Dapagliflozin: A review of its use in type 2 diabetes mellitus

Drugs

Volumn 72, Issue 17, 2012, Pages 2289-2312

  Plosker, Greg L ^a  

^a ADIS INTERNATIONAL LIMITED   (New Zealand)

Author keywords

Adis Drug Evaluations; Dapagliflozin; Pharmacokinetics; Pharmacology; Type 2 diabetes mellitus

Indexed keywords

DAPAGLIFLOZIN; DIGOXIN; FORXIGA; GLIMEPIRIDE; GLIPIZIDE; GLYCOSYLATED HEMOGLOBIN; INSULIN; METFORMIN; PIOGLITAZONE; PLACEBO; ROSIGLITAZONE; SIMVASTATIN; SITAGLIPTIN; SULFONYLUREA; UNCLASSIFIED DRUG; VALSARTAN; WARFARIN;

ADD ON THERAPY; ARTHRALGIA; BACKACHE; BRONCHITIS; COUGHING; DIARRHEA; DRUG BIOAVAILABILITY; DRUG ELIMINATION; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; EMBASE; EVENING DOSAGE; FAINTNESS; GENITAL TRACT INFECTION; GLUCOSE ABSORPTION; GLUCOSE BLOOD LEVEL; GLUCOSE URINE LEVEL; GLUCOSURIA; GLYCEMIC CONTROL; HEADACHE; HEMOGLOBIN BLOOD LEVEL; HUMAN; HYPERTENSION; HYPOGLYCEMIA; HYPOTENSION; HYPOVOLEMIA; INFLUENZA; INSULIN RELEASE; KIDNEY FAILURE; LONG TERM CARE; MEDICAL LITERATURE; MEDLINE; NON INSULIN DEPENDENT DIABETES MELLITUS; PHASE 3 CLINICAL TRIAL (TOPIC); PLASMA HALF LIFE; PUBLICATION; PUBLISHING; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RHINOPHARYNGITIS; SIDE EFFECT; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; WEIGHT REDUCTION;

DIABETES MELLITUS, TYPE 2; DRUG THERAPY, COMBINATION; GLIPIZIDE; GLUCOSIDES; HUMANS; HYPOGLYCEMIC AGENTS; METFORMIN; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SODIUM-GLUCOSE TRANSPORT PROTEINS; TREATMENT OUTCOME;

EID: 84869998632     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.2165/11209910-000000000-00000     Document Type: Review

References (84)

