A Novel therapeutic agent for type 2 diabetes mellitus: SGLT2 inhibitor

Diabetes and Metabolism Journal

Volumn 38, Issue 4, 2014, Pages 261-273

  Jung, Chang Hee ^a   Jang, Jung Eun ^a   Park, Joong Yeol ^a  

^a University of Ulsan College of Medicine   (South Korea)

Author keywords

Canagliflozin; Dapagliflozin; Diabetes mellitus, type 2; Glucosuria; SGLT2 inhibitor

Indexed keywords

CANAGLIFLOZIN; DAPAGLIFLOZIN; EMPAGLIFLOZIN; ERTUGLIFLOZIN; GLIMEPIRIDE; GLIPIZIDE; GLUCOSE; HEMOGLOBIN A1C; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; IPRAGLIFLOZIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LUSEOGLIFLOZIN; METFORMIN; ORAL ANTIDIABETIC AGENT; PHLORIZIN; PIOGLITAZONE; PLACEBO; SITAGLIPTIN; SODIUM GLUCOSE COTRANSPORTER 1; SODIUM GLUCOSE COTRANSPORTER 2; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; SULFONYLUREA; TOFOGLIFLOZIN;

ADD ON THERAPY; ANTIDIABETIC ACTIVITY; BLADDER CANCER; BREAST CANCER; CHOLESTEROL BLOOD LEVEL; CONTROLLED CLINICAL TRIAL (TOPIC); DEHYDRATION; DIARRHEA; DIET THERAPY; DRUG ABSORPTION; DRUG APPROVAL; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG SAFETY; DRUG SELECTIVITY; ELECTROLYTE DISTURBANCE; EXERCISE; FEVER; FOOD AND DRUG ADMINISTRATION; GENITAL TRACT INFECTION; GLOMERULUS FILTRATION; GLUCOSE HOMEOSTASIS; GLUCOSE TRANSPORT; GLUCOSURIA; GLYCEMIC CONTROL; HUMAN; HYPERKALEMIA; HYPOGLYCEMIA; HYPOTENSION; HYPOVOLEMIA; INHIBITION KINETICS; KIDNEY DYSFUNCTION; KIDNEY FUNCTION; KIDNEY TUBULE ABSORPTION; MALABSORPTION; MALARIA; MEDICAL DECISION MAKING; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; ORTHOSTATIC HYPOTENSION; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POLLAKISURIA; POLYURIA; POSITIONAL DIZZINESS; POSTMARKETING SURVEILLANCE; POSTPRANDIAL STATE; REVIEW; SIDE EFFECT; TREATMENT OUTCOME; URINARY TRACT INFECTION; WEIGHT REDUCTION;

EID: 84906923912     PISSN: 22336079     EISSN: 22336087     Source Type: Journal    
DOI: 10.4093/dmj.2014.38.4.261     Document Type: Review

References (74)

