DOI QR코드

DOI QR Code

Use of SGLT2 inhibitor/metformin fixed dose combination in Korea

SGLT2 저해제/metformin 고정용량복합제의 국내 사용 현황

  • Received : 2022.01.12
  • Accepted : 2022.03.12
  • Published : 2022.03.31

Abstract

Background: The use of combination therapy and fixed-dose combination therapy is increasing for the treatment of type 2 diabetes. Sodium glucose cotransporter-2 inhibitor (SGLT2i) is a drug class used in combination with metformin. Methods: Type 2 diabetes patients on SGLT2i/metformin combination therapy were extracted from the 2019 Health Insurance Review & Assessment Service-National Patients Sample. On July 1, 2019, SGLT2i and metformin fixed-dose combination (SGLT2i/metformin FDC) and two-pill combination (TPC) groups were identified, and a chi-square test and multiple logistic regression were performed. Results: Of total 2,992 patients, 1,077 (36%) were prescribed SGLT2i/metformin FDC and 1,915 (64%) were prescribed TPC. We found that the most common comorbidities were in the order of dyslipidemia, gastrointestinal disease, and hypertension. Multiple logistic regression analysis showed that the use of SGLT2i/metformin FDC was lower than TPC in patients with diabetic neuropathy (OR=0.76, p=0.008). Clinic (OR=2.09, p<0.001) and general hospital (OR=1.40, p=0.019) showed higher tendency to prescribe SGLT2i/metformin FDC compared to tertiary hospital. The tendency of prescribing SGLT2i/metformin FDC was lower in Kyeonggi (OR=0.79, p=0.037), Gyeongsang (OR=0.77, p=0.025) and Chungcheong (OR=0.68, p=0.007) than Seoul. Conclusion: Factors related to the use of SGLT2i/metformin FDC in patients with type 2 diabetes were complication, medical institution and region. The tendency to prescribe SGLT2i/metformin FDC was relatively higher in clinics than in tertiary general hospitals and in Seoul than in other regions.

