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Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial

AIMS: To evaluate the dose–response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes. METHODS: Randomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabete...

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Detalles Bibliográficos
Autores principales: Ratner, R E, Rosenstock, J, Boka, G
Formato: Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068287/
https://www.ncbi.nlm.nih.gov/pubmed/20722676
http://dx.doi.org/10.1111/j.1464-5491.2010.03020.x
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author Ratner, R E
Rosenstock, J
Boka, G
author_facet Ratner, R E
Rosenstock, J
Boka, G
author_sort Ratner, R E
collection PubMed
description AIMS: To evaluate the dose–response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes. METHODS: Randomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabetes inadequately controlled [glycated haemoglobin (HbA(1c)) ≥ 7.0 and < 9.0% (≥ 53 and < 75 mmol/mol)] on metformin (≥ 1000 mg/day) treated with subcutaneous lixisenatide doses of 5, 10, 20 or 30 μg once daily or twice daily or placebo. The primary end-point was change in HbA(1c) from baseline to 13 weeks in the intent-to-treat population. RESULTS: Lixisenatide significantly improved mean HbA(1c) from a baseline of 7.55% (59.0 mmol/mol); respective mean reductions for 5, 10, 20 and 30 μg doses were 0.47, 0.50, 0.69 and 0.76% (5.1, 5.5, 7.5 and 8.3 mmol/mol), on once-daily and 0.65, 0.78, 0.75 and 0.87% (7.1, 8.5, 8.2 and 9.5 mmol/mol) on twice-daily administrations vs. 0.18% (2.0 mmol/mol) with placebo (all P< 0.01 vs. placebo). Target HbA(1c) < 7.0% (53 mmol/mol) at study end was achieved in 68% of patients receiving 20 and 30 μg once-daily lixisenatide vs. 32% receiving placebo (P< 0.0001). Dose-dependent improvements were observed for fasting, postprandial and average self-monitored seven-point blood glucose levels. Weight changes ranged from −2.0 to −3.9 kg with lixisenatide vs. −1.9 kg with placebo. The most frequent adverse event was mild-to-moderate nausea. CONCLUSIONS: Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose–response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 μg once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies.
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spelling pubmed-30682872011-04-02 Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial Ratner, R E Rosenstock, J Boka, G Diabet Med Original Articles AIMS: To evaluate the dose–response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes. METHODS: Randomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabetes inadequately controlled [glycated haemoglobin (HbA(1c)) ≥ 7.0 and < 9.0% (≥ 53 and < 75 mmol/mol)] on metformin (≥ 1000 mg/day) treated with subcutaneous lixisenatide doses of 5, 10, 20 or 30 μg once daily or twice daily or placebo. The primary end-point was change in HbA(1c) from baseline to 13 weeks in the intent-to-treat population. RESULTS: Lixisenatide significantly improved mean HbA(1c) from a baseline of 7.55% (59.0 mmol/mol); respective mean reductions for 5, 10, 20 and 30 μg doses were 0.47, 0.50, 0.69 and 0.76% (5.1, 5.5, 7.5 and 8.3 mmol/mol), on once-daily and 0.65, 0.78, 0.75 and 0.87% (7.1, 8.5, 8.2 and 9.5 mmol/mol) on twice-daily administrations vs. 0.18% (2.0 mmol/mol) with placebo (all P< 0.01 vs. placebo). Target HbA(1c) < 7.0% (53 mmol/mol) at study end was achieved in 68% of patients receiving 20 and 30 μg once-daily lixisenatide vs. 32% receiving placebo (P< 0.0001). Dose-dependent improvements were observed for fasting, postprandial and average self-monitored seven-point blood glucose levels. Weight changes ranged from −2.0 to −3.9 kg with lixisenatide vs. −1.9 kg with placebo. The most frequent adverse event was mild-to-moderate nausea. CONCLUSIONS: Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose–response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 μg once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies. Blackwell Publishing Ltd 2010-09 /pmc/articles/PMC3068287/ /pubmed/20722676 http://dx.doi.org/10.1111/j.1464-5491.2010.03020.x Text en Copyright © 2010 Diabetes UK http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Original Articles
Ratner, R E
Rosenstock, J
Boka, G
Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial
title Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial
title_full Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial
title_fullStr Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial
title_full_unstemmed Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial
title_short Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial
title_sort dose-dependent effects of the once-daily glp-1 receptor agonist lixisenatide in patients with type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068287/
https://www.ncbi.nlm.nih.gov/pubmed/20722676
http://dx.doi.org/10.1111/j.1464-5491.2010.03020.x
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