Document Detail


Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial.
MedLine Citation:
PMID:  20609969     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Diabetes treatments are needed that are convenient, provide effective glycaemic control, and do not cause weight gain. We aimed to test the hypothesis that improvement in haemoglobin A(1c) (HbA(1c)) achieved with once weekly exenatide was superior to that achieved with insulin glargine titrated to glucose targets. METHODS: In this 26-week, open-label, randomised, parallel study, we compared exenatide with insulin glargine in adults with type 2 diabetes who had suboptimum glycaemic control despite use of maximum tolerated doses of blood-glucose-lowering drugs for 3 months or longer. Patients were randomly assigned to add exenatide (2 mg, once-a-week injection) or insulin glargine (once-daily injection, starting dose 10 IU, target glucose range 4.0-5.5 mmol/L) to their blood-glucose-lowering regimens. Randomisation was with a one-to-one allocation and block size four, stratified according to country and concomitant treatment (70% metformin only; 30% metformin plus sulphonylurea). Participants and clinical investigators were not masked to assignment, but investigators analysing data were. The primary endpoint was change in HbA(1c) from baseline, and analysis of this outcome was by modified intention to treat for all patients who received at least one dose of study drug. This trial is registered at ClinicalTrials.gov, number NCT00641056. FINDINGS: 456 patients were randomly allocated to treatment and were included in the modified intention-to-treat analysis (233 exenatide, 223 insulin glargine). Participants who received at least one dose of study drug and for whom baseline and at least one postbaseline measurement of HbA(1c) were available were included in the primary efficacy analysis. Change in HbA(1c) at 26 weeks was greater in patients taking exenatide (n=228; -1.5%, SE 0.05) than in those taking insulin glargine (n=220; -1.3%, 0.06; treatment difference -0.16%, 0.07, 95% CI -0.29 to -0.03). 12 (5%) of 233 patients allocated to exenatide and two (1%) of 223 taking insulin glargine discontinued participation because of adverse events (p=0.012). A planned extension period (up to 2.5 years' duration) is in progress. INTERPRETATION: Once weekly exenatide is an important therapeutic option for patients for whom risk of hypoglycaemia, weight loss, and convenience are particular concerns. FUNDING: Amylin Pharmaceuticals; Eli Lilly and Company.
Authors:
Michaela Diamant; Luc Van Gaal; Stephen Stranks; Justin Northrup; Dachuang Cao; Kristin Taylor; Michael Trautmann
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Publication Detail:
Type:  Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Lancet     Volume:  375     ISSN:  1474-547X     ISO Abbreviation:  Lancet     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-07-08     Completed Date:  2010-07-20     Revised Date:  2010-10-14    
Medline Journal Info:
Nlm Unique ID:  2985213R     Medline TA:  Lancet     Country:  England    
Other Details:
Languages:  eng     Pagination:  2234-43     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Diabetes Centre, VU University Medical Centre, Amsterdam, Netherlands. m.diamant@vumc.nl
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00641056
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MeSH Terms
Descriptor/Qualifier:
Blood Glucose / analysis
Diabetes Mellitus, Type 2 / blood,  drug therapy*
Drug Administration Schedule
Female
Glucagon-Like Peptide 1 / agonists
Hemoglobin A, Glycosylated / analysis
Humans
Hypoglycemic Agents / administration & dosage*
Injections, Subcutaneous
Insulin / analogs & derivatives*,  therapeutic use
Male
Middle Aged
Peptides / administration & dosage*
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Hemoglobin A, Glycosylated; 0/Hypoglycemic Agents; 0/Peptides; 0/glargine; 11061-68-0/Insulin; 141732-76-5/exenatide; 89750-14-1/Glucagon-Like Peptide 1
Comments/Corrections
Comment In:
Lancet. 2010 Sep 25;376(9746):1052-3; author reply 1053   [PMID:  20870094 ]
Lancet. 2010 Jun 26;375(9733):2198-9   [PMID:  20609957 ]
Lancet. 2010 Aug 7;376(9739):393-4   [PMID:  20580425 ]

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