Skip to main content
SpringerLink
Log in

Systematic Review of the Economic Evaluation of Sodium–Glucose Cotransporter-2 Inhibitors Used as Treatment in Patients with Heart Failure

  • Systematic Review
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background

Sodium–glucose cotransporter-2 (SGLT2) inhibitors have been recently used as therapeutic agents for type 2 diabetes mellitus. Recent clinical trials have shown that they are beneficial for reducing the risk of cardiovascular mortality and hospitalization in patients with heart failure (HF). A comprehensive review regarding the cost-effectiveness of different SGLT2 inhibitors for HF treatment may be necessary to help clinicians and decision-makers select the most cost-effective HF treatment option.

Objective

This study conducted a systematic review of economic evaluation studies of SGLT2 inhibitors for the treatment of patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF).

Method

We searched PubMed, Cochrane, Embase, and EBSCOhost to identify published economic evaluation studies on SGLT2 inhibitors for HF treatment until May 2023. Studies on the economic evaluation of SGLT2 inhibitors in the treatment of HF were included. We extracted information such as country, population, intervention, type of model, health status, and conclusion of cost-effectiveness.

Result

Of the 410 studies, 27 were finally selected. All economic evaluation studies used the Markov model, and commonly included health status as stable HF, hospitalization due to HF, and death. All dapagliflozin studies focused on patients with HFrEF (n = 13), and dapagliflozin was cost-effective in 14 countries, but not in the Philippines. All empagliflozin studies focused on the patients with HFrEF also showed the cost-effectiveness of empagliflozin (n = 11). However, empagliflozin use in patients with HFpEF was determined to be cost-effective in studies in Finland, China, and Australia studies but not in studies in Thailand and the USA.

Conclusions

Most of the studies reported the cost-effectiveness of dapagliflozin and empagliflozin in patients with HFrEF. However, the cost-effectiveness of empagliflozin differed from country to country regarding patients with HFpEF. We suggest that further economic evaluation of SGLT2 inhibitors should focus on patients with HFpEF in more countries.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Chen Z, Li G. Sodium–glucose co-transporter 2 inhibitors compared with sulfonylureas in patients with type 2 diabetes inadequately controlled on metformin: a meta-analysis of randomized controlled trials. Clin Drug Investig. 2019;39(6):521–31.

    CAS  PubMed  Google Scholar 

  2. American Diabetes Association Professional Practice C. Addendum. 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2022. Diabetes Care 2022;45(Suppl. 1):S144–S174. Diabetes Care. 2022;45(9):2178–81.

  3. American DA. Introduction: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S1–2.

    Google Scholar 

  4. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347–57.

    CAS  PubMed  Google Scholar 

  5. Correale M, Mazzeo P, Tricarico L, Croella F, Fortunato M, Magnesa M, et al. Pharmacological anti-remodelling effects of disease-modifying drugs in heart failure with reduced ejection fraction. Clin Drug Investig. 2022;42(7):567–79.

    CAS  PubMed  Google Scholar 

  6. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.

    CAS  PubMed  Google Scholar 

  7. Solomon SD, de Boer RA, DeMets D, Hernandez AF, Inzucchi SE, Kosiborod MN, et al. Dapagliflozin in heart failure with preserved and mildly reduced ejection fraction: rationale and design of the DELIVER trial. Eur J Heart Fail. 2021;23(7):1217–25.

    CAS  PubMed  Google Scholar 

  8. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008.

    CAS  PubMed  Google Scholar 

  9. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413–24.

    CAS  PubMed  Google Scholar 

  10. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451–61.

    CAS  PubMed  Google Scholar 

  11. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–57.

    CAS  PubMed  Google Scholar 

  12. Curtis JP, Sokol SI, Wang Y, Rathore SS, Ko DT, Jadbabaie F, et al. The association of left ventricular ejection fraction, mortality, and cause of death in stable outpatients with heart failure. J Am Coll Cardiol. 2003;42(4):736–42.

    PubMed  Google Scholar 

  13. Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2021;384(2):117–28.

    CAS  PubMed  Google Scholar 

  14. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–726.

    CAS  PubMed  Google Scholar 

  15. Elserafy AS, Reda A, Farag E, Mostafa T, Farag N, Elbahry A, et al. Egyptian atherosclerosis and vascular biology association consensus on the use of sodium glucose cotransporter-2 inhibitors in heart failure with reduced ejection fraction. Clin Drug Investig. 2021;41(12):1027–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Association AH. 2022 AHA/ACC/HFSA guideline for the management of heart failure. J Card Fail. 2022;28(5):e1–167.

    Google Scholar 

  17. Tsutsui H, Ide T, Ito H, Kihara Y, Kinugawa K, Kinugawa S, et al. JCS/JHFS 2021 guideline focused update on diagnosis and treatment of acute and chronic heart failure. Circ J. 2021;85(12):2252–91.