1. Guariguata L. By the numbers: new estimates from the IDF Diabetes Atlas Update for 2012. Diabetes Res Clin Pract 2012;98: 524-5.
2. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352: 837-53.
3. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-89.
4. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002;287:360-72.
5. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129-39.
6. Action to Control Cardiovascular Risk in Diabetes Study G, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-59.
7. Chao EC, Henry RR. SGLT2 inhibition: a novel strategy for diabetes treatment. Nat Rev Drug Discov 2010;9:551-9.
8. Hasan FM, Alsahli M, Gerich JE. SGLT2 inhibitors in the treatment of type 2 diabetes. Diabetes Res Clin Pract 2014;104: 297-322.
9. Raskin P. Sodium-glucose cotransporter inhibition: therapeutic potential for the treatment of type 2 diabetes mellitus. Diabetes Metab Res Rev 2013;29:347-56.
10. Mather A, Pollock C. Glucose handling by the kidney. Kidney Int Suppl 2011;(120):S1-6.
11. Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet Med 2010;27:136-42.
12. Abdul-Ghani MA, Norton L, Defronzo RA. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr Rev 2011;32:515-31.
13. Wright EM, Hirayama BA, Loo DF. Active sugar transport in health and disease. J Intern Med 2007;261:32-43.
14. Bays H. From victim to ally: the kidney as an emerging target for the treatment of diabetes mellitus. Curr Med Res Opin 2009;25:671-81.
15. Gerich JE, Meyer C, Woerle HJ, Stumvoll M. Renal gluconeogenesis: its importance in human glucose homeostasis. Diabetes Care 2001;24:382-91.
16. 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;54:3427-34.
17. Kamran M, Peterson RG, Dominguez JH. Overexpression of GLUT2 gene in renal proximal tubules of diabetic Zucker rats. J Am Soc Nephrol 1997;8:943-8.
18. Mogensen CE. Maximum tubular reabsorption capacity for glucose and renal hemodynamcis during rapid hypertonic glucose infusion in normal and diabetic subjects. Scand J Clin Lab Invest 1971;28:101-9.
19. Freitas HS, Anhe GF, Melo KF, Okamoto MM, Oliveira-Souza M, Bordin S, Machado UF. 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;149:717-24.
20. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009;58:773-95.
21. DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab 2012;14:5-14.
22. Ehrenkranz JR, Lewis NG, Kahn CR, Roth J. Phlorizin: a review. Diabetes Metab Res Rev 2005;21:31-8.
23. Alvarado F, Crane RK. Phlorizin as a competitive inhibitor of the active transport of sugars by hamster small intestine, in vitro. Biochim Biophys Acta 1962;56:170-2.
24. Rossetti L, Smith D, Shulman GI, Papachristou D, DeFronzo RA. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest 1987; 79:1510-5.
25. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev 2011;91:733-94.
26. Thorens B, Mueckler M. Glucose transporters in the 21st Century. Am J Physiol Endocrinol Metab 2010;298:E141-5.
27. Elsas LJ, Rosenberg LE. Familial renal glycosuria: a genetic reappraisal of hexose transport by kidney and intestine. J Clin Invest 1969;48:1845-54.
28. Plosker GL. Dapagliflozin: a review of its use in type 2 diabetes mellitus. Drugs 2012;72:2289-312.
29. European Medicines Agency: European Medicines Agency authorizing the use of dapagliflozin in November 2012. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002322/human_med_001546.jsp&mid=WC0b01ac058001d124 (updated 2014 Jul 16).
30. U.S. Food and Drug Administration: FDA approves Farxiga to treat type 2 diabetes. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm380829.htm (updated 2014 Jan 9).
31. Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. 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: 2217-24.
32. 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;375:2223-33.
33. Strojek K, Yoon KH, Hruba V, Elze M, Langkilde AM, Parikh S. 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;13:928-38.
34. Rosenstock J, Vico M, Wei L, Salsali A, List JF. 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: 1473-8.
35. Wilding JP, Woo V, Soler NG, Pahor A, Sugg J, Rohwedder K, Parikh S; Dapagliflozin 006 Study Group. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med 2012; 156:405-15.
36. Wilding JP, Woo V, Rohwedder K, Sugg J, Parikh S; for the Dapagliflozin 006 Study Group. Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years. Diabetes Obes Metab. Epub 2013 Aug 1. DOI: http://dx.doi.org/10.1111/dom.12187.
37. Bolinder J, Ljunggren O, Kullberg J, Johansson L, Wilding J, Langkilde AM, Sugg J, Parikh S. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 2012;97:1020-31.
38. Henry RR, Murray AV, Marmolejo MH, Hennicken D, Ptaszynska A, List JF. Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial. Int J Clin Pract 2012;66:446-56.
39. Nauck MA, Del Prato S, Meier JJ, Duran-Garcia S, Rohwedder K, Elze M, Parikh SJ. 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;34:2015-22.
40. U.S. Food and Drug Administration: FDA approves Invokana to treat type 2 diabetes. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm345848.htm (updated 2013 Mar 29).
41. European Medicines Agency: European Medicines Agency authorizing the use of canagliflozin in November 2013. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002649/human_med_001707.jsp&mid=WC0b01ac058001d124 (updated 2013 Nov 30).
42. Stenlof K, Cefalu WT, Kim KA, Alba M, Usiskin K, Tong C, Canovatchel W, Meininger G. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab 2013;15:372-82.
