Impact of SGLT2 inhibitors on heart failure risk and kidney function in type 2 diabetic mellitus patients: A literature review

Authors

  • Chelsy Vanya Br. Meliala Faculty of Military Pharmacy, Indonesia Defense University
  • Syahrul Tuba Faculty of Military Pharmacy, Republic of Indonesia Defense University, West Java-16810, Indonesia https://orcid.org/0000-0002-3082-8891
  • Adi Priyono Faculty of Military Pharmacy, Indonesia Defense University
  • Syed Azhar Syed Sulaiman School of Pharmaceutical Sciences, Universiti Sains Malaysia
  • Budi Sumaryono Faculty of Military Pharmacy, Indonesia Defense University
  • Endah Permata Sari Faculty of Pharmacy, Muslim University of Indonesia

DOI:

https://doi.org/10.58524/app.sci.def.v4i2.1134

Keywords:

Heart Failure, Renal Failure, SGLT2i, Type 2 Diabetic

Abstract

Background: Type 2 diabetes mellitus is known to be closely associated with an increased risk of heart failure and chronic kidney disease, both of which are major causes of illness and death in diabetic patients. In recent years, sodium-glucose cotransporter-2 inhibitors (SGLT2i), which were initially developed as blood glucose-lowering drugs, have been shown to provide additional benefits beyond glycemic control, particularly in protecting the heart and kidneys.

Aims: This literature review aims to comprehensively evaluate the impact of SGLT2 inhibitor use on the risk of heart failure and renal function outcomes in patients with type 2 diabetes mellitus (T2DM).

Method: A literature search was conducted through the PubMed, Scopus, and ScienceDirect databases for publications from 2015 to 2025, including randomized controlled trials (RCTs), meta-analyses, and systematic reviews using the keywords "SGLT2 inhibitors," "heart failure," "renal outcomes," and "type 2 diabetes."

Results: from various large clinical trials and meta-analyses show that SGLT2 inhibitors consistently reduce the risk of hospitalization due to heart failure and cardiovascular death, with a hazard ratio generally below 0.80. In addition, this therapy also slows the decline in glomerular filtration rate (eGFR), thereby reducing deaths due to renal causes.

Conclusion: SGLT-2i has been shown to provide strong cardio-renal protection in patients with T2DM, especially in individuals at high risk of heart failure or chronic kidney disease, in accordance with current clinical guidelines.

References

Alrasheed, R. R., Altaf, A. F., Althurwi, A. H., Alrodan, S. F., Asiri, M. H., Alsaluli, B. A., Alsurur, M. A., Alghamdi, K. A., Alrowaithi, A. A., & Almalki, N. S. (2025c). Heart Failure Outcomes with SGLT2 Inhibitors in Adults with Type 2 Diabetes: A Systematic Review and Meta-Analysis. Medicina, 62(1), 69. https://doi.org/10.3390/medicina62010069

American Diabetes Association Professional Practice Committee. (2025). 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2025. Diabetes Care, 48(1 Suppl 1), S181–S206. https://doi.org/10.2337/dc25-S009

American Diabetes Association Professional Practice Committee. (2025). 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025. Diabetes Care, 48(Supplement_1), S207–S238. https://doi.org/10.2337/dc25-S010

Bhatt, D. L., Szarek, M., Steg, P. G., Cannon, C. P., Leiter, L. A., McGuire, D. K., Lewis, J. B., Riddle, M. C., Voors, A. A., Metra, M., Lund, L. H., Komajda, M., Testani, J. M., Wilcox, C. S., Ponikowski, P., Lopes, R. D., Verma, S., Lapuerta, P., & Pitt, B. (2021). Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. New England Journal of Medicine, 384(2), 117–128. https://doi.org/10.1056/nejmoa2030183

Bramlage, P., Vijayan, A., Varghese, T. P., Melepurakkal Sadanandan, D., Lanzinger, S., & Rodriguez, C. F. (2025). Comparative analysis on renal and cardiovascular outcomes of antidiabetic treatment in chronic kidney disease patients-A systematic review and network meta-analysis. Diabetes, Obesity & Metabolism, 27(11), 6254–6263. https://doi.org/10.1111/dom.70010