    CAS  PubMed  Google Scholar 

  18. failure TKsoh. KSHF 2022 guideline for the management of heart failure. 2022 ed. Seoul: The Korean Society of Heart Failure; 2022.

  19. Piette JD, Heisler M, Krein S, Kerr EA. The role of patient-physician trust in moderating medication nonadherence due to cost pressures. Arch Intern Med. 2005;165(15):1749–55.

    PubMed  Google Scholar 

  20. Heisler M, Wagner TH, Piette JD. Clinician identification of chronically ill patients who have problems paying for prescription medications. Am J Med. 2004;116(11):753–8.

    PubMed  Google Scholar 

  21. Piette JD, Heisler M, Horne R, Caleb AG. A conceptually based approach to understanding chronically ill patients’ responses to medication cost pressures. Soc Sci Med. 2006;62(4):846–57.

    PubMed  Google Scholar 

  22. Wahlster P, Scahill S, Lu CY, Babar Z-U-D. Barriers to access and use of high cost medicines: a review. Health Policy Technol. 2015;4(3):191–214.

    Google Scholar 

  23. Taylor C, Jan S. Economic evaluation of medicines. Aust Prescr. 2017;40(2):76–8.

    PubMed  PubMed Central  Google Scholar 

  24. Hoyle M. Future drug prices and cost-effectiveness analyses. Pharmacoeconomics. 2008;26(7):589–602.

    CAS  PubMed  Google Scholar 

  25. Platz E, Jhund PS, Claggett BL, Pfeffer MA, Swedberg K, Granger CB, et al. Prevalence and prognostic importance of precipitating factors leading to heart failure hospitalization: recurrent hospitalizations and mortality. Eur J Heart Fail. 2018;20(2):295–303.

    PubMed  Google Scholar 

  26. Yoshida Y, Cheng X, Shao H, Fonseca VA, Shi L. A systematic review of cost-effectiveness of sodium–glucose cotransporter inhibitors for type 2 diabetes. Curr Diabetes Rep. 2020;20(4):12.

    Google Scholar 

  27. Hong D, Si L, Jiang M, Shao H, Ming WK, Zhao Y, et al. Cost effectiveness of sodium–glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors: a systematic review. Pharmacoeconomics. 2019;37(6):777–818.

    PubMed  Google Scholar 

  28. Wu M, Qin S, Wang L, Tan C, Peng Y, Zeng X, et al. Economic evaluation of dapagliflozin in the treatment of patients with heart failure: a systematic review. Front Pharmacol. 2022;13: 860109.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;29(372): n71.

    Google Scholar 

  30. Ofman JJ, Sullivan SD, Neumann PJ, Chiou CF, Henning JM, Wade SW, et al. Examining the value and quality of health economic analyses: implications of utilizing the QHES. J Manag Care Pharm. 2003;9(1):53–61.

    PubMed  Google Scholar 

  31. Jiang Y, Zheng R, Sang H. Cost-effectiveness of adding SGLT2 inhibitors to standard treatment for heart failure with reduced ejection fraction patients in China. Front Pharmacol. 2021;12:733681.

  32. Nguyen BN, Mital S, Bugden S, Nguyen HV. Cost-effectiveness of dapagliflozin and empagliflozin for treatment of heart failure with reduced ejection fraction. Int J Cardiol. 2023;1(376):83–9.

    Google Scholar 

  33. Cohen LP, Isaza N, Hernandez I, Lewis GD, Ho JE, Fonarow GC, et al. Cost-effectiveness of sodium-glucose cotransporter-2 inhibitors for the treatment of heart failure with preserved ejection fraction. JAMA Cardiol. 20231;8(5):419–28.

  34. Abdelhamid M, Elsisi GH, Seyam A, Shafie A, Kirollos M, Emad S, et al. Dapagliflozin cost-effectiveness analysis in heart failure patients in Egypt. J Med Econ. 2022;25(1):450–6.

    PubMed  Google Scholar 

  35. Gil-Rojas Y, Lasalvia P, García Á. Cost-utility of dapagliflozin plus standard treatment compared to standard treatment for the management of heart failure with reduced ejection fraction in Colombia. Expert Rev Pharmacoecon Outcomes Res. 2022;22(4):655–63.

    PubMed  Google Scholar 

  36. Isaza N, Calvachi P, Raber I, Liu CL, Bellows BK, Hernandez I, et al. Cost-effectiveness of dapagliflozin for the treatment of heart failure with reduced ejection fraction. JAMA Netw Open. 2021;4(7): e2114501.

