DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20175669

Empagliflozin: an exciting prospect in the treatment of diabetes

Melvin George, Karthik Srinivas, Damal Kandadai Sriram

Abstract


Type 2 diabetes mellitus (T2DM) continues to be a chronic and disabling disease that is associated with high mortality and morbidity. The epidemic burden of diabetes mellitus has increased in developing countries and Asia is considered as the “diabetic epicentre”. Type 2 diabetes (T2DM), is characterised by reduced secretion of insulin from pancreatic beta cells independently or associated with reduced response of peripheral tissues to circulating insulin. A proper glycaemic control is essential to delay the micro and macrovascular complications of T2DM. Standard anti-diabetic agents including insulin happen to induce minor to major adverse outcomes in certain populations over prolonged period of administration. Hence there has been a compelling need to develop newer and novel approach to treatment of T2DM. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a novel category of drugs that happen to reduce glycaemic overload by inducing glycosuria. The safety, efficacy and tolerability profile of these drugs were studied separately under various trials and was approved for use in August 2014 by US-FDA. This review is an attempt to describe the history of SGLT-2 inhibitors, their mechanism of action, safety and efficacy as well as its current status among anti-diabetic agents.  


Keywords


Complications, Diabetes, Empagliflozin, Efficacy, SGLT2 inhibitors

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References


Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus- present and future perspectives. Nat Rev Endocrinol. 2011;8(4):228-36.

Thrasher J. Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies. Am J Cardiol. 2017;120(1S):S4-16.

Santos LL, Lima FJC de, Sousa-Rodrigues CF de, Barbosa FT. Use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus. Rev Assoc Medica Bras. 2017;63(7):636-41.

Filippatos TD, Liberopoulos EN, Elisaf MS. Dapagliflozin in patients with type 2 diabetes mellitus. Ther Adv Endocrinol Metab. 2015;6(1):29-41.

Fujita Y, Inagaki N. Renal sodium glucose cotransporter 2 inhibitors as a novel therapeutic approach to treatment of type 2 diabetes: Clinical data and mechanism of action. J Diabetes Investig. 2014; 5(3):265-75.

Munir KM, Davis SN. Differential pharmacology and clinical utility of empagliflozin in type 2 diabetes. Clin Pharmacol Adv Appl. 2016;8:19-34.

Wood IS, Trayhurn P. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr. 2003; 89(1):3-9.

Roden M, Weng J, Eilbracht J, Delafont B, Kim G, Woerle HJ, 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):208-19.

Tikkanen I, Narko K, Zeller C, Green A, Salsali A, Broedl UC, et al. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabet Care. 2015;38(3):420-8.

Heise T, Seewaldt-Becker E, Macha S, Hantel S, Pinnetti S, Seman L, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks’ treatment with empagliflozin once daily in patients with type 2 diabetes. Diabet Obes Metab. 2013;15(7):613-21.

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.

Ferrannini E, Seman L, Seewaldt-Becker E, Hantel S, Pinnetti S, Woerle HJ. A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes. Diabet Obes Metab. 2013;15(8):721-8.

Brand T, Macha S, Mattheus M, Pinnetti S, Woerle HJ. Pharmacokinetics of empagliflozin, a sodium glucose cotransporter-2 (SGLT-2) inhibitor, co-administered with sitagliptin in healthy volunteers. Adv Ther. 2012;29(10):889-99.

Hadjadj S, Rosenstock J, Meinicke T, Woerle HJ, Broedl UC. Initial Combination of Empagliflozin and Metformin in Patients with Type 2 Diabetes. Diabet Care. 2016;39(10):1718-28.

Kovacs CS, Seshiah V, Swallow R, Jones R, Rattunde H, Woerle HJ, et al. Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial. Diabet Obes Metab. 2014;16(2):147-58.

Rosenstock J, Jelaska A, Zeller C, Kim G, Broedl UC, Woerle HJ, et al. Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78-week randomized, double-blind, placebo-controlled trial. Diabet Obes Metab. 2015;17(10):936-48.

Kosiborod M, Cavender MA, Fu AZ, Wilding JP, Khunti K, Holl RW, 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):249-59.

Skrtić M, Yang GK, Perkins BA, Soleymanlou N, Lytvyn Y, von Eynatten M, et al. Characterisation of glomerular haemodynamic responses to SGLT2 inhibition in patients with type 1 diabetes and renal hyperfiltration. Diabetol. 2014;57(12):2599-602.

Cherney DZI, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014;129(5):587-97.

Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016;375(4):323-34.

Shiba T, Ishii S, Okamura T, Mitsuyoshi R, Pfarr E, Koiwai K. Efficacy and safety of empagliflozin in Japanese patients with type 2 diabetes mellitus: A sub-analysis by body mass index and age of pooled data from three clinical trials. Diabetes Res Clin Pract. 2017;131:169-78.

Kohler S, Zeller C, Iliev H, Kaspers S. Safety and Tolerability of Empagliflozin in Patients with Type 2 Diabetes: Pooled Analysis of Phase I-III Clinical Trials. Adv Ther. 2017;34(7):1707-26.

Highlights of prescribing information. These highlights do not include all the information needed to use JARDIANCE safely and effectively, 2016. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204629s008lbl.pdf. Accessed 6 November 2017.

Highlights of prescribing information. These highlights do not include all the information needed to use FARXIGA safely and effectively, 2014. Available at:https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202293s000lbl.pdf. Accessed 6 November 2017.

Highlights of prescribing information. These highlights do not include all the information needed to use INVOKANA® safely and effectively, 2017. Available at: https://www.invokana.com/prescribing-information.pdf. Accessed 6 November 2017.

ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/results?term=Empagliflozin. Accessed 6 November 2017.

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.

Plosker GL. Canagliflozin: a review of its use in patients with type 2 diabetes mellitus. Drugs. 2014;74(7):807-24.

Minze MG, Will K, Terrell BT, Black RL, Irons BK. Benefits of SGLT2 Inhibitors beyond glycemic control - A focus on metabolic, cardiovascular, and renal outcomes. Curr Diabet Rev. 2017.

Kumana CR, Tan KCB, Cheung BMY. Absolute benefits of empagliflozin in type 2 diabetes: a game changer? Postgrad Med J. 2017;93(1101):373-5.

Fioretto P, Avogaro A. Dapagliflozin: potential beneficial effects in the prevention and treatment of renal and cardiovascular complications in patients with type 2 diabetes. Expert Opin Pharmacother. 2017;18(5):517-27.