43. Wilding JP, Charpentier G, Hollander P, Gonzalez-Galvez G, Mathieu C, Vercruysse F, Usiskin K, Law G, Black S, Canovatchel W, Meininger G. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: a randomised trial. Int J Clin Pract 2013;67:1267-82.
44. Cefalu WT, Leiter LA, Yoon KH, Arias P, Niskanen L, Xie J, Balis DA, Canovatchel W, Meininger G. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 2013;382:941-50.
45. Schernthaner G, Gross JL, Rosenstock J, Guarisco M, Fu M, Yee J, Kawaguchi M, Canovatchel W, Meininger G. Canagliflozin compared with sitagliptin for patients with type 2 dia betes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care 2013;36:2508-15.
46. Forst T, Guthrie R, Goldenberg R, Yee J, Vijapurkar U, Meininger G, Stein P. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone. Diabetes Obes Metab 2014;16:467-77.
47. Polidori D, Sha S, Mudaliar S, Ciaraldi TP, Ghosh A, Vaccaro N, Farrell K, Rothenberg P, Henry RR. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care 2013;36:2154-61.
48. Lavalle-Gonzalez FJ, Januszewicz A, Davidson J, Tong C, Qiu R, Canovatchel W, Meininger G. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia 2013;56:2582-92.
49. Devineni D, Morrow L, Hompesch M, Skee D, Vandebosch A, Murphy J, Ways K, Schwartz S. Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin. Diabetes Obes Metab 2012;14: 539-45.
50. Liakos A, Karagiannis T, Athanasiadou E, Sarigianni M, Mainou M, Papatheodorou K, Bekiari E, Tsapas A. Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab. Epub 2014 Apr 26. DOI: http://dx.doi.org/10.1111/dom.12307.
51. Poole RM, Dungo RT. Ipragliflozin: first global approval. Drugs 2014;74:611-7.
52. Pafili K, Papanas N. Tofogliflozin: the road goes ever on. Expert Opin Pharmacother 2014;15:1197-201.
53. Seino Y, Sasaki T, Fukatsu A, Ubukata M, Sakai S, Samukawa Y. Efficacy and safety of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, phase 3 study. Curr Med Res Opin 2014.
54. Miao Z, Nucci G, Amin N, Sharma R, Mascitti V, Tugnait M, Vaz AD, Callegari E, Kalgutkar AS. Pharmacokinetics, metabolism, and excretion of the antidiabetic agent ertugliflozin (PF-04971729) in healthy male subjects. Drug Metab Dispos 2013; 41:445-56.
55. Johnsson KM, Ptaszynska A, Schmitz B, Sugg J, Parikh SJ, List JF. Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin. J Diabetes Complications 2013;27:479-84.
56. Johnsson KM, Ptaszynska A, Schmitz B, Sugg J, Parikh SJ, List JF. Urinary tract infections in patients with diabetes treated with dapagliflozin. J Diabetes Complications 2013;27:473-8.
57. Nyirjesy P, Sobel JD, Fung A, Mayer C, Capuano G, Ways K, Usiskin K. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. Curr Med Res Opin 2014;30:1109-19.
58. Nicolle LE, Capuano G, Fung A, Usiskin K. Urinary tract infection in randomized phase III studies of canagliflozin, a sodium glucose co-transporter 2 inhibitor. Postgrad Med 2014;126: 7-17.
59. Nair S, Wilding JP. Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab 2010;95:34-42.
60. 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;32:1656-62.
61. Zhang L, Feng Y, List J, Kasichayanula S, Pfister M. Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight. Diabetes Obes Metab 2010;12:510-6.
62. Ptaszynska A, Chalamandaris AG, Sugg JE, Johnsson KM, Parikh S, List JL. Effect of dapagliflozin on renal function. Diabetes 2012;61(Suppl 1):A283.
63. Kohan DE, Fioretto P, Tang W, List JF. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int 2014;85: 962-71.
64. Rosenstock J, Aggarwal N, Polidori D, Zhao Y, Arbit D, Usiskin K, Capuano G, Canovatchel W; Canagliflozin DIA 2001 Study Group. 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;35:1232-8.
65. Yale JF, Bakris G, Cariou B, Yue D, David-Neto E, Xi L, Figueroa K, Wajs E, Usiskin K, Meininger G. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab 2013;15:463-73.
66. Janssen Research and Development LCC: Canagliflozin slides presented at the Food and Drug Administration (FDA) Endo crinologic and Metabolic Drugs Advisory Committee (EMDAC) meeting, January 10, 2013. Available from: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/ucm336233.htm (updated 2013 Jan 18).
67. Ptaszynska A, Hardy E, Johnsson E, Parikh S, List J. Effects of dapagliflozin on cardiovascular risk factors. Postgrad Med 2013;125:181-9.
68. Burki TK. FDA rejects novel diabetes drug over safety fears. Lancet 2012;379:507.
69. Ptaszynska A, Johnsson KM, Apanovitch AM. Safety of dapagliflozin in clinical trials for T2DM. Diabetes 2012;61(Suppl 1):A258.
70. FORXIGA: Summary of product characteristics. Wilmington: Bristol-Myers Squibb/AstraZeneca EEIG; 2013.
71. AstraZeneca Global: AstraZeneca and Bristol-Myers Squibb receive complete response letter from US Food and Drug Administration for dapagliflozin. Available from: http://www.astrazeneca.com/Media/Press-releases/Article/19012012--AstraZeneca-Bristol-Myers-Squibb-receive-CRL-for-dapagliflozin (updated 2012 Jan 19).
72. Ghosh RK, Ghosh SM, Chawla S, Jasdanwala SA. SGLT2 inhibitors: a new emerging therapeutic class in the treatment of type 2 diabetes mellitus. J Clin Pharmacol 2012;52:457-63.
73. Devenny JJ, Godonis HE, Harvey SJ, Rooney S, Cullen MJ, Pelleymounter MA. Weight loss induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats. Obesity (Silver Spring) 2012;20: 1645-52.
74. Misra M. SGLT2 inhibitors: a promising new therapeutic option for treatment of type 2 diabetes mellitus. J Pharm Pharmacol 2013;65:317-27.