    PubMed  PubMed Central  Google Scholar 

  37. Krittayaphong R, Permsuwan U. Cost-utility analysis of add-on dapagliflozin treatment in heart failure with reduced ejection fraction. Int J Cardiol. 2021;322:183–90.

    PubMed  Google Scholar 

  38. Liao CT, Yang CT, Toh HS, Chang WT, Chang HY, Kuo FH, et al. Cost-effectiveness evaluation of add-on dapagliflozin for heart failure with reduced ejection fraction from perspective of healthcare systems in Asia-Pacific region. Cardiovasc Diabetol. 2021;20(1):204.

  39. McEwan P, Darlington O, McMurray JJV, Jhund PS, Docherty KF, Böhm M, et al. Cost-effectiveness of dapagliflozin as a treatment for heart failure with reduced ejection fraction: a multinational health-economic analysis of DAPA-HF. Eur J. 2020;22(11):2147–56.

    Google Scholar 

  40. Mendoza VL, Tumanan-Mendoza BA, Punzalan FER. Cost-utility analysis of add-on dapagliflozin in heart failure with reduced ejection fraction in the Philippines. ESC. 2021;8(6):5132–41.

    Google Scholar 

  41. Miller RJH, Chew DS, Qin L, Fine NM, Chen J, McMurray JJV, et al. Cost-effectiveness of immediate initiation of dapagliflozin in patients with a history of heart failure. Eur J Heart Fail. 2023;25(2):238–47.

    PubMed  Google Scholar 

  42. Parizo JT, Goldhaber-Fiebert JD, Salomon JA, Khush KK, Spertus JA, Heidenreich PA, et al. Cost-effectiveness of dapagliflozin for treatment of patients with heart failure with reduced ejection fraction. JAMA Cardiol. 2021;6(8):926–35.

    PubMed  Google Scholar 

  43. Savira F, Wang BH, Kompa AR, Ademi Z, Owen AJ, Zoungas S, et al. Cost-effectiveness of dapagliflozin in chronic heart failure: an analysis from the Australian healthcare perspective. Eur J Prev Cardiol. 2021;28(9):975–82.

    PubMed  Google Scholar 

  44. Yao Y, Zhang R, An T, Zhao X, Zhang J. Cost-effectiveness of adding dapagliflozin to standard treatment for heart failure with reduced ejection fraction patients in China. ESC. 2020;7(6):3582–92.

    Google Scholar 

  45. Hallinen T, Kivela S, Soini E, Harjola VP, Pesonen M. Cost-effectiveness of empagliflozin in combination with standard care versus standard care only in the treatment of heart failure patients in Finland. ClinicoEcono Outcomes Res. 2023;15:1–13.

    Google Scholar 

  46. Jiang Y, Xie J. Cost-effectiveness of adding empagliflozin to the standard therapy for heart failure with preserved ejection fraction from the perspective of healthcare systems in China. Front Cardiovasc Med. 2022;9:946399.

  47. Krittayaphong R, Permsuwan U. Cost-utility analysis of combination empagliflozin and standard treatment versus standard treatment alone in thai heart failure patients with reduced or preserved ejection fraction. Am J Cardiovasc Drugs. 2022;22(5):577–90.

    CAS  PubMed  Google Scholar 

  48. Liao CT, Yang CT, Kuo FH, Lee MC, Chang WT, Tang HJ, et al. Cost-effectiveness evaluation of add-on empagliflozin in patients with heart failure and a reduced ejection fraction from the healthcare system’s perspective in the Asia-Pacific Region. Front Cardiovasc Med. 2021;8: 750381.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Lin X, Lin M, Liu M, Huang W, Nie X, Chen Z, et al. Cost-effectiveness of empagliflozin as a treatment for heart failure with reduced ejection fraction: an analysis from the Chinese healthcare perspective. J Thorac Dis. 2022;14(5):1588–97.

    PubMed  PubMed Central  Google Scholar 

  50. Lou Y, Hu T, Huang J. Cost-effectiveness of adding empagliflozin to standard treatment for heart failure with preserved ejection fraction patients in China. Am J Cardiovasc Drugs. 2023;23(1):47–57.

  51. Sang H, Wan Y, Ma Z, Zhang S, Zhao Q. Cost-effectiveness of empagliflozin for the treatment of heart failure with reduced ejection fraction in China. Front Cardiovasc Med. 2022;9:1022020.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Tafazzoli A, Reifsnider OS, Bellanca L, Ishak J, Carrasco M, Rakonczai P, et al. A European multinational cost-effectiveness analysis of empagliflozin in heart failure with reduced ejection fraction. Eur J Health Econ. 2022 Dec 4.

  53. Tang Y, Sang H. Cost-utility analysis of empagliflozin in heart failure patients with reduced and preserved ejection fraction in China. Front Pharmacol. 2022;13:1030642.