1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012 Jun; 35 (6): 1364-79
2. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2012; 35 Suppl 1: S64-71
3. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2012; 35 Suppl. 1: S11-63
4. International Diabetes Federation. Global diabetes plan 2011-2021 [online]. Available from URL: www.idf.org/sites/default/files/Global-Diabetes- Plan-Final.pdf [Accessed 2012 Jul 13]
5. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010 Jan; 87 (1): 4-14
6. Roglic G, Unwin N. Mortality attributable to diabetes: estimates for the year 2010. Diabetes Res Clin Pract 2010 Jan; 87 (1): 15-9
7. U.K. Prospective Diabetes Study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes 1995 Nov; 44 (11): 1249-58
8. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000 Aug 12; 321 (7258): 405-12
9. Moss SE, Klein R, Klein BE, et al. The association of glycemia and cause-specific mortality in a diabetic population. Arch Intern Med 1994 Nov 14; 154 (21): 2473-9
10. Turner RC, Cull CA, Frighi V, et al. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS)Group. JAMA1999 Jun 2; 281 (21): 2005-12
11. Resnick HE, Foster GL, Bardsley J, et al. Achievement of American Diabetes Association clinical practice recommendations among U.S. adults with diabetes, 1999-2002: the National Health and Nutrition Examination Survey. Diabetes Care 2006 Mar; 29 (3): 531-7
12. Ong KL, Cheung BM, Wong LY, et al. Prevalence, treatment, and control of diagnosed diabetes in the U.S. National Health and Nutrition Examination Survey 1999-2004. Ann Epidemiol 2008 Mar; 18 (3): 222-9
13. Neumiller JJ, White JR, Campbell RK. Sodium glucose cotransport inhibitors: progress and therapeutic potential in type 2 diabetes mellitus. Drugs 2010; 70: 377-85
14. Nair S, Wilding JP. Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab 2010 Jan; 95 (1): 34-42
15. Dapagliflozin (Forxiga): EU summary of product characteristics [online]. Available from URL: http://www.medi cines.org.uk/emc/medicine/27188/SPC/ Forxiga+5mg++%26+ 10+mg+film+coated+tablets/[Accessed 2012 Nov 19]
16. AstraZeneca. Forxiga (dapagliflozin) now approved in European Union for treatment of type 2 diabetes [media release]. 2012 Nov 14 [online]. Available from URL: http://www.astrazeneca.com/Media/Press-releases/Article/20121 114-forxiga-eu-Approval-type-2-diabetes [Accessed 2012 Nov 19]
17. Wright EM, Loo DD, Hirayama BA, et al. Surprising versatility of Na+-glucose cotransporters: SLC5. Physiology (Bethesda) 2004 Dec; 19: 370-6
18. Meng W, Ellsworth BA, Nirschl AA, et al. Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem 2008 13 Mar; 51 (5): 1145-9
19. 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 Jan; 93 (1): 397-404
20. Idris I, Donnelly R. Sodium-glucose co-transporter-2 inhibitors: an emerging new class of oral antidiabetic drug. Diabetes Obes Metab 2009 Feb; 11 (2): 79-88
21. Bakris GL, Fonseca VA, Sharma K, et al. Renal sodiumglucose transport: role in diabetes mellitus and potential clinical implications. Kidney Int 2009 Jun; 75 (12): 1272-7
22. Scheepers A, Joost HG, Schurmann A. The glucose transporter families SGLT and GLUT: molecular basis of normal and aberrant function. J Parenter Enteral Nutr 2004 Sep-Oct; 28 (5): 364-71
23. Bellamine A, Uveges A, Thompson C, et al. Dapagliflozin selectively inhibits human SGLT2 versus SGLT1, SMIT, SGLT4 and SGLT6 [abstract no. 987-P]. Diabetes 2011; 60: A271
24. Komoroski B, Vachharajani N, Boulton D, et al. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Ther 2009 May; 85 (5): 520-6
25. Komoroski B, Vachharajani N, Feng Y, et al. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin Pharmacol Ther 2009 May; 85 (5): 513-9
26. List JF, Woo V, Morales E, et al. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 2009 April; 32 (4): 650-7
27. DeFronza RA, Hompesch M, Kasichayanula S, et al. Dapagliflozin reduces renal threshold for glucose excretion in type 2 diabetes [abstract no. 747]. Diabetologia 2012; 55 Suppl. 1: S306
