Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes

Expert Opinion on Drug Metabolism and Toxicology

Volumn 11, Issue 1, 2015, Pages 125-137

  Maranghi, Marianna ^a   Carnovale, Anna ^a   Durante, Cosimo ^a   Tarquini, Giovanna ^a   Tiseo, Giusy ^a   Filetti, Sebastiano ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Dapagliflozin; Kidney; SGLT2 inhibitors; Type 2 diabetes

Indexed keywords

DAPAGLIFLOZIN; 2-(3-(4-ETHOXYBENZYL)-4-CHLOROPHENYL)-6-HYDROXYMETHYLTETRAHYDRO-2H-PYRAN-3,4,5-TRIOL; ANTIDIABETIC AGENT; BENZHYDRYL DERIVATIVE; GLUCOSIDE; SODIUM GLUCOSE COTRANSPORTER;

BLADDER CANCER; DATA BASE; DRUG EFFICACY; DRUG INTERACTION; DRUG METABOLISM; DRUG SAFETY; FOOD AND DRUG ADMINISTRATION; GENITAL TRACT INFECTION; GLUCOTOXICITY; HUMAN; METABOLIC REGULATION; NON INSULIN DEPENDENT DIABETES MELLITUS; PHARMACODYNAMICS; PHARMACOKINETICS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); REVIEW; RISK FACTOR; TREATMENT OUTCOME; URINARY TRACT INFECTION; ANIMAL; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL (TOPIC); DIABETES MELLITUS, TYPE 2; METABOLISM; PROCEDURES;

ANIMALS; BENZHYDRYL COMPOUNDS; CLINICAL TRIALS AS TOPIC; DIABETES MELLITUS, TYPE 2; GLUCOSIDES; HUMANS; HYPOGLYCEMIC AGENTS; SODIUM-GLUCOSE TRANSPORT PROTEINS; TREATMENT OUTCOME;

EID: 84918502268     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2015.986457     Document Type: Review

References (68)

