Effect of SGLT-2 Inhibitor Therapy on Cardiovascular Health in Diabetes Mellitus Patients

  • Gusti Destiana Universitas Lampung
Keywords: cardiovascular, diabetes mellitus, SGLT-2 inhibitor


Cardiovascular disease has become a major cause of mortality and morbidity in patients with type 2 diabetes mellitus. The main factors that increase the risk of cardiovascular disease include chronic hyperglycemia, decreased insulin sensitivity, visceral adiposity, and particularly hypertensive comorbidity and increased arterial stiffness. Meanwhile, sodium-glucose co-transporter-2 inhibitors, a new category in diabetes therapy are known to reduce blood glucose in patients by increasing glycosuria through inhibition of urinary glucose reabsorption. The therapy also produces glucose-induced osmotic diuresis, weight loss, and lowered blood pressure. The aim of this literature review is to determine the effect of sodium-glucose co-transporter-2 inhibitors on cardiovascular health in diabetes mellitus patients. This study is a literature review involving 20 literature sources from 3 national journals and 17 international journals with the keywords used include diabetes mellitus, cardiovascular and SGLT-2 inhibitors. Several studies have significantly demonstrated the effect of SGLT-2 inhibitors on cardiovascular health, as seen by a reduction in mortality and hospitalization of heart failure, better blood pressure and renal outcome, improved heart function in diabetic cardiomyopathy and myocardial ischemia.


Ahmed, H. M., Khraishah, H., & Cho, L. (2018). Cardioprotective anti-hyperglycaemic medications: a review of clinical trials. European Heart Journal, 39(25), 2368c-2375c. https://doi.org/10.1093/eurheartj/ehx668

Amandari, I. G. A. A. E., Sarasmita, M. A., Dewi, N. P. U. S., & Krisnayanti, M. W. (2018). SGLT-2 inhibitor: pilihan terapi baru untuk penderita DM tipe 2. Hang Tuah Medical Journal, 16(1), 28–36.

Aziz, W. A., Muriman, L. Y., & Burhan, S. R. (2020). Hubungan antara tingkat pengetahuan dengan gaya hidup pada penderita diabetes melitus. Jurnal Penelitian Perawat Profesional, 2(1), 105–114.

Bullard, K. M., Cowie, C. C., Lessem, S. E., Saydah, S. H., Menke, A., Geiss, L. S., Orchard, T. J., Rolka, D. B., & Imperatore, G. (2016). Morbidity and Mortality Weekly Report Prevalence of Diagnosed Diabetes in Adults by Diabetes Type-United States, 2016. Morbidity and Mortality Weekly Report, 67(12), 2016–2018. https://doi.org/10.1097/EDE.0b013e31829ef01a

Chamberlain, J. J., Herman, W. H., Leal, S., Rhinehart, A. S., Shubrook, J. H., Skolnik, N., & Kalyani, R. R. (2017). Pharmacologic therapy for type 2 diabetes: Synopsis of the 2017 American diabetes association standards of medical care in diabetes. Annals of Internal Medicine, 166(8), 572–578. https://doi.org/10.7326/M16-2937

Filippas-Ntekouan, S., Tsimihodimos, V., Filippatos, T., Dimitriou, T., & Elisaf, M. (2018). SGLT-2 inhibitors: pharmacokinetics characteristics and effects on lipids. Expert Opinion on Drug Metabolism and Toxicology, 14(11), 1113–1121. https://doi.org/10.1080/17425255.2018.1541348

Kaplan, A., Abidi, E., El-Yazbi, A., Eid, A., Booz, G. W., & Zouein, F. A. (2018). Direct cardiovascular impact of SGLT2 inhibitors: mechanisms and effects. Heart Failure Reviews, 23(3), 419–437. https://doi.org/10.1007/s10741-017-9665-9

Kosiborod, M., Cavender, M. A., Fu, A. Z., Wilding, J. P., Khunti, K., Holl, R. W., Norhammar, A., Birkeland, K. I., Jørgensen, M. E., Thuresson, M., Arya, N., Bodegård, J., Hammar, N., & Fenici, P. (2017). Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: The CVD-REAL study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotranspo. Circulation, 136(3), 249–259. https://doi.org/10.1161/CIRCULATIONAHA.117.029190