28. Obermeier MT, Yao M, Khanna A, et al. In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans. Drug Metab Dispos 2010 March; 38 (3): 405-14
29. Kasichayanula S, Liu X, Zhang W, et al. Effect of a high-fat meal on the pharmacokinetics of dapagliflozin, a selective SGLT2 inhibitor, in healthy subjects. Diabetes Obes Metab 2011 August; 13 (8): 770-3
30. Kasichayanula S, Liu X, Zhang W, et al. Influence of hepatic impairment on the pharmacokinetics and safety profile of dapagliflozin: an open-label, parallel-group, single-dose study. Clin Ther 2011 Nov; 33 (11): 1798-808
31. Kasichayanula S, Chang M, Hasegawa M, et al. Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus. Diabetes Obes Metab 2011 April; 13 (4): 357-65
32. Kasichayanula S, Liu X, Hesney M, et al. Meta analysis of dapagliflozin pharmacokinetics and dose/exposureurinary glucose pharmacodynamic relationships [abstract no. PIII-99]. Clin Pharmacol Ther 2012; 91: S131-S2
33. Hong Y, Roy A, Boulton D, et al. Population pharmacokinetic analysis of dapagliflozin in patients with type 2 diabetes mellitus [abstract]. Clin Pharmacol Ther 2012; 91: S43
34. Kasichayanula S, Liu X, Shyu WC, et al. Lack of pharmacokinetic interaction between dapagliflozin, a novel sodium-glucose transporter 2 inhibitor, and metformin, pioglitazone, glimepiride or sitagliptin in healthy subjects. Diabetes Obes Metab 2011 Jan; 13 (1): 47-54
35. Kasichayanula S, Liu X, Griffen SC, et al. Effects of rifampin and mefenamic acid on the pharmacokinetics and pharmacodynamics of dapagliflozin. Diabetes Obes Metab. Epub 2012 Oct 15
36. Kasichayanula S, Chang M, Liu X, et al. Lack of pharmacokinetic interactions between dapagliflozin and simvastatin, valsartan, warfarin, or digoxin. Adv Ther 2012 Feb; 29 (2): 163-77
37. 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 Oct; 33 (10): 2217-24
38. 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 randomised, doubleblind, placebo-controlled trial. Lancet 2010; 375 (9733): 2223-33
39. Rosenstock J, Vico M, Wei L, et al. Effects of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, on hemoglobin A1c, body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care 2012 July; 35 (7): 1473-8
40. 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 Oct; 13 (10): 928-38
41. Wilding JPH, 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 Mar 20; 156 (6): 405-15
42. 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, activecontrolled noninferiority trial. Diabetes Care 2011 Sep; 34 (9): 2015-22
43. Wilding JPH, 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 Sep; 32 (9): 1656-62
44. Henry RR, Murray AV, Marmolejo MH, et al. Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial. Int J Clin Pract 2012 May; 66 (5): 446-56
45. Zhang L, Feng Y, List J, et al. Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight. Diabetes Obes Metab 2010 Jun; 12 (6): 510-6
46. Bolinder J, Ljunggren O, Kullberg J, et al. 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 Mar; 97 (3): 1020-31
47. 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 Oct; 14 (10): 951-9
48. Hardy E, Salsali A, Wessman C, et al. Exploration of the relationship of reduction in HbA1c and body weight by dapagliflozin in patients with T2DM: pooled analysis of 5 clinical trials [abstract no. 987-P]. 72nd Annual Meeting of the American Diabetes Association; 2012 Jun 8-12; Philadelphia (PA
49. White JR, Bastien A, Parikh S, et al. Dapagliflozin monotherapy and combination therapy reduces hyperglycemia in patients with type 2 diabetes [abstract no. 96E]. Pharmacotherapy 2011; 31 (10): 337e
50. Langkilde AM, Sugg J, Johannson P, et al. A meta-Analysis of cardiovascular outcomes in clinical trials of dapagliflozin [abstract no. A8947]. Circulation 2011 Nov; 124 (21 Suppl. 1
51. Hardy E, Salsali A, Hruba V, et al. Efficacy increases with increasing baseline HbA1c category with dapagliflozin therapy [abstract no. 82-OR]. 72nd Annual Meeting of the American Diabetes Association; 2012 Jun 8-12; Philadelphia (PA
