@article{00ba3dabdfe14e80862412991f1e6550,
title = "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)",
abstract = "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 microg 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.",
keywords = "Analysis of Variance, Blood Glucose, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Glucagon-Like Peptide 1, Hemoglobin A, Glycosylated, Humans, Hypoglycemia, Hypoglycemic Agents, Injections, Subcutaneous, Linear Models, Logistic Models, Male, Middle Aged, Nausea, Peptides, Treatment Outcome, Venoms, Weight Loss",
author = "Buse, {John B} and Julio Rosenstock and Giorgio Sesti and Schmidt, {Wolfgang E} and Eduard Montanya and Brett, {Jason H} and Marcin Zychma and Lawrence Blonde and NN NN",
note = "Endokrinologisk afdeling har deltaget i studiegruppen",
year = "2009",
doi = "10.1016/S0140-6736(09)60659-0",
language = "English",
volume = "374",
pages = "39--47",
journal = "Lancet",
issn = "1474-547X",
publisher = "Elsevier BV",
number = "9683",
}