A Systematic Review: Cost-Effectiveness of SGLT2 Inhibitors versus DPP-4 Inhibitors as Add-on to Metformin
Downloads
Background: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) are two second-line therapy alternatives for T2DM patients inadequately controlled with metformin. Objective: This study aimed to systematically review the cost-effectiveness of combining metformin+SGLT2i vs metformin+DPP-4i for T2DM treatment. Methods: A systematic search was conducted in PubMed, Scopus, and ScienceDirect for articles published between 2015-2025, using predefined keywords and following the PRISMA and PICOS frameworks (P: T2DM patients uncontrolled on metformin monotherapy; I: Metformin+SGLT2i therapy; C: Metformin+DPP-4i therapy; O: Cost, clinical outcomes (HbA1c% reduction), Incremental Cost-Effectiveness Ratio (ICER) values, Quality Adjusted Life Years (QALY); S: Study with cost-effectiveness analysis design). Additional studies were identified through reference screening. Eligible articles were independently reviewed and assessed for reporting quality using the CHEERS-2022 standards. Results: Five studies met the inclusion criteria. Considerable heterogeneity was observed with mean patient ages ranging from 55-61 years old and baseline HbA1c levels from 7.9%-9.4%. The studies were conducted in the US, UK, Mexico, and Greece, all funded by the pharmaceutical industry, and used economic models. Despite these differences, all studies consistently demonstrated that combining metformin+SGLT2i was more cost-effective than metformin+DPP-4i. SGLT2i improved the quality of life by 0.032–0.04 QALYs, reduced hypoglycemia, and provided additional benefits for patients with cardiovascular risk, although it was associated with higher initial costs. Conclusion: This review showed that the combination of metformin+SGLT2i was more cost-efficient and effective in managing T2DM than the combination of metformin+DPP-4i.
American Diabetes Association. (2025). Standards of Care in Diabetes 2025. The Journal of Clinical and Applied Research and Education, 48(Supplement 1). Virginia: American Diabetes Association.
Andayani, T. M. (2013). Farmakoterapi Prinsip dan Metodelogi. Yogyakarta: Bursa Ilmu.
Chakravarty, A., Rastogi, M., Dhankhar, P., & Bell, K. F. (2018). Comparison of Costs and Outcomes of Dapagliflozin with Other Glucose-Lowering Therapy Classes Added to Metformin Using a Short-Term Cost-Effectiveness Model in the US Setting. Journal of Medical Economics; 21; 497–509. doi: 10.1080/13696998.2018.1434182.
Charokopou, M., McEwan, P., Lister, S., Callan, L., Bergenheim, K., Tolley, K., Postema, R., Townsend, R., & Roudaut, M. (2015). Cost-Effectiveness of Dapagliflozin Versus DPP-4 Inhibitors as an Add-On to Metformin in the Treatment of Type 2 Diabetes Mellitus from a UK Healthcare System Perspective. BMC Health Services Research; 15; 496. doi: 10.1186/s12913-015-1139-y.
Cummins, E., Scott, N., & Rothnie, K. (2012). Dapagliflozin for the Treatment of Type 2 Diabetes. Scotland: Aberdeen HTA Group.
Hadjadj, S., Rosenstock, J., Meinicke, T., Woerle, H. J., & Broedl, U. C. (2016). Initial Combination of Empagliflozin and Metformin in Patients with Type 2 Diabetes. Diabetes Care; 39; 1718–1728.
Hsia, D. S., Grove, O., & Cefalu, W. T. (2017). An Update on SGLT2 Inhibitors for the Treatment of Diabetes Mellitus. Current Opinion in Endocrinology, Diabetes and Obesity; 24; 73–79. doi: 10.1097/MED. 0000000000000311
International Diabetes Federation. (2024). September 30). IDF Diabetes Atlas. Brussels: IDF Diabetes Atlas.
Kemenkes. (2013). Pedoman Penerapan Kajian Farmakoekonomi. Jakarta: Kementerian Kesehatan RI.