52. Hardy E, Rohwedder K, Hruba V, et al. Dapagliflozin, a selective SGLT2 inhibitor, reduces serum levels of uric acid in patients with type 2 diabetes [abstract no. 843]. Diabetologia 2011; 54: S344-S5
53. Wilding JP, Woo VC, Rohwedder K, et al. Long-term effectiveness of dapagliflozin over 104 weeks in patients with type 2 diabetes poorly controlled with insulin [abstract no. 1042-P]. 72nd Annual Meeting of the American Diabetes Association; 2012 Jun 8-12; Philadelphia (PA
54. Salsali A, Rohwedder K, Mansfield TA, et al. Durability of dapagliflozin treatment response in patients with T2DM: 2-year results [abstract no. 1030-P]. 72nd Annual Meeting of the American Diabetes Association; 2012 Jun 8-12; Philadelphia (PA
55. Woo V, Tang W, Salsali A. Long-term efficacy of dapagliflozin monotherapy in patients with type 2 diabetes mellitus [abstract no. D-0991]. 21st World Diabetes Congress; 2011 Dec 4-8; Dubai
56. Langkilde AM, Sugg J, Parikh S. Dapagliflozin, a novel antihyperglycemic agent that promotes urinary glucose excretion, reduces systolic blood pressure in patients with type 2 diabetes mellitus [abstract no. 9520]. 84th Annual Scientific Sessions of the American Heart Association; 2011 Nov 12-16; Orlando (FL
57. Bailey CJ, Gross JL, Yadav M, et al. Long-term efficacy of dapagliflozin as add-on to metformin (MET) in T2DM inadequately controlled with MET alone [abstract no. 988-P]. Diabetes 2011; 60: A271
58. Bailey CJ, Gross JL, Yadav M, et al. Sustained efficacy of dapagliflozin when added to metformin in type 2 diabetes inadequately controlled by metformin monotherapy [abstract no. 146]. Diabetologia 2011; 54: S67
59. Del Prato S, Nauck MA, Rohwedder K, et al. Long-term efficacy and safety of add-on dapagliflozin vs add-on glipizide in patients with type 2 diabetes mellitus inadequately controlled with metformin: 2-year results [abstract no. 852]. Diabetologia 2011; 54: S348
60. Langkilde A, Rhwedder K, Iqbal N, et al. Measures of betacell function and insulin sensitivity over time in patients with type 2 diabetes receiving dapagliflozin versus glifizide as add-on therapy to metformin [abstract no. 750]. European Association for the Study of Diabetes; 2012 Oct 1-5; Berlin
61. Jabbour S, Hardy E, Sugg J, et al. Dapagliflozin as add-on therapy to sitagliptin with or without metformin: a randomized, double-blind, placebo-controlled study [abstract no. 1071-P]. 72nd Annual Meeting of the American Diabetes Association; 2012 Jun 8-12; Philadelphia (PA
62. Leiter LA, Cefalu WT, Debruin TW, et al. Efficacy and safety of dapagliflozin for type 2 diabetes mellitus patients with a history of cardiovascular disease [abstract no. 1114-P]. 72nd Annual Meeting of the American Diabetes Association; 2012 Jun 8-12; Philadelphia (PA
63. Cefalu WT, Leiter LA, Debruin TW, et al. Dapagliflozin treatment for type 2 diabetes mellitus patients with comorbid cardiovascular disease and hypertension [abstract no. 1056-P]. 72nd Annual Meeting of the American Diabetes Association; 2012 Jun 8-12; Philadelphia (PA
64. Kaku K, Inoue S, Matsuoka O, et al. Efficacy and safety of dapagliflozin as monotherapy for type 2 diabetes mellitus in Japanese patients [abstract no. 1014-P]. 72nd Annual Meeting of the American Diabetes Association; 2012 Jun 8-12; Philadelphia (PA
65. Salsali A, Wei L, Wessman C, et al. Dapagliflozin improves glycemic control and reduces body weight in patients with T2DM across the treatment continuum [abstract no. 2353-PO]. 72nd Annual Meeting of the American Diabetes Association; 2012 Jun 8-12; Philadelphia (PA
66. Wygant GD, Chalamandaris A-G, Iloeje UH, et al. Dapagliflozin is more effective than glipizide in achieving the composite outcome of glycemic control, weight reduction, and lack of hypoglycemia [abstract no. 2397-PO]. 72nd Annual Meeting of the American Diabetes Association; 2012 Jun 8-12; Philadelphia (PA
67. Grandy S, Langkilde A, Ingelgard A, et al. Quality of life (EQ-5D) among type 2 diabetes mellitus patients treated with dapagliflozin for 24 weeks [abstract no. 2382-PO]. 72nd Annual Meeting of the American Diabetes Association; 2012 Jun 8-12; Philadelphia (PA