Cannon, C. P., Pratley, R., Dagogo-Jack, S., Mancuso, J., Huyck, S., Masiukiewicz, U., Charbonnel, B., Frederich, R., Gallo, S., Cosentino, F., Shih, W. J., Gantz, I., Terra, S. G., Cherney, D. Z. I., & McGuire, D. K. (2020). Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. The New England Journal of Medicine, 383(15), 1425–1435. https://doi.org/10.1056/nejmoa2004967

Cherney, D., Lund, S. S., Perkins, B. A., Groop, P. H., Cooper, M. E., Kaspers, S., Pfarr, E., Woerle, H. J., & von Eynatten, M. (2016). The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia, 59(9), 1860–1870. https://doi.org/10.1007/s00125-016-4008-2

Einarson, T. R., Acs, A., Ludwig, C., & Panton, U. H. (2018). Prevalence of cardiovascular disease in type 2 diabetes: A systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovascular Diabetology, 17(83), 1-19. https://doi.org/10.1186/s12933-018-0728-6

Engström, A., Söderling, J., Hviid, A., Eliasson, B., Gudbjörnsdottir, S., Wintzell, V., Hveem, K., Jonasson, C., Melbye, M., Pasternak, B., & Ueda, P. (2024). Comparative cardiovascular and renal effectiveness of empagliflozin and dapagliflozin: Scandinavian cohort study. European Heart Journal-Cardiovascular Pharmacotherapy, 10(5), 432–443.

https://doi.org/10.1093/ehjcvp/pvae045

Felix, N., Gauza, M. M., Teixeira, L., Guisso, M. E. S., Nogueira, A., Dagostin, C. S., Godoi, A., Ribeiro, S. A. G., Duque, J. C., Moura-Neto, J. A., & Cardoso, R. (2024a). Cardiovascular outcomes of sodium-glucose cotransporter-2 inhibitors therapy in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and updated meta-analysis. Korean Circulation Journal, 54(9), 549. https://doi.org/10.4070/kcj.2023.0241

Fenta, E. T., Eshetu, H. B., Kebede, N., Bogale, E. K., Zewdie, A., Kassie, T. D., Anagaw, T. F., Mazengia, E. M., & Gelaw, S. S. (2023). Prevalence and predictors of chronic kidney disease among type 2 diabetic patients worldwide, systematic review and meta- analysis. Diabetology and Metabolic Syndrome, 15(1), 1-12. https://doi.org/10.1186/s13098-023-01202-x

Fitchett, D., Zinman, B., Wanner, C., Lachin, J. M., Hantel, S., Salsali, A., Johansen, O. E., Woerle, H. J., Broedl, U. C., & Inzucchi, S. E. (2016). Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. European Heart Journal, 37(19), 1526–1534. https://doi.org/10.1093/eurheartj/ehv728

Heerspink, H. J. L., Stefánsson, B. V., Correa-Rotter, R., Chertow, G. M., Greene, T., Hou, F.-F., Mann, J. F. E., McMurray, J. J. V., Lindberg, M., Rossing, P., Sjöström, C. D., Toto, R. D., Langkilde, A.-M., & Wheeler, D. C. (2020). Dapagliflozin in patients with chronic kidney disease. New England Journal of Medicine, 383(15), 1436–1446. https://doi.org/10.1056/nejmoa2024816

Jhund, P. S., Solomon, S. D., Docherty, K. F., Heerspink, H. J. L., Anand, I. S., Böhm, M., Chopra, V., De Boer, R. A., Desai, A. S., Ge, J., Kitakaze, M., Merkley, B., O’Meara, E., Shou, M., Tereshchenko, S., Verma, S., Vinh, P. N., Inzucchi, S. E., Køber, L., … McMurray, J. J. V. (2021). Efficacy of dapagliflozin on renal function and outcomes in patients with heart failure with reduced ejection fraction: results of DAPA-HF. Circulation, 143(4), 298–309. https://doi.org/10.1161/CIRCULATIONAHA.120.050391

Karagiannis, T., Tsapas, A., Athanasiadou, E., Avgerinos, I., Liakos, A., Matthews, D. R., & Bekiari, E. (2021). GLP-1 receptor agonists and SGLT2 inhibitors for older people with type 2 diabetes: A systematic review and meta-analysis. Diabetes Research and Clinical Practice, 174, 108737. https://doi.org/10.1016/j.diabres.2021.108737