Kosiborod, M., Lam, C. S. P., Kohsaka, S., Kim, D. J., Karasik, A., Shaw, J., Tangri, N., Goh, S. Y., Thuresson, M., Chen, H., Surmont, F., Hammar, N., Fenici, P., Kosiborod, M., Cavender, M. A., Fu, A. Z., Wilding, J. P., Khunti, K., Norhammar, A., … Magliano, D. (2018). Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL 2 Study. Journal of the American College of Cardiology, 71(23), 2628–2639. https://doi.org/10.1016/j.jacc.2018.03.009

Kusaka, H., Koibuchi, N., Hasegawa, Y., Ogawa, H., & Kim-Mitsuyama, S. (2016). Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome. Cardiovascular Diabetology, 15(1), 1–14. https://doi.org/10.1186/s12933-016-0473-7

Lahnwong, S., Chattipakorn, S. C., & Chattipakorn, N. (2018). Potential mechanisms responsible for cardioprotective effects of sodium-glucose co-transporter 2 inhibitors. Cardiovascular Diabetology, 17(1), 1–17. https://doi.org/10.1186/s12933-018-0745-5

Made, P., & Pathni, S. D. (2019). Terapi Diabetes dengan SGLT-2 Inhibitor. Cdk-277, 46(6), 452–456.

Monami, M., Dicembrini, I., & Mannucci, E. (2017). Effects of SGLT-2 inhibitors on mortality and cardiovascular events: a comprehensive meta-analysis of randomized controlled trials. Acta Diabetologica, 54(1), 19–36. https://doi.org/10.1007/s00592-016-0892-7

Sarafidis, P., Ferro, C. J., Morales, E., Ortiz, A., Malyszko, J., Hojs, R., Khazim, K., Ekart, R., Valdivielso, J., Fouque, D., London, G. M., Massy, Z., Ruggenenti, P., Porrini, E., Wiecek, A., Zoccali, C., Mallamaci, F., & Hornum, M. (2019). SGLT-2 inhibitors and GLP-1 receptor agonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease. A consensus statement by the EURECA-m and the DIABESITY working groups of the ERA-EDTA. Nephrology Dialysis Transplantation, 34(2), 208–230. https://doi.org/10.1093/ndt/gfy407

Scheen, A. J. (2018). Cardiovascular effects of new oral glucose-lowering agents DPP-4 and SGLT-2 inhibitors. Circulation Research, 122(10), 1439–1459. https://doi.org/10.1161/CIRCRESAHA.117.311588

Striepe, K., Jumar, A., Ott, C., Karg, M. V., Schneider, M. P., Kannenkeril, D., & Schmieder, R. E. (2017). Effects of the selective sodium-glucose cotransporter 2 inhibitor empagliflozin on vascular function and central hemodynamics in patients with type 2 diabetes mellitus. Circulation, 136(12), 1167–1169. https://doi.org/10.1161/CIRCULATIONAHA.117.029529

Verma, S., Mazer, C. D., Fitchett, D., Inzucchi, S. E., Pfarr, E., George, J. T., & Zinman, B. (2018). Empagliflozin reduces cardiovascular events, mortality and renal events in participants with type 2 diabetes after coronary artery bypass graft surgery: subanalysis of the EMPA-REG OUTCOME® randomised trial. Diabetologia, 61(8), 1712–1723. https://doi.org/10.1007/s00125-018-4644-9

Woo, V., Connelly, K., Lin, P., & McFarlane, P. (2019). The role of sodium glucose cotransporter-2 (SGLT-2) inhibitors in heart failure and chronic kidney disease in type 2 diabetes. Current Medical Research and Opinion, 35(7), 1283–1295. https://doi.org/10.1080/03007995.2019.1576479

Zinman, B., Inzucchi, S. E., Lachin, J. M., Wanner, C., Ferrari, R., Fitchett, D., Bluhmki, E., Hantel, S., Kempthorne-Rawson, J., Newman, J., Johansen, O. E., Woerle, H. J., & Broedl, U. C. (2014). Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOMETM). Cardiovascular Diabetology, 13(1), 1–8. https://doi.org/10.1186/1475-2840-13-102

Zou, C. Y., Liu, X. K., Sang, Y. Q., Wang, B., & Liang, J. (2019). Effects of SGLT2 inhibitors on cardiovascular outcomes and mortality in type 2 diabetes: A meta-analysis. Medicine (United States), 98(49). https://doi.org/10.1097/MD.0000000000018245

How to Cite
Destiana, G. (2020). Effect of SGLT-2 Inhibitor Therapy on Cardiovascular Health in Diabetes Mellitus Patients. Jurnal Penelitian Perawat Profesional, 2(4), 513-522. https://doi.org/10.37287/jppp.v2i4.207