Review of the evidence base of representatives of the group of sodium-glucose co-transporter 2 inhibitors available at the Ukrainian market (literature review)

Main Article Content

K.O. Zuiev


The article presents an analysis of the results of randomized clinical studies of glucose lowering drugs from the class of sodium-glucose transport protein 2 inhibitors in patients with type 2 diabetes: EMPA-REG OUTCOME® with empagliflozin and DECLARE-TIMI 58® with dapagliflozin. It is shown how the results of these trials have influenced the formation of the latest algorithms for antihyperglycemic therapy of patients with type 2 diabetes.

Article Details

How to Cite
Zuiev, K. “Review of the Evidence Base of Representatives of the Group of Sodium-Glucose Co-Transporter 2 Inhibitors Available at the Ukrainian Market (literature Review)”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 16, no. 3, Apr. 2020, pp. 237-44, doi:10.22141/2224-0721.16.3.2020.205273.
Literature Review


Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117‐2128. doi:10.1056/NEJMoa1504720.

Patorno E, Pawar A, Franklin JM, et al. Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care. Circulation. 2019;139(25):2822‐2830. doi:10.1161/CIRCULATIONAHA.118.039177.

Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347‐357. doi:10.1056/NEJMoa1812389.

McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995‐2008. doi:10.1056/NEJMoa1911303. 

Kosiborod M, Cavender MA, Fu AZ, et al. 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 Cotransporter-2 Inhibitors). Circulation. 2017;136(3):249‐259. doi:10.1161/CIRCULATIONAHA.117.029190.

Ridderstråle M, Andersen KR, Zeller C, et al. Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial [published correction appears in Lancet Diabetes Endocrinol. 2015 Sept;3(9):e7]. Lancet Diabetes Endocrinol. 2014;2(9):691‐700. doi:10.1016/S2213-8587(14)70120-2.

Nauck MA, Del Prato S, Meier JJ, et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care. 2011;34(9):2015‐2022. doi:10.2337/dc11-0606.

Sjöström CD, Johansson P, Ptaszynska A, List J, Johnsson E. Dapagliflozin lowers blood pressure in hypertensive and non-hypertensive patients with type 2 diabetes. Diab Vasc Dis Res. 2015;12(5):352‐358. doi:10.1177/1479164115585298.

Roden M, Weng J, Eilbracht J, et al. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2013;1(3):208‐219. doi:10.1016/S2213-8587(13)70084-6.

Levine MJ. Empagliflozin for Type 2 Diabetes Mellitus: An Overview of Phase 3 Clinical Trials. Curr Diabetes Rev. 2017;13(4):405‐423. doi:10.2174/1573399812666160613113556.

Blonde L, Stenlöf K, Fung A, Xie J, Canovatchel W, Meininger G. Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks. Postgrad Med. 2016;128(4):371‐380. doi:10.1080/00325481.2016.1169894.

Sugiyama S, Jinnouchi H, Kurinami N, et al. Dapagliflozin Reduces Fat Mass without Affecting Muscle Mass in Type 2 Diabetes. J Atheroscler Thromb. 2018;25(6):467‐476. doi:10.5551/jat.40873.

Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366(9493):1279‐1289. doi:10.1016/S0140-6736(05)67528-9.

ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560‐2572. doi:10.1056/NEJMoa0802987.

Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129‐139. doi:10.1056/NEJMoa0808431.

Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545‐2559. doi:10.1056/NEJMoa0802743.

United Kingdom Prospective Diabetes Study 24: a 6-year, randomized, controlled trial comparing sulfonylurea, insulin, and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy. United Kingdom Prospective Diabetes Study Group. Ann Intern Med. 1998;128(3):165‐175. doi:10.7326/0003-4819-128-3-199802010-00001.

White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369(14):1327‐1335. doi:10.1056/NEJMoa1305889.

Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317‐1326. doi:10.1056/NEJMoa1307684.

Green JB, Bethel MA, Armstrong PW, et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015;373(3):232‐242. doi:10.1056/NEJMoa1501352.

Rosenstock J, Perkovic V, Johansen OE, et al. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial. JAMA. 2019;321(1):69‐79. doi:10.1001/jama.2018.18269.

Zoungas S, Lambers Heerspink HJ, Chalmers J, et al. Intensive glucose lowering and end stage kidney disease: new data from the ADVANCE trial. Diabetologia. 2011;54(Suppl 1):S23. doi:10.1007/s00125-011-2276-4.

Perkovic V, Heerspink HL, Chalmers J, et al. Intensive glucose control improves kidney outcomes in patients with type 2 diabetes. Kidney Int. 2013;83(3):517‐523. doi:10.1038/ki.2012.401.

Neal B, Perkovic V, Matthews DR. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(21):2099. doi:10.1056/NEJMc1712572.

Davies MJ, D'Alessio DA, Fradkin J, et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669‐2701. doi:10.2337/dci18-0033.

Furtado RHM, Bonaca MP, Raz I, et al. Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction. Circulation. 2019;139(22):2516‐2527. doi:10.1161/CIRCULATIONAHA.119.039996.

Fitchett D, Inzucchi SE, Cannon CP, et al. Empagliflozin Reduced Mortality and Hospitalization for Heart Failure Across the Spectrum of Cardiovascular Risk in the EMPA-REG OUTCOME Trial. Circulation. 2019;139(11):1384‐1395. doi:10.1161/CIRCULATIONAHA.118.037778.

Kato ET, Silverman MG, Mosenzon O, et al. Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus. Circulation. 2019;139(22):2528‐2536. doi:10.1161/CIRCULATIONAHA.119.040130.

Fitchett D, Zinman B, Wanner C, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur Heart J. 2016;37(19):1526‐1534. doi:10.1093/eurheartj/ehv728.

Bajaj HS, Raz I, Mosenzon O, et al. Cardiovascular and renal benefits of dapagliflozin in patients with short and long-standing type 2 diabetes: Analysis from the DECLARE-TIMI 58 trial. Diabetes Obes Metab. 2020;10.1111/dom.14011. doi:10.1111/dom.14011.

Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41(2):255‐323. doi:10.1093/eurheartj/ehz486.

Nichols GA, Hillier TA, Erbey JR, Brown JB. Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care. 2001;24(9):1614‐1619. doi:10.2337/diacare.24.9.1614.