Komuro, I., Kadowaki, T., Bodegård, J., Thuresson, M., Okami, S., & Yajima, T. (2021). Lower heart failure and chronic kidney disease risks associated with sodium-glucose cotransporter-2 inhibitor use in Japanese type 2 diabetes patients without established cardiovascular and renal diseases. Diabetes, Obesity & Metabolism, 23 Suppl 2(S2), 19–27. https://doi.org/10.1111/dom.14119

Mahaffey, K. W., Jardine, M. J., Bompoint, S., Cannon, C. P., Neal, B., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Capuano, G., De Zeeuw, D., Greene, T., Levin, A., Pollock, C., Sun, T., Wheeler, D. C., Yavin, Y., … Perkovic, V. (2019). Canagliflozin and cardiovascular and renal outcomes in type 2 diabetes mellitus and chronic kidney disease in primary and secondary cardiovascular prevention groups: Results from the randomized CREDENCE trial. Circulation, 140(9), 739–750. https://doi.org/10.1161/CIRCULATIONAHA.119.042007

Martens, F. M. A. C., Visseren, F. L. J., Westerink, J., Spee, R. F., Saloua, E. M., Mosterd, A., Handoko, L. M., Leening, M. J. G., Römer, T. J., Slootweg, A., van Bon, A. C., & Hemels, M. E. W. (2025). 2023 European Society of Cardiology guidelines for the management of cardiovascular disease in patients with diabetes: Statement of endorsement by the NVVC. Netherlands Heart Journal, 33(7–8), 216–225. https://doi.org/10.1007/s12471-025-01967-y

Marx, N., Federici, M., Schütt, K., Müller-Wieland, D., Ajjan, R. A., Antunes, M. J., Christodorescu, R. M., Crawford, C., Di Angelantonio, E., Eliasson, B., Espinola-Klein, C., Fauchier, L., Halle, M., Herrington, W. G., Kautzky-Willer, A., Lambrinou, E., Lesiak, M., Lettino, M., McGuire, D. K., … Zeppenfeld, K. (2023). 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes: Developed by the task force on the management of cardiovascular disease in patients with diabetes of the European Society of Cardiology (ESC). European Heart Journal, 44(39), 4043–4140. https://doi.org/10.1093/eurheartj/ehad192

McGuire, D. K., Shih, W. J., Cosentino, F., Charbonnel, B., Cherney, D. Z. I., Dagogo-Jack, S., Pratley, R., Greenberg, M., Wang, S., Huyck, S., Gantz, I., Terra, S. G., Masiukiewicz, U., & Cannon, C. P. (2021). Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: A meta-analysis. JAMA Cardiology, 6(2), 148–158. https://doi.org/10.1001/jamacardio.2020.4511

Mordi, N. A., Mordi, I. R., Singh, J. S., McCrimmon, R. J., Struthers, A. D., & Lang, C. C. (2020). Renal and cardiovascular effects of sglt2 inhibition in combination with loop diuretics in patients with type 2 diabetes and chronic heart failure: The RECEDE- CHF Trial. Circulation, 142(18), 1713–1724. https://doi.org/10.1161/CIRCULATIONAHA.120.048739

Neal, B., Perkovic, V., Mahaffey, K. W., de Zeeuw, D., Fulcher, G., Erondu, N., Shaw, W., Law, G., Desai, M., & Matthews, D. R. (2017). Canagliflozin and cardiovascular and renal events in type 2 diabetes. New England Journal of Medicine, 377(7), 644–657. https://doi.org/10.1056/nejmoa1611925

Neuen, B. L., Ohkuma, T., Neal, B., Matthews, D. R., De Zeeuw, D., Mahaffey, K. W.,Fulcher, G., Desai, M., Li, Q., Deng, H., Rosenthal, N., Jardine, M. J., Bakris, G., & Perkovic, V. (2018). Cardiovascular and renal outcomes with canagliflozin according to baseline kidney function data from the CANVAS program. Circulation, 138(15),1537–1550. https://doi.org/10.1161/CIRCULATIONAHA.118.035901

Perkovic, V., de Zeeuw, D., Mahaffey, K. W., Fulcher, G., Erondu, N., Shaw, W., Barrett, T. D., Weidner-Wells, M., Deng, H., Matthews, D. R., & Neal, B. (2018). Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomized clinical trials. The Lancet Diabetes and Endocrinology, 6(9), 691–704. https://doi.org/10.1016/S2213-8587(18)30141-4

