Journal Article

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)

Brett, Jason H, Rosenstock, Julio, Zychma, Marcin, Blonde, Lawrence, Montanya, Eduard, Sesti, Giorgio, Buse, John B, Schmidt, Wolfgang E

2009

Overview

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. 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. 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. 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. Novo Nordisk A/S.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Analysis of Variance / Apoptosis / Biological and medical sciences / Blood Glucose - drug effects / Blood Glucose - metabolism / Clinical medicine / Clinical trials / Diabetes / Diabetes Mellitus, Type 2 - drug therapy / Diabetes Mellitus, Type 2 - metabolism / Diabetes. Impaired glucose tolerance / Dose-Response Relationship, Drug / Drug Administration Schedule / Drug therapy / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Female / General aspects / Glucagon-Like Peptide 1 - adverse effects / Glucagon-Like Peptide 1 - agonists / Glucagon-Like Peptide 1 - analogs & derivatives / Glucagon-Like Peptide 1 - chemistry / Glucagon-Like Peptide 1 - therapeutic use / Glycated Hemoglobin A - drug effects / Glycated Hemoglobin A - metabolism / Humans / Hypoglycemia - chemically induced / Hypoglycemic Agents - adverse effects / Hypoglycemic Agents - chemistry / Hypoglycemic Agents - therapeutic use / Injections, Subcutaneous / Internal Medicine / Linear Models / Liraglutide / Logistic Models / Male / Medical sciences / Middle Aged / Molecular structure / Nausea - chemically induced / Peptides - adverse effects / Peptides - chemistry / Peptides - therapeutic use / Pharmaceuticals / Treatment Outcome / Venoms - adverse effects / Venoms - chemistry / Venoms - therapeutic use / Weight Loss - drug effects