Liraglutide Reduces Weight And Risk Factors In Obese People Without Diabetes (Online First)

Main Category: Obesity / Weight Loss / Fitness
Article Date: 25 Oct 2009 - 0:00 PDT

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Liraglutide reduces weight and the prevalence of risk factors in obese people without diabetes. Furthermore, high doses of liraglutide cause greater weight loss than orlistat. These are the conclusions of an Article published Online First (http://www.thelancet.com) and in an upcoming edition of The Lancet, written by Professor Arne Astrup*, Department of Human Nutrition, University of Copenhagen, Denmark, and colleagues.

Over the past 20 years, the rate of obesity has risen three-fold and is more than 30% in some European countries. Around 50% of all adults in Europe are classified as overweight. Obesity increases the risk of hypertension, diabetes, and atherosclerosis, all risk factors for the leading cause of death worldwide-cardiovascular disease. Moreover, obesity is associated with a reduced quality of life. Few safe and effective drugs are currently available for the treatment of obesity. Therefore, alternative approaches to weight