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

Abstract

Diabet. Med. 27, 1024–1032 (2010) 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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Cited by papers we hold 3

• Targeting GLP-1 receptor trafficking to improve agonist efficacy · 2018
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• Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin · 2013
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• Randomized, double‐blind, placebo‐controlled trial of the once‐daily GLP ‐1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea ( GetGoal ‐L‐Asia) · 2012
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