Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial

Clifford J. Bailey, Jorge L. Gross, Delphine Hennicken, Nayyar Iqbal, Traci A. Mansfield, James F. List

Research output: Contribution to journalArticle

Abstract

Background: Management of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population.Methods: This was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5 to 5, or 10 mg) plus open-label metformin (=1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight.Results: A total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P
Original languageEnglish
Number of pages10
JournalBMC Medicine
Volume11
Issue number1
DOIs
Publication statusPublished - 20 Feb 2013

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Metformin
Type 2 Diabetes Mellitus
Placebos
Sodium-Glucose Transport Proteins
Glycosylated Hemoglobin A
Therapeutics
Fasting
Observation
Clinical Trials
Weights and Measures
Glucose
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Population

Bibliographical note

© 2013 Bailey et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords

  • dapagliflozin
  • metformin
  • SGLT2
  • sodium-glucose cotransporter 2
  • glycemic control
  • type 2 diabetes

Cite this

Bailey, Clifford J. ; Gross, Jorge L. ; Hennicken, Delphine ; Iqbal, Nayyar ; Mansfield, Traci A. ; List, James F. / Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin : a randomized, double-blind, placebo-controlled 102-week trial. In: BMC Medicine. 2013 ; Vol. 11, No. 1.
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Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin : a randomized, double-blind, placebo-controlled 102-week trial. / Bailey, Clifford J.; Gross, Jorge L.; Hennicken, Delphine; Iqbal, Nayyar; Mansfield, Traci A.; List, James F.

In: BMC Medicine, Vol. 11, No. 1, 20.02.2013.

Research output: Contribution to journalArticle

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T1 - Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin

T2 - a randomized, double-blind, placebo-controlled 102-week trial

AU - Bailey, Clifford J.

AU - Gross, Jorge L.

AU - Hennicken, Delphine

AU - Iqbal, Nayyar

AU - Mansfield, Traci A.

AU - List, James F.

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N2 - Background: Management of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population.Methods: This was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5 to 5, or 10 mg) plus open-label metformin (=1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight.Results: A total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P

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