68. Bolinder J, Ljunggren O, Johansson L, et al. Dapagliflozin produces long-term reductions in body weight, waist circumference and total fat mass in patients with type 2 diabetes inadequately controlled on metformin [abstract no. 751]. European Association for the Study of Diabetes; 2012 Oct 1-5; Berlin
69. Bailey CJ, Wilding J, Nauck MA. Sustained reductions in weight and HbA1c with dapagliflozin: long-term results from phase III clinical studies in type 2 diabetes [abstract no. 721]. European Association for the Study of Diabetes; 2012 Oct 1-5; Berlin
70. Bolinder J, Ljunggren O, Kullberg J, et al. 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 Mar; 97 (3): 1020-31
71. Johnsson K, Ptaszynska A, Apanovitch A, et al. Safety of dapagliflozin in clinical trials for type 2 diabetes mellitus [abstract no. 743 plus poster]. European Association for the Study of Diabetes; 2012 Oct 1-5; Berlin
72. Basile J, Ptasynska A, Ying L, et al. The effects of dapagliflozin on cardiovascular risk factors in patients with type 2 diabetes mellitus [abstract no. A59]. Circ Cardiovasc Qual Outcomes 2012 Jul; 5 (1003
73. Carlson GF, Tou CKP, Parikh S, et al. Evaluation of the effect of dapagliflozin on cardiac repolarization: a thorough QT/QTc study. Diabetes Therapy 2011 Sep; 2 (3): 123-32
74. Ptaszynska A, Chalamandaris A-G, Sugg J, et al. Dapagliflozin does not impact renal function in patients with type 2 diabetes [abstract no. 242]. European Association for the Study of Diabetes; 2012 Oct 1-5; Berlin
75. Kohan D, Fioretto P, List J, et al. Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment [abstract no. TH-PO524]. J Am Soc Nephrol 2011; 22: 232A
76. Ljunggren O, Bolinder J, Johansson L, et al. Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin. Diabetes Obes Metab 2012 May 31; 14 (11): 990-9
77. Ljunggren O, Bolinder J, Johansson L, et al. Dapagliflozin has no long-term effect on markers of bone turnover or bone mineral density in patients with inadequately controlled type 2 diabetes on metformin [abstract no. 748]. European Association for the Study of Diabetes; 2012 Oct 1-5; Berlin
78. Ptaszynska A, Johnsson KM, Apanovitch AM, et al. Safety of dapagliflozin in clinical trials for T2DM [abstract no. 1011-P]. 72nd Annual Meeting of the American Diabetes Association; 2012 Jun 8-12; Philadelphia (PA
79. European Medicines Agency. European Medicines Agency recommends authorisation of novel treatment for type 2 diabetes: SGLT2 transporter protein inhibitor improves glycaemic control in adult patients with type 2 diabetes mellitus [media release]. 2012 Apr 20 [online]. Available from URL: http://www.ema.europa.eu/docs/en-GB/docu ment-library/Press-release/2012/04/ WC500125707.pdf [Accessed 2012 Jun 7]
80. European Medicines Agency. Summary of opinion (initial authorisation): Forxiga (dapagliflozin) [online]. Available from URL: http://www.ema.europa.eu/ docs/en-GB/docu ment-library/Summary-of-opinion-Initial-Authorisation/human/ 002322/WC500125684.pdf [Accessed 2012 Jun 7]
81. European Medicines Agency. Human medicines: Forxiga [online]. Available from URL: http://www.ema.europa.eu/ema/[Accessed 2012 Jun 7]
82. Tahrani AA, Bailey CJ, Del Prato S, et al. Management of type 2 diabetes: new and future developments in treatment. Lancet 2011 Jul 9; 378: 182-97
83. AstraZeneca Global. AstraZeneca and Bristol-Myers Squibb receive complete response letter from US Food and Drug Administration for dapagliflozin [media release]. 2012 Jan 19 [online]. Available from URL: http://www. astrazeneca.com/Media/Press-releases/Article/19012012-AstraZeneca-Bristol-Myers- Squibb-receive-CRL-for-dapag liflozin/[Accessed 2012 August 16]
84. SGLT2 inhibitors under spotlight at US diabetes meeting [media release]. 2012 Jun 12 [online]. Available from URL: http://www.pharmatimes.com/article/12- 06-12/SGLT2-inhi bitors-under-spotlight-At-US-diabetes-meeting.aspx [Accessed 2012 August 16]