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)

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 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 vs exenatide −2·87 kg). Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0·448, p 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.