1. Epidemiology and prevention of diabetes. IDF (International Diabetes Federation) Diabetes Atlas sixth edition. Available from: www.idf.org/diabetesatlas/introduction [Last accessed 6 September 2014]
2. Kalyani RR, Egan JM. Diabetes and altered glucose metabolism with aging. Endocrinol Metab Clin North Am 2013;42(2):333-47
3. Forbes JM, Cooper ME. Mechanisms of diabetic complications physiological. Physiol Rev 2013;93(1):137-88
4. Zhuo X, Zhang P, Hoerger TJ. Lifetime direct medical costs of treating type 2 diabetes and diabetic complications. Am J Prev Med 2013;45(3):253-61
5. Lorber D. Importance of cardiovascular disease risk management in patients with type 2 diabetes mellitus. Diabetes Metab Syndr Obes 2014;7:169-83
6. Centers for Disease Control and Prevention. National diabetes fact sheet: National estimates and general information on diabetes and prediabetes in the United States. US Department of Health and Human Services, Centers for Disease Control and Prevention; Atlanta: 2011
7. Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet 2014;383:1068-83
8. Lewis GF, Carpentier A, Adeli K, et al. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 2002;23(2):201-29
9. De Fronzo RA. The triumvirate: betacell, muscle, liver. A collusion responsible for NIDDM. Diabetes 1988;37:667-87
10. Toft-Nielsen MB, Damholt MB, Madsbad S, et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001;86:3717-23
11. Dunning BE, Gerich JE. The role of alpha-cell dysregulation in fasting and postprandial hyperglycemia in type 2 diabetes and therapeutic implications. Endocr Rev 2007;28(3):253-83
12. Wilding JP. The role of the kidneys in glucose homeostasis in type 2 diabetes: clinical implications and therapeutic significance through sodium glucose cotransporter 2 inhibitors. Metabolism 2014;63(10):1228-37
13. Stolar MW, Hoogwerf BJ, Gorshow SM, et al. Managing type 2 diabetes: going beyond glycemic control. J Manag Care Pharm 2008;14(5 Suppl B):s2-19
14. FDA guidance for industry, diabetes mellitus-evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. 2008. Available from: http://www.fda. gov/downloads/Drugs/GuidanceComplianceRegulatory Information/Guidances/ucm071627.pdf [Last accessed 6 September 2014] .
15. American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care 2014;37(Suppl 1):S14-80
16. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia 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). Diabetologia 2012;55(6):1577-96
17. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev 2011;91(2):733-94
18. Wood IS, Trayhurn P. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 2003;89(1):3-9
19. Rosenwasser RF, Sultan S, Sutton D, et al. SGLT-2 inhibitors and their potential in the treatment of diabetes. Diabetes Metab Syndr Obes 2013;27:453-67
20. 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(2):105-12
21. Marks J, Carvou NJ, Debnam ES, et al. Diabetes increases facilitative glucose uptake and GLUT2 expression at the rat proximal tubule brush border membrane. J Physiol 2003;553(Pt 1):137-45.
22. Tabatabai NM, Sharma M, Blumenthal SS, Petering DH. Enhanced expressions of sodium-glucose cotransporters in the kidneys of diabetic Zucker rats. Diabetes Res Clin Pract 2009;83(1):e27-30.
23. Merovci A, Solis-Herrera C, Daniele G, et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest 2014;124(2):509-14.
24. Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodiumglucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest 2014;124(2):499-508.
25. Rossetti L, Smith D, Shulman GI, et al. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest 1987;79(5):1510-15.
26. Rossetti L, Shulman GI, Zawalich W, DeFronzo RA. Effect of chronic hyperglycemia on in vivo insulin secretion in partially pancreatectomized rats. J Clin Invest 1987;80(4):1037-44
27. Oku A, Ueta K, Arakawa K, et al. T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes 1999;48(9):1794-800
28. Whaley JM, Tirmenstein M, Reilly TP, et al. Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus. Diabetes Metab Syndr Obes 2012;5:135-48
29. 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
30. Nauck MA. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes. Drug Des Devel Ther 2014;8:1335-80
31. Kasichayanula S, Liu X, Lacreta F. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter type 2. Clin Pharmacokinet 2014;53(1):17-27
32. EMDAC Background Document, Dapagliflozin, BMS-512148 NDA 202293. 2013. Available from: www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/endocrinologicandmetabolicdrugs advisorycommittee/ucm378079.pdf [Last accessed 6 September 2014].
33. Van der Walt J-S, Hong Y, Zhang L, et al. A nonlinear mixed effects pharmacokinetic model for dapagliflozin and dapagliflozin 3-O-glucuronide in renal or hepatic impairment. CPT Pharmacometrics Syst Pharmacol 2013;2(5):e42
34. Scheen AJ. Drug-drug interactions with sodium-glucose cotransporters type 2 (SGLT2) inhibitors, new oral glucoselowering agents for the management of type 2 diabetes mellitus. Clin Pharmacokinet 2014;53(4):295-304