  54. Tsutsui H, Sakamaki H, Momomura SI, Sakata Y, Kotobuki Y, Linden S, et al. Cost-effectiveness analysis of empagliflozin in patients with heart failure with reduced ejection fraction in Japan based on the EMPEROR-reduced trial. J Cardiol. 2023;81(6):522–30.

    PubMed  Google Scholar 

  55. Varghese L, Lin W, Linden S, Lum AL, Sim D. Cost-effectiveness of empagliflozin on top of standard of care for heart failure with reduced ejection fraction in Singapore. Value Health Reg Issues. 2023;34:108–17.

    PubMed  Google Scholar 

  56. Zheng J, Parizo JT, Spertus JA, Heidenreich PA, Sandhu AT. Cost-effectiveness of empagliflozin in patients with heart failure with preserved ejection fraction. JAMA Intern Med. 2022;182(12):1278–88.

    CAS  PubMed  Google Scholar 

  57. Zhou J, Liew D, Kaye DM, Zoungas S, Stub D. Cost-effectiveness of empagliflozin in patients with heart failure and preserved ejection fraction. Circ Cardiovasc Qual Outcomes. 2022;15(10): e008638.

    PubMed  Google Scholar 

  58. Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. Publication bias in clinical research. Lancet. 1991;337(8746):867–72.

    CAS  PubMed  Google Scholar 

  59. Reifsnider OS, Kansal AR, Gandhi PK, Cragin L, Brand SB, Pfarr E, et al. Cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or standard of care in patients with type 2 diabetes and established cardiovascular disease. BMJ Open Diabetes Res Care. 2021;9(1).

  60. Coles AH, Fisher K, Darling C, Yarzebski J, McManus DD, Gore JM, et al. Long-term survival for patients with acute decompensated heart failure according to ejection fraction findings. Am J Cardiol. 2014;114(6):862–8.

    PubMed  PubMed Central  Google Scholar 

  61. Liu XQ, He LS, Huang JQ, Xiong LJ, Xia C, Lao HY. Cost-effectiveness analyses of sacubitril-valsartan for heart failure. Heart Fail Rev. 2021;26(5):1119–30.

    PubMed  Google Scholar 

  62. Arbel R, Aboalhasan E, Hammerman A, Azuri J. Dapagliflozin vs. sacubitril-valsartan for prevention of heart failure events in non-diabetic patients with reduced ejection fraction: a cost per outcome analysis. Eur J Prev Cardiol. 2021;28(15):1665–9.

    PubMed  Google Scholar 

  63. Hammerman A, Azuri J, Aboalhasan E, Arbel R. Dapagliflozin versus sacubitril-valsartan to improve outcomes of patients with reduced ejection fraction and diabetes mellitus. Am J Cardiovasc Drugs. 2022;22(3):325–31.

    CAS  PubMed  Google Scholar 

  64. Xie F, Zhou T. Industry sponsorship bias in cost effectiveness analysis: registry based analysis. BMJ. 2022;22(377): e069573.

    Google Scholar 

Download references

Acknowledgements

We would like to thank Editage (http://www.editage.co.kr) for English-language editing and reviewing of this manuscript.

Author information

Authors and Affiliations

  1. College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea

    Kyungae Nam, Daniel Sung-Ho Cho, Hyunji Kim, Byungjin Kwon, Yebin Yoon & Sun-Kyeong Park

  2. Health Outcomes Division, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA

    Chanhyun Park

  3. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea

    Eui-Soon Kim

  4. Division of Cardiology, Department of Internal Medicine, Seoul St. Mary’s Hospital, Catholic Research Institute for Intractable Cardiovascular Disease, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Jong-Chan Youn

Authors
  1. Kyungae Nam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Sung-Ho Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyunji Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Byungjin Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yebin Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chanhyun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eui-Soon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jong-Chan Youn
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sun-Kyeong Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sun-Kyeong Park.

Ethics declarations

Funding

This work was supported by the Research Fund, 2020 of The Catholic University of Korea. However, the sponsor had no role in the study design; collection, analysis, and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication.

Conflict of interest

All authors have no conflict of interest to declare.

Ethics approval, consent to participate and consent for publication

Not applicable.

Availability of data and material

All articles included in the study can be found and accessed in their respective journals according to their bibliographic information.

Code availability

Not applicable.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 620 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nam, K., Cho, D.SH., Kim, H. et al. Systematic Review of the Economic Evaluation of Sodium–Glucose Cotransporter-2 Inhibitors Used as Treatment in Patients with Heart Failure. Clin Drug Investig 43, 463–474 (2023). https://doi.org/10.1007/s40261-023-01283-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40261-023-01283-6

Search

Navigation