Liraglutide Improves Glucose Control And Increases Weight Loss In Type 2 Diabetes Patients (LEAD-3 Mono Study)

Main Category: Diabetes
Article Date: 25 Sep 2008 - 3:00 PDT

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Liraglutide, a new treatment for type 2 diabetes, improves blood glucose control compared with a conventional oral treatment glimepiride. Patients given liraglutide injections also recorded increases in weight loss and decreases in blood pressure. These are the conclusions of an Article published early Online and in an upcoming edition of The Lancet, written by Dr Alan Garber, Baylor College of Medicine, Houston, TX, USA, and colleagues.

In this randomised-controlled phase III trial, 746 patients with early type 2 diabetes were assigned to once daily liraglutide 1•2 mg, (251 patients) or 1•8 mg (247 patients) or glimepiride 8 mg (248 patients) for one year. The primary outcome was the change in proportion of glycosylated haemoglobin* (HbA1c). Patients in the three groups had a mean HbA1c of 8•3-8•4% at baseline. The researchers found that HbA1c decreased by 0•51% in the glimepiride group, while in the liraglutide 1•2 mg group the reduction was 0•84% and in the liraglutide 1•8 mg group it was 1•14%. Proportions of patients achieving HbA1c of both less than 7•0% and less than 6•5% (two internationally accepted targets) were higher for both liraglutide group patients than for glimepiride patients, in both patients who had been receiving treatment before and those who were treatment naive. Five patients in the liraglutide 1•2 mg, one in the 1•8 mg group and none in the glimepiride group discontinued treatment because of vomiting.

Further, the researchers found that participants in the liraglutide groups lost weight (around 2 kg) while those in the glimepiride group gained weight (1 kg), when adjusted for the effects of nausea. Systolic blood pressure fell by 0•7 mm Hg in the glimepiride group, compared with 2•1 mg Hg in the liraglutide 1•2 mg group and 3•6 mm Hg in the liraglutide 1•8 mg group. These blood pressure results were only statistically significant for the liraglutide 1•8 mg group versus glimepiride. The authors conclude: "Treatment with liraglutide as monotherapy provided better glycaemic control for 52-weeks than did glimepiride, a traditional first-line therapy for type 2 diabetes mellitus, in participants previously treated with either diet and exercise or oral antidiabetic monotherapy. Liraglutide improved glycaemic control with a low rate of hypoglycaemia...On the basis of these results, we conclude that liraglutide is safe and effective as initial pharmacological therapy for type 2 diabetes mellitus and has advantages over other drugs used in monotherapy, such as greater reductions in weight, the number of hypoglycaemic events, and systolic blood pressure."

In an accompanying Comment, Dr Sten Madsbad, Hvidovre Hosptial and University of Copenhagen, Denmark, says that treatments such as liraglutide offer new options in the treatment of type 2 diabetes, but adds that their final role "remains to be clarified, after carefully conducted long-term trials with cardiovascular endpoints and safety data."

Glycosylated haemoglobin (HbA1c) is a form of haemoglobin used primarily to identify the average plasma glucose concentration over prolonged periods of time. The HbA1c level is proportional to average blood glucose concentration over the previous four weeks to three months. Depending on which international standard is used, the target for type 2 diabetes patients is to reduce their proportion of HbA1c to 7•0% or 6•5%.

"Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial."
Dr Alan Garber PhD, Robert Henry MD, Robert Ratner MD, Pedro A Garcia-Hernandez MD, Hiromi Rodriguez-Pattzi MD, Israel Olvera-Alvarez MD, Paula M Hale PhD, Milan Zdravkovic Milan Zdravkovic MD
The Lancet DOI:10.1016/S0140-6736(08)61246-5
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The Lancet