Lopez, J. M. S., Macomson, B., Ektare, V., Patel, D., & Botteman, M. (2015). Evaluating Drug Cost per Response with SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus. American Health & Drug Benefits; 8; 309–318.
Müller, W. D., Kellere, M., Cypryk, K., & Skripova, D. (2018). Efficacy and Safety of Dapagliflozin or Dapagliflozin Plussaxagliptin Versus Glimepiride as Add-On to Metformin Inpatients with Type 2 Diabetes. Diabetes, Obesity and Metabolism; 20; 2598–2607. doi: 10.1111/dom.13437.
Neslusan, C., Teschemaker, A., Johansen, P., Willis, M., Valencia-Mendoza, A., & Puig, A. (2015). Cost-Effectiveness of Canagliflozin versus Sitagliptin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus in Mexico. Value in Health Regional Issues; 8; 8–19. doi: 10.1016/j.vhri.2015.01.002.
Page, M., McKenzie, J., Bossuyt, P., Boutron, I., Hoffmann, T., & Mulrow, C. (2021). The PRISMA 2020 statement: An Updated Guideline for Reporting Systematic Reviews. BMJ; 372; 1-9. doi: 10.1136/bmj.n71.
Peng, Z., Yang, C., Ou, H., & Kuo, S. (2022). Cost‐Effectiveness of Sodium-glucose Cotransporter-2 Inhibitors Versus Dipeptidyl Peptidase-4 Inhibitors Among Patients with Type 2 Diabetes With and Without Established Cardiovascular Diseases: A Model-based Simulation Analysis Using 10-year Real-world Data and Targeted Literature Review. Diabetes, Obesity and Metabolism; 24; 1328–1337. doi: 10.1111/dom.14708.
Reifsnider, O., Kansal, A., Pimple, P., Aponte‐Ribero, V., Brand, S., & Shetty, S. (2021). Cost‐Effectiveness Analysis of Empagliflozin Versus Sitagliptin as Second‐Line Therapy for Treatment in Patients with Type 2 Diabetes in the United States. Diabetes, Obesity and Metabolism; 23; 791–799. doi: 10.1111/dom.14268.
Rosenstock, J., Chuck, L., González-Ortiz, M., Merton, K., Craig, J., Capuano, G., & Qiu, R. (2016). Initial Combination Therapy with Canagliflozin Plus Metformin Versus Each Component as Monotherapy for Drug-Naïve Type 2 Diabetes. Diabetes Care; 39; 353–362.
Tzanetakos, C., Tentolouris, N., Kourlaba, G., & Maniadakis, N. (2016). Cost-Effectiveness of Dapagliflozin as Add-On to Metformin for the Treatment of Type 2 Diabetes Mellitus in Greece. Clinical Drug Investigation; 36; 649–659. doi: 10.1007/s40261-016-0410-2.
Yoshida, Y., Cheng, X., Shao, H., Fonseca, V. A., & Shi, L. (2020). A Systematic Review of Cost-Effectiveness of Sodium-Glucose Cotransporter Inhibitors for Type 2 Diabetes. Current Diabetes Reports; 20; 12. doi: 10.1007/s11892-020-1292-5.
Zhu, J., Zhou, Y., Li, Q., & Wang, G. (2023). Cost-Effectiveness of Newer Antidiabetic Drugs as Second-Line Treatment for Type 2 Diabetes: a Systematic Review. Advances in Therapy, 40; 4216–4235. doi: 10.1007/s12325-023-02612-z.
Copyright (c) 2025 JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
1. The copyright of this journal belongs to the Editorial Board and Journal Manager with the author's knowledge, while the moral right of the publication belong to the author.
2. The formal legal aspect of journal publication accessibility refers to the Creative Commons Attribution-Non-Commercial-Share Alike (CC BY-NC-SA), which implies that the publication can be used for non-commercial purposes in its original form.
3. Every publication (print/electronic) is open access for educational, research, and library purposes. In addition to the objectives mentioned above, the editorial board is not responsible for copyright infringement
.jpg)