35. Kasichayanula S, Chang M, Liu X, et al. Lack of pharmacokinetic interactions between dapagliflozin and simvastatin, valsartan, warfarin, or digoxin. Adv Ther 2012;29(2):163-77.
36. 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(10):928-38
37. Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults. Diabetes Care 2012;35:2650-64
38. Kasichayanula S, Liu X, Pe Benito M, et al. The influence of kidney function on dapagliflozin exposure, metabolism and pharmacodynamics in healthy subjects and in patients with type 2 diabetes mellitus. Br J Clin Pharmacol 2013;76(3):432-44
39. US Full Prescribing Information and Medication Guide for Farxiga-(dapagliflozin) tablets. Available from: http://packageinserts.bms.com/pi/pi-farxiga.pdf [Last accessed 6 September 2014]
40. Kasichayanula S, Liu X, Zhang W, et al. Influence of hepatic impairment on the pharmacokinetics and safety profile of dapagliflozin: an open-label, parallelgroup, single-dose study. Clin Ther 2011;33(11):1798-808
41. Komoroski B, Vachharajani N, Boulton D, et al. Dapagliflozin, a novel SGLT2 inhibitor, induces dosedependent glucosuria in healthy subjects. Clin Pharmacol Ther 2009;85(5):520-6
42. Rosenwasser RF, Sultan S, Sutton D, et al. SGLT-2 inhibitors and their potential in the treatment of diabetes. Diabetes Metab Syndr Obes 2013;6:453-67
43. Bailey CJ, Iqbal N, T'joen C, List JF. Dapagliflozin monotherapy in drug-näve patients with diabetes: a randomizedcontrolled trial of low-dose range. Diabetes Obes Metab 2012;14(10):951-9
44. 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, placebocontrolled, phase 3 trial. Diabetes Care 2010;33(10):2217-24.
45. 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;66(5):446-56.
46. List JF, Woo V, Morales E, et al. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 2009;32(4):650-7.
47. 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, double-blind, placebocontrolled trial. Lancet 2010;375(9733):2223-33.
48. Bailey CJ, Gross JL, Hennicken D, et al. Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, doubleblind, placebo-controlled 102-week trial. BMC Med 2013;11:43.
49. 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;97(3):1020-31.
50. Bolinder J, Ljunggren O, Johansson L, et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab 2014;16:159-69.
51. Jabbour SA, Hardy E, Sugg J, Parikh S. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebocontrolled study. Diabetes Care 2014;37(3):740-50.
52. 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(10):928-38
53. 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(7):1473-8.
54. 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 insulinindependent treatment. Diabetes Care 2009;32(9):1656-62.
55. 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(6):405-15.
56. 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 non inferiority trial. Diabetes Care 2011;34(9):2015-22.
57. Nauck MA, Del Prato S, Durán-Garcá S, et al. Durability of glycaemic efficacy over 2-years with dapagliflozin versus glipizide as add-on therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin. Diabetes Obes Metab 2014;16(11):1111-20.
58. 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;12(6):510-16.
59. Leiter LA, Cefalu WT, de Bruin TW, et al. Dapagliflozin added to usual care in individuals with type 2 diabetes mellitus with preexisting cardiovascular disease: a 24-week, multicenter, randomized, double-blind, placebocontrolled study with a 28-week extension. J Am Geriatr Soc 2014;62:1252-62.
60. 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(4):962-71.
61. FDA Briefing Document, NDA 202293. 2011. Available from: http://www.fda. gov/downloads/AdvisoryCommittee/UCM262994.pdf [Last accessed 6 September 2014]
62. Johnsson KM, Ptaszynska A, Schmitz B, et al. Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin. J Diabetes Complications 2013;27(5):479-84.
63. Johnsson KM, Ptaszynska A, Schmitz B, et al. Urinary tract infections in patients with diabetes treated with dapagliflozin. J Diabetes Complications 2013;27(5):473-8.
64. Grandy S, Langkilde AM, Sugg JE, et al. Health-related quality of life (EQ-5D) among type 2 diabetes mellitus patients treated with dapagliflozin over 2 years. Int J Clin Pract 2014;68(4):486-94
65. Grandy S, Hashemi M, Langkilde AM, et al. Changes in weight loss-related quality of life among type 2 diabetes mellitus patients treated with dapagliflozin. Diabetes Obes Metab 2014;16:645-50
66. Kim Y, Babu AR. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes. Diabetes Metab Syndr Obes 2012;5:313-27
67. Multicenter trial to evaluate the effect of dapagliflozin on the incidence of cardiovascular events (DECLARETIMI58), study design. Available from: http://clinicaltrials.gov/show/NCT01730534 [Last accessed 5 September 2014]
68. Salvo MC, Brooks AD, Thacker SM. Patient considerations in the management of type 2 diabetes-critical appraisal of dapagliflozin. Patient Prefer Adherence 2014;8:493-502