Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)

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• 作者：John B Buse ; Julio Rosenstock ; Giorgio Sesti ; Wolfgang E Schmidt ; Eduard Montanya ; Jason H Brett ; Marcin Zychma ; Lawrence Blonde ; for the LEAD-6 Study Group
• 刊名：The Lancet
• 出版年：2009
• 出版时间：4 July 2009-10 July 2009
• 年：2009
• 卷：374
• 期：9683
• 页码：39-47
• 全文大小：243 K

文摘

Summary

Background

Unlike most antihyperglycaemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists have a glucose-dependent action and promote weight loss. We compared the efficacy and safety of liraglutide, a human GLP-1 analogue, with exenatide, an exendin-based GLP-1 receptor agonist.

Methods

Adults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin, sulphonylurea, or both, were stratified by previous oral antidiabetic therapy and randomly assigned to receive additional liraglutide 1·8 mg once a day (n=233) or exenatide 10 μg twice a day (n=231) in a 26-week open-label, parallel-group, multinational (15 countries) study. The primary outcome was change in glycosylated haemoglobin (HbA_1c). Efficacy analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00518882.

Findings

Mean baseline HbA_1c for the study population was 8·2 % . Liraglutide reduced mean HbA_1c significantly more than did exenatide (−1·12 % [SE 0·08] vs −0·79 % [0·08]; estimated treatment difference −0·33; 95 % CI −0·47 to −0·18; p<0·0001) and more patients achieved a HbA_1c value of less than 7 % (54 % vs 43 % , respectively; odds ratio 2·02; 95 % CI 1·31 to 3·11; p=0·0015). Liraglutide reduced mean fasting plasma glucose more than did exenatide (−1·61 mmol/L [SE 0·20] vs −0·60 mmol/L [0·20]; estimated treatment difference −1·01 mmol/L; 95 % CI −1·37 to −0·65; p<0·0001) but postprandial glucose control was less effective after breakfast and dinner. Both drugs promoted similar weight losses (liraglutide −3·24 kg vs exenatide −2·87 kg). Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0·448, p<0·0001) and minor hypoglycaemia less frequent with liraglutide than with exenatide (1·93 vs 2·60 events per patient per year; rate ratio 0·55; 95 % CI 0·34 to 0·88; p=0·0131; 25·5 % vs 33·6 % had minor hypoglycaemia). Two patients taking both exenatide and a sulphonylurea had a major hypoglycaemic episode.

Interpretation

Liraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated. The results suggest that liraglutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations.

Funding

Novo Nordisk A/S.