Perkovic, V., Jardine, M.J., Neal, B., Bompoint, S., Heerspink, H.J.L., Charytan, D.M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Cannon, C.P., Capuano, G., Chu, P.-L., De Zeeuw, D., Greene, T., Levin, A., Pollock, C., Wheeler, D.C., Yavin, Y., Zhang, H., Zinman, B., Meininger, G., Brenner, B.M., Mahaffey, K.W., 2019. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. New England Journal of Medicine, 380, 2295–2306. https://doi.org/10.1056/nejmoa1811744

Qiu, M., Ding, L., & Zhou, H. (2021). Effects of SGLT2 inhibitors on cardiovascular and renal outcomes in type 2 diabetes: A meta-analysis with trial sequential analysis. Medicine, 100(10), E25121. https://doi.org/10.1097/MD.0000000000025121

Ueda, P., Svanström, H., Melbye, M., Eliasson, B., Svensson, A. M., Franzén, S., Gudbjörnsdottir, S., Hveem, K., Jonasson, C., & Pasternak, B. (2018). Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register-based cohort study. BMJ (Clinical Research Ed.), 363. https://doi.org/10.1136/bmj.k4365

Verma, S., & McMurray, J. J. V. (2018). SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia, 61(10), 2108–2117. https://doi.org/10.1007/s00125-018-4670-7

Vianini, E., Pandey, A., Rolland, C., Ngubane, N., Mueller-Wieland, D., Gilbert, J., & Ahmad, A. (2025). Systematic literature review of the impact of type 2 diabetes and heart failure guideline adherence on clinical and economic outcomes. Diabetes Therapy, 16(5), 851–864. https://doi.org/10.1007/S13300-025-01725-8

Wanner, C., Inzucchi, S. E., Lachin, J. M., Fitchett, D., von Eynatten, M., Mattheus, M., Johansen, O. E., Woerle, H. J., Broedl, U. C., & Zinman, B. (2016). Empagliflozin and progression of kidney disease in type 2 diabetes. New England Journal of Medicine, 375(4), 323–334. https://doi.org/10.1056/nejmoa1515920

Wiviott, S. D., Raz, I., Bonaca, M. P., Mosenzon, O., Kato, E. T., Cahn, A., Silverman, M. G.,Zelniker, T. A., Kuder, J. F., Murphy, S. A., Bhatt, D. L., Leiter, L. A., McGuire, D. K., Wilding, J. P. H., Ruff, C. T., Gause-Nilsson, I. A. M., Fredriksson, M., Johansson, P. A., Langkilde, A.-M., & Sabatine, M. S. (2019). Dapagliflozin and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine, 380(4), 347–357. https://doi.org/10.1056/nejmoa1812389

World Health Organization. (2016). Global report on diabetes. Geneva: World Health Organization. https://www.who.int/publications/i/item/9789241565257.

World Health Organization. (2020). HEARTS D: diagnosis and management of type 2 diabetes. Geneva: World Health Organization. https://www.who.int/publications/i/item/who-ucn-ncd-20.1.

World Health Organization. (2024, November 14). Diabetes. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/diabetes.

Xie, D., You, F., Li, C., Zhou, D., Yang, L., & Liu, F. (2025). Global regional, and national burden of type 2 diabetes attributable to dietary factors from 1990 to 2021. Sci Rep, 15, 13278 (2025). https://doi.org/10.1038/s41598-025-98022-y

Yale, J. F., Bakris, G., Cariou, B., Nieto, J., David-Neto, E., Yue, D., Wajs, E., Figueroa, K., Jiang, J., Law, G., Usiskin, K., & Meininger, G. (2014). Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes mellitus and chronic kidney disease. Diabetes, Obesity and Metabolism, 16(10), 1016–1027. https://doi.org/10.1111/dom.12348

Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., Broedl, U. C., & Inzucchi, S. E. (2015). Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. The New England Journal of Medicine, 373(22), 17–18. https://doi.org/10.1056/nejmoa1504720

Downloads

Published

2026-07-27

How to Cite

Chelsy Vanya Br. Meliala, Tuba, S., Adi Priyono, Syed Azhar Syed Sulaiman, Budi Sumaryono, & Endah Permata Sari. (2026). Impact of SGLT2 inhibitors on heart failure risk and kidney function in type 2 diabetic mellitus patients: A literature review. International Journal of Applied Mathematics, Sciences, and Technology for National Defense, 4(2), 95-106. https://doi.org/10.58524/app.sci.def.v4i2.1134