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Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitor

Sodium Glucose Co-Transporter 2 (SGLT2) 억제제

  • Kim, Mi-Kyung (Paik Institute for Clinical Research, Department of Internal Medicine, Inje University College of Medicine) ;
  • Park, Jeong Hyun (Paik Institute for Clinical Research, Department of Internal Medicine, Inje University College of Medicine)
  • 김미경 (인제대학교 의과대학 내과학교실, 백인제기념임상의학연구소) ;
  • 박정현 (인제대학교 의과대학 내과학교실, 백인제기념임상의학연구소)
  • Published : 2014.07.01

Abstract

Sodium glucose co-transporter 2 (SGLT2) inhibition is a new therapeutic approach for the treatment of type 2 diabetes mellitus, independent of insulin secretion and activity. SGLT2 inhibitors have a unique mechanism of action via inhibition of renal glucose reabsorption, which is different from the mechanisms of prior medications. Clinical trials have supported the efficacy of SGLT2 inhibitors in the reduction of HbA1c as monotherapy or add-on therapy with other existing medications, including insulin. In addition to their glucose-lowering effect, SGLT2 inhibitors can significantly reduce blood pressure and body weight. The most concerning side effects are genital and urinary tract infections, especially in females. SGLT2 inhibitors offer a promising potential strategy for diabetes treatment because they can be combined with nearly any existing anti-diabetic medication, cause less hypoglycemia, and possess additional metabolic benefits beyond glucose level reduction.

Keywords

References

  1. Korean Diabetes Association. Diabetes Facts Sheets in Korea 2013. KDA, 2013
  2. Gerich JE. Physiology of glucose homeostasis. Diabetes Obes Metab 2000;2:345-350. https://doi.org/10.1046/j.1463-1326.2000.00085.x
  3. Meyer C, Dostou JM, Welle SL, Gerich JE. Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis. Am J Physiol Endocrinol Metab 2002;282:E419-427. https://doi.org/10.1152/ajpendo.00032.2001
  4. Meyer C, Stumvoll M, Welle S, Woerle HJ, Haymond M, Gerich J. Relative importance of liver, kidney, and substrates in epinephrine-induced increased gluconeogenesis in humans. Am J Physiol Endocrinol Metab 2003;285:E819-826. https://doi.org/10.1152/ajpendo.00145.2003
  5. Bakris GL, Fonseca VA, Sharma K, Wright EM. Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications. Kidney Int 2009;75:1272-1277. https://doi.org/10.1038/ki.2009.87
  6. Silverman M, Turner J. Glucose transport in the renal proximal tubule. In: Windhager EE, Ed. Handbook of Physiology. New York Oxford University Press, 1992:2017-2038.
  7. Nair S, Wilding JP. Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab 2010;95:34-42. https://doi.org/10.1210/jc.2009-0473
  8. Meyer C, Woerle HJ, Dostou JM, Welle SL, Gerich JE. Abnormal renal, hepatic, and muscle glucose metabolism following glucose ingestion in type 2 diabetes. Am J Physiol Endocrinol Metab 2004;287:E1049-1056. https://doi.org/10.1152/ajpendo.00041.2004
  9. Vestri S, Okamoto MM, de Freitas HS, et al. Changes in sodium or glucose filtration rate modulate expression of glucose transporters in renal proximal tubular cells of rat. J Membr Biol 2001;182:105-112. https://doi.org/10.1007/s00232-001-0036-y
  10. Freitas HS, Anhe GF, Melo KF, et al. Na(+) -glucose transporter-2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: involvement of hepatocyte nuclear factor-1alpha expression and activity. Endocrinology 2008;149:717-724. https://doi.org/10.1210/en.2007-1088
  11. Rahmoune H, Thompson PW, Ward JM, Smith CD, Hong G, Brown J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 2005;54:3427-3434. https://doi.org/10.2337/diabetes.54.12.3427
  12. Kaku K, Inoue S, Matsuoka O, et al. Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control: a phase II multicentre, randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab 2013;15:432-440. https://doi.org/10.1111/dom.12047
  13. Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet 2010;375:2223-2233. https://doi.org/10.1016/S0140-6736(10)60407-2
  14. 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. https://doi.org/10.2337/dc11-0606
  15. Wilding JP, Norwood P, T'joen C, Bastien A, List JF, Fiedorek FT. 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. https://doi.org/10.2337/dc09-0517
  16. 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. https://doi.org/10.1111/dom.12054
  17. Cefalu WT, Leiter LA, Yoon KH, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATASU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 2013;382:941-950. https://doi.org/10.1016/S0140-6736(13)60683-2
  18. 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. https://doi.org/10.2337/dc12-2491
  19. 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. https://doi.org/10.1111/dom.12090

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