Twice-daily dapagliflozin co-administered with metformin in type 2 diabetes: A 16-week randomized, placebo-controlled clinical trial

Diabetes, Obesity and Metabolism

Volumn 17, Issue 1, 2015, Pages 42-51

  Schumm Draeger, P M ^a   Burgess, L ^b   Koranyi L ^c   Hruba, V ^d   Hamer Maansson, J E ^d   de Bruin, T W A ^d  

^a Teaching Hospital   (Germany)

^b STELLENBOSCH UNIVERSITY   (South Africa)

^c Drug Research Center Gyógyszervizsgáló Központ   (Hungary)

^d ASTRAZENECA   (United Kingdom)

Author keywords

Metformin; Phase III study; SGLT2 inhibitor; Type 2 diabetes

Indexed keywords

DAPAGLIFLOZIN; GLUCOSE; HEMOGLOBIN A1C; METFORMIN; 2-(3-(4-ETHOXYBENZYL)-4-CHLOROPHENYL)-6-HYDROXYMETHYLTETRAHYDRO-2H-PYRAN-3,4,5-TRIOL; AGENTS AFFECTING WATER, MOLECULE OR ION TRANSPORT; ANTIDIABETIC AGENT; BENZHYDRYL DERIVATIVE; GLUCOSIDE; GLYCOSYLATED HEMOGLOBIN; HEMOGLOBIN A1C PROTEIN, HUMAN; SODIUM GLUCOSE COTRANSPORTER 2;

ADULT; AGED; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; DEHYDRATION; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; FRACTURE; GASTROINTESTINAL DISEASE; GENITAL TRACT INFECTION; GLUCOSE BLOOD LEVEL; HUMAN; HYPOGLYCEMIA; HYPOTENSION; HYPOVOLEMIA; KIDNEY FAILURE; KIDNEY INFECTION; MAJOR CLINICAL STUDY; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; PHASE 3 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; TREATMENT OUTCOME; URINARY TRACT INFECTION; ADVERSE EFFECTS; ANTAGONISTS AND INHIBITORS; BLOOD; CLINICAL TRIAL; DIABETES MELLITUS, TYPE 2; DOSE RESPONSE; DRUG ADMINISTRATION; DRUG COMBINATION; DRUG EFFECTS; DRUG RESISTANCE; EUROPE; FEASIBILITY STUDY; HYPERGLYCEMIA; MIDDLE AGED; MULTICENTER STUDY; SOUTH AFRICA;

AGED; BENZHYDRYL COMPOUNDS; BODY WEIGHT; DIABETES MELLITUS, TYPE 2; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; DRUG RESISTANCE; DRUG THERAPY, COMBINATION; EUROPE; FEASIBILITY STUDIES; FEMALE; GLUCOSIDES; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPERGLYCEMIA; HYPOGLYCEMIC AGENTS; MALE; MEMBRANE TRANSPORT MODULATORS; METFORMIN; MIDDLE AGED; SODIUM-GLUCOSE TRANSPORTER 2; SOUTH AFRICA;

EID: 84919487701     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12387     Document Type: Article

References (32)

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; 35: 1364-1379.
2. American Diabetes Association. Standards of medical care in diabetes - 2013. Diabetes Care 2013; 36(Suppl. 1): S11-S66.
3. Turner R, Cull C, Holman R. United Kingdom Prospective Diabetes Study 17: a 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus. Ann Intern Med 1996; 124: 136-145.
4. 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; 321: 405-412.
5. 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.
6. 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: 446-456.
7. Nauck MA, Del PS, 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.
8. 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.
9. Komoroski B, Vachharajani N, Feng Y, Li L, Kornhauser D, Pfister M. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin Pharmacol Ther 2009; 85: 513-519.
10. 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: 2217-2224.
11. List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 2009; 32: 650-657.
12. 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: 1473-1478.
13. Strojek K, Yoon K, Hruba V, Elze M, Langkilde A, Parikh S. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomised, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab 2011; 13: 928-938.
14. 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.
15. Bailey CJ, Gross JL, Hennicken D, Iqbal N, Mansfield TA, List JF. Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial. BMC Med 2013; 11: 43.
16. 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: 1020-1031.
17. Garber AJ, Duncan TG, Goodman AM, Mills DJ, Rohlf JL. Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose-response trial. Am J Med 1997; 103: 491-497.
18. Dickson M, Plauschinat CA. Compliance with antihypertensive therapy in the elderly: a comparison of fixed-dose combination amlodipine/benazepril versus component-based free-combination therapy. Am J Cardiovasc Drugs 2008; 8: 45-50.
19. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001; 23: 1296-1310.
20. Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med 2007; 120: 713-719.
21. Melikian C, White TJ, Vanderplas A, Dezii CM, Chang E. Adherence to oral antidiabetic therapy in a managed care organization: a comparison of monotherapy, combination therapy, and fixed-dose combination therapy. Clin Ther 2002; 24: 460-467.
22. Ho PM, Rumsfeld JS, Masoudi FA et al. Effect of medication nonadherence on hospitalization and mortality among patients with diabetes mellitus. Arch Intern Med 2006; 166: 1836-1841.
23. Glucophage [prescribing information]. Geneva, Switzerland: Merck Serono. Available from URL: http://www.medicines.org.uk/emc/medicine/1043/SPC/Glucophage+500+mg+and+850+mg+film+coated+tablets/, 2010. Accessed 18 August 2014.
24. Nathan DM, Buse JB, Davidson MB et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009; 32: 193-203.
25. Hochberg Y. A Sharper Bonferroni procedure for multiple tests of significance. Biometrika 1988; 75: 800-802.
26. Zhang M, Tsiatis AA, Davidian M. Improving efficiency of inferences in randomized clinical trials using auxiliary covariates. Biometrics 2008; 64: 707-715.
27. Tsiatis AA, Davidian M, Zhang M, Lu X. Covariate adjustment for two-sample treatment comparisons in randomized clinical trials: a principled yet flexible approach. Stat Med 2008; 27: 4658-4677.
28. Esposito K, Chiodini P, Capuano A, Maiorino MI, Bellastella G, Giugliano D. Baseline glycemic parameters predict the hemoglobin A response to DPP-4 inhibitors: meta-regression analysis of 78 randomized controlled trials with 20, 053 patients. Endocrine 2014; 46: 43-51.
29. Hardy E, Salsali A, Hruba V et al. Efficacy increases with increasing baseline HbA1c category with dapagliflozin therapy. Diabetes 2012; 61(Suppl. 1): A23 Abstract 82-OR.
30. Bloomgarden ZT, Dodis R, Viscoli CM, Holmboe ES, Inzucchi SE. Lower baseline glycemia reduces apparent oral agent glucose-lowering efficacy: a meta-regression analysis. Diabetes Care 2006; 29: 2137-2139.
31. Defronzo RA, Stonehouse AH, Han J, Wintle ME. Relationship of baseline HbA1c and efficacy of current glucose-lowering therapies: a meta-analysis of randomized clinical trials. Diabet Med 2010; 27: 309-317.
32. Ptaszynska A, Johnsson K, Apanovitch AM, Sugg J, Parikh SJ, List JF. Effect of dapagliflozin on renal function. Diabetes 2012; 61(Suppl. 1): A283 Abstract 1098-P.