. J Microbiol Biotechnol. 2015; 25 (10): 1742-1750. Doi: http:// dx.doi.org/10.4014/jmb.1504.04062.

83. Chen Y., Wang Q., et al. Improving the refolding efficiency for proinsulin aspart inclusion body with optimized buffer compositions. Protein Expression and Purification. 2016; 122: 1-7.

84. Gusarov D., Nekipelova V., Gusarova V., Lasman V., Bairamashvili D. Displacement effect during HPLC preparative purification of human insulin. J Chromatogr Analyt Technol Biomed Life Sci. 2009; 87 (7): 1216-1220.

85. Nanev C., Petrov K. P. Steering a crystallization process to reduce crystal polydispersity; case study of insulin crystallization. Journal of Crystal Growth. 2017; 480: 164-169.

86. Rege N. K., Weiss M. A., Phillips N. F.B. Development of Glucose-Responsive “Smart” Insulin Systems. Curr Opin Endocrinol Diabetes Obes. 2017; 24 (4): 267-278. DOI: 10.1097/MED.

87. Bally L., Thabit H., Kojzar H., Mader J. K., et al. Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomized, crossover study. Lanzet Diabetes Endocrin. 2017; 5: 261-270.

88. Thueer T., Birkhaeuer L., Reilly D. Development of an advanced injection time model for an autoinjector. Med. Devices:Evid. Research. 2018; 11: 215-224.

89. Lange J., Urbanek L., Burren S. Development of devices for selfinjection: using tribological analysis to optimize injection force. Med. Devices:Evid. Research. 2016; 9: 93-103.

90. Dadlani V., Pinsker, J.E., Dassau E., C. Kudva, Y. C. Advances in Closed-Loop Insulin Delivery Systems in Patients with Type 1 Diabetes. Current Diabetes Reports. 2018; 18 (10): [Electronic resource] URL: 18. 10.1007/s11892-018-1051-z. Accessed: 03.07.2019.

91. Gedawy A., Martinez J., Al-Salami H., Dass C. R. Oral insulin delivery: existing barriers and current counter-strategies. JPP. 2017; 70: 197-213. DOI: 10.1111/jphp.12852.

92. Ponomarenko S. V., Chshankin M. A. Impact of economic and medico-social factors on accessibility of insulin therapy for patients with diabetes mellitus in the CIS countries. Russian Journal of Biopharmaceuticals. 2018; 10 (6): P. 3-11.


For citation:


Ponomarenko S.V. Availability and Pharmacoeconomics of Insulin Therapy in Countries with the Largest Number of Diabetics. FARMAKOEKONOMIKA. Modern Pharmacoeconomic and Pharmacoepidemiology. 2019;12(3):178-190. https://doi.org/10.17749/2070-4909.2019.12.3.178-190

Views: 267


ISSN 2070-4909 (Print)
ISSN 2070-4933 (Online)