Keywords

References

  1. Korean Statistical Infromation Service. Diabetes: ≥30 years 2021. Available from https://kosis.kr/statHtml/statHtml.do?orgId=177&tblId=DT_11702_N102&conn_path=I2&language=en. Accessed September 23, 2021.
  2. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27(5):1047-53. https://doi.org/10.2337/diacare.27.5.1047
  3. Danaei G, Finucane MM, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 2011;378(9785):31-40. https://doi.org/10.1016/S0140-6736(11)60679-X
  4. Korean diabetes association. Clinical practice guidelines for diabetes 2021. Available from https://www.diabetes.or.kr/pro/publish/guide.php?mode=list. Accessed January 07, 2022.
  5. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of medical care in diabetes-2021. Diabetes care 2021;44(Suppl 1):S111-S124. https://doi.org/10.2337/dc21-S009
  6. Ko SH, Kim DJ, Park JH, et al. Trends of antidiabetic drug use in adult type 2 diabetes in Korea in 2002-2013: Nationwide population-based cohort study. Medicine (Baltimore) 2016;95(27):e4018. https://doi.org/10.1097/md.0000000000004018
  7. Fujita Y, Inagaki N. Renal sodium glucose cotransporter 2 inhibitors as a novel therapeutic approach to treatment of type 2 diabetes: Clinical data and mechanism of action. J Diabetes Investig 2014;5(3):265-75. https://doi.org/10.1111/jdi.12214
  8. Ministry of Food and Drug Safety. Medicines integrated information system. Available from https://nedrug.mfds.go.kr/searchDrug. Accessed January 07, 2022.
  9. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of medical care in diabetes-2019. Diabetes care 2019;42(Suppl. 1):S90-S102. https://doi.org/10.2337/dc19-S009
  10. Huang ES, Karter AJ, Danielson KK, Warton EM, Ahmed AT. The association between the number of prescription medications and incident falls in a multi-ethnic population of adult type-2 diabetes patients: the diabetes and aging study. J Gen Intern Med 2010;25(2):141-6. https://doi.org/10.1007/s11606-009-1179-2
  11. Bluher M, Kurz I, Dannenmaier S, Dworak M. Pill burden in patients with type 2 diabetes in Germany: Subanalysis from the prospective, noninterventional PROVIL study. Clin Diabetes 2015;33(2):55-61. https://doi.org/10.2337/diaclin.33.2.55
  12. Donnan PT, MacDonald TM, Morris AD. Adherence to prescribed oral hypoglycaemic medication in a population of patients with Type 2 diabetes: a retrospective cohort study. Diabet Med 2002;19(4):279-84. https://doi.org/10.1046/j.1464-5491.2002.00689.x
  13. Baumgartner A, Drame K, Geutjens S, Airaksinen M. Does the polypill improve patient adherence compared to its individual formulations? A systematic review. Pharmaceutics 2020;12(2):190. https://doi.org/10.3390/pharmaceutics12020190
  14. Bell DS. Combine and conquer: advantages and disadvantages of fixed-dose combination therapy. Diabetes Obes Metab 2013;15(4):291-300. https://doi.org/10.1111/dom.12015
  15. Zonszein J, Groop PH. Strategies for Diabetes Management: Using Newer Oral Combination Therapies Early in the Disease. Diabetes Ther 2016;7(4):621-39. https://doi.org/10.1007/s13300-016-0208-5
  16. Lingvay I, Nadine Beetz N, Sennewald R, et al. Triple fixed-dose combination empagliflozin, linagliptin, and metformin for patients with type 2 diabetes. Postgrad Med 2020;132(4):337-45. https://doi.org/10.1080/00325481.2020.1750228
  17. Han S, Iglay K, Davies MJ, Zhang Q, Radican L. Glycemic effectiveness and medication adherence with fixed-dose combination or coadministered dual therapy of antihyperglycemic regimens: a meta-analysis. Curr Med Res Opin 2012;28(6):969-77. https://doi.org/10.1185/03007995.2012.684045
  18. Blonde L, Wogen J, Kreilick C, Seymour AA. Greater reductions in A1C in type 2 diabetic patients new to therapy with glyburide/metformin tablets as compared to glyburide co-administered with metformin. Diabetes Obes Metab 2003;5(6):424-31. https://doi.org/10.1046/j.1463-1326.2003.00297.x
  19. HU J, Zou P, Zhang S, Zhou M, Tan X. Empagliflozin/metformin fixed-dose combination: a review in patients with type 2 diabetes. Expert Opin Pharmacother 2016;17(18):2471-7. https://doi.org/10.1080/14656566.2016.1258062
  20. Benford M, Milligan G, Pike J, Anderson P, Piercy J, Fermer S. Fixed-dose combination antidiabetic therapy: real-world factors associated with prescribing choices and relationship with patient satisfaction and compliance. Adv Ther 2012;29(1):26-40. https://doi.org/10.1007/s12325-011-0096-z
  21. Kim J, Park S, Kim H, Je NK. National trends in metformin-based combination therapy of oral hypoglycaemic agents for type 2 diabetes mellitus. Eur J Clin Pharmacol 2019;75(12):1723-30. https://doi.org/10.1007/s00228-019-02751-9
  22. Kaur KK, Allahbadia G, Singh M. Role of combination therapy with SGLT2 Inhibitor with metformin as initial treatment for type2 diabetes-advantages of oral fixed drug pill like empagliflozin/metformin in patients with cardiovascular and renal risk-A short communication. Arch Endocrinol Metab 2019;2(1):15-9.
  23. Health Insurance Review and Assessment Service. Healthcare Bigdata Hub. Available from https://opendata.hira.or.kr/home.do. Accessed September 24, 2021.
  24. Schipf S, Werner A, Tamayo T, et al. Regional differences in the prevalence of known Type 2 diabetes mellitus in 45-74 years old individuals: results from six population-based studies in Germany (DIAB-CORE Consortium). Diabet Med 2012;29(7):e88-95. https://doi.org/10.1111/j.1464-5491.2012.03578.x
  25. Valov V, Doneva M, Borisova AM, et al. Regional differences in diabetic patients' pharmacotherapy in Bulgaria. Eur Rev Med Pharmacol Sci 2014;18(10):1499-506.
  26. Oh JA, Lee GM, Chung SY, Cho YS, Lee HJ. Utilization trends of proton pump inhibitors in South Korea: Analysis using 2016-2020 Healthcare Bigdata Hub by Health Insurance Review and Assessment Service. Yakhak Hoeji 2021;65(4):276-83. https://doi.org/10.17480/psk.2021.65.4.276
  27. Health Insurance Review and Assessment Service. 2019 Drug reimbursement adequacy evaluation result. Available from https://www.hira.or.kr/cms/open/04/04/12/2020_9.pdf. Accessed October 8, 2021.
  28. Korean Statistical Infromation Service. Number of doctors employed in medical institutions per 1,000 population. Available from https://kosis.kr/statHtml/statHtml.do?orgId=101&tblId=DT_1YL20981&conn_path=I2. Accessed October 8, 2021.
  29. Frias JP. Fixed-dose combination of ertugliflozin and metformin hydrochloride for the treatment of type 2 diabetes. Expert Rev Endocrinol Metab 2019;14(2):75-83. https://doi.org/10.1080/17446651.2019.1571908
  30. Hutchins V, Zhang B, Fleurence RL, Krishnarajah G, Graham J. A systematic review of adherence, treatment satisfaction and costs, in fixed-dose combination regimens in type 2 diabetes. Curr Med Res Opin 2011;27(6):1157-68. https://doi.org/10.1185/03007995.2011.570745
  31. Korean Pharmaceutical Information center. Available from https://www.health.kr/. Accessed December 25, 2021.
  32. Park JH, Lee BK, Kim JY, Gwak HS. Comparisons of adherence, efficacy and price between sitagliptin/metformin fixed-dose combination tablets and concomitant administration of sitagliptin and metformin in type 2 diabetes mellitus patients. Korean J Clin Pharm 2014;24(3):193-8.
  33. Bohm AK, Schneider U, Aberle J, Stargardt T. Regimen simplification and medication adherence: Fixed-dose versus loose-dose combination therapy for type 2 diabetes. PLoS One 2021;16(5):e0250993. https://doi.org/10.1371/journal.pone.0250993
  34. Moriarty F, Bennett K, Fahey T. Fixed-dose combination antihypertensives and risk of medication errors. Heart 2019;105(3):204-9. https://doi.org/10.1136/heartjnl-2018-313492