Review Article
Sodium-Glucose Cotransporter 2 Inhibitors: The New Option for Diabetes Mellitus Management
Abstract
Type 2 diabetes mellitus continues to be a challenging disease to manage successfully. Beyond the first-line option metformin, there are a number of classes of medications from which to select. This article reviews the new sodium-glucose cotransporter 2 inhibitors canagliflozin and dapagliflozin, including their benefits, adverse effects, and potential place in therapy. Upon review, the use of these medications has led to an A1c reduction between -0.37% and -1.16%. These medications also have been shown to reduce A1c when used with insulin. Some adverse effects were noted when using canagliflozin and dapagliflozin, with the most frequent being urinary tract infections and genital mycotic infections. We review the sodium-glucose cotransporter 2 inhibitors approved by the US Food and Drug Administration and their potential roles in the management of type 2 diabetes mellitus.This content is limited to qualifying members.
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References
1. American Diabetes Association. Standards of medical care in Diabetes--2014. Diabetes Care 2014;37(Suppl 1):S14-S80.
2. Chao EC, Henry RR. SGLT2 inhibitionVa novel strategy for diabetes treatment. Nat Rev Drug Discov 2010;9:551-559.
3. Wright EM. Renal Na(+)-glucose cotransporters. Am J Physiol Renal Physiol 2001;280:F10-F18.
4. Mackenzie B, Loo DD, Panayotova-Heiermann M, et al. Biophysical characteristics of the pig kidney Na+/glucose cotransporter SGLT2 reveal a common mechanism for SGLT1 and SGLT2. J Biol Chem 1996;271:32678-32683.
5. Kanai Y, Lee WS, You G, et al. The human kidney low affinity Na+/ glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J Clin Invest 1994;93:397-404.
6. Farber SJ, Berger EY, Earle DP. Effect of diabetes and insulin of the maximum capacity of the renal tubules to reabsorb glucose. J Clin Invest 1951;30:125-129.
7. Sha S, Devineni D, Ghosh A, et al. Canagliflozin, a novel inhibitor of sodium glucose co-transporter 2, dose dependently reduces calculated renal threshold for glucose excretion and increases urinary glucose excretion in healthy subjects. Diabetes Obes Metab 2011;13:669-672.
8. Invokana (canagliflozin) [package insert]. Titusville, NJ, Janssen Pharmaceuticals, 2014.
9. Farxiga (dapagliflozin) [package insert]. Princeton, NJ, Bristol-Myers Squibb, 2014.
10. Stenlof K, Cefalu WT, Kim KA, et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab 2013;15:372-382.
11. Rosenstock J, Aggarwal N, Polidori D, et al. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes. Diabetes Care 2012;35:1232-1238.
12. Schernthaner G, Gross JL, Rosenstock J, et al. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care 2013;36:2508-2515.
13. Yale JF, Bakris G, Cariou B, et al. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab 2013;15:463-473.
14. Devineni D, Morrow L, Hompesch M, et al. Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin. Diabetes Obes Metab 2012;14:539-545.
15. Bode B, Stenlof K, Sullivan D, et al. Efficacy and safety of canagliflozin treatment in older subjects with type 2 diabetes mellitus: a randomized trial. Hosp Pract (1995)2013;41:72-84.
16. Ferrannini E, Ramos SJ, Salsali A, et al. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care 2010;33:2214-2224.
17. Bailey CJ, Gross JL, Pieters A, et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomized, double-blind, placebo controlled trial. Lancet 2010;375:2223-2233.
18. 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;34:2015-2022.
19. Strojek K, Yoon KH, Hruba V, et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab 2011;13:928-938.
20. Wilding JP, Norwood P, T’joen C, et al. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care 2009;32:1656-1662.
21. Wilding JP, Woo V, Soler NG, et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med 2012;156:405-415.
22. Kaku K, Kiyosue A, Inoue S, et al. Efficacy and safety of dapagliflozin monotherapy in Japanese patients with type 2 diabetes inadequately controlled with diet and exercise. Diabetes Obes Metab 2014;16:1102-1110.
23. Ji L, Ma J, Li H, et al. Dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes mellitus: a randomized, blinded, prospective phase III study. Clin Ther2014;36:84-100.e9.
24. Bailey CJ, Iqbal N, T’joen C, et al. Dapagliflozin monotherapy in drug-naive patients with diabetes: a randomized-controlled trial of low-dose range. Diabetes Obes Metab 2012;14:951-959.
25. Henry RR, Murray AV, Marmolejo MH, et al. Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomized controlled trial. Int J Clin Pract 2012;66:446-456.
26. Rosenstock J, Vico M, Wei L, et al. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care 2012;35:1473-1478.
27. Jabbour SA, Hardy E, Sugg J, et al. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Diabetes Care 2014;37:740-750.
28. Anderson SL, Marrs JC. Dapagliflozin for the treatment of type 2 diabetes. Ann Pharmacother 2012;46:590-598.
29. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Sciences, Office of Biostatistics. Statistical review and evaluation: clinical studies. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000StatR.pdf. Accessed June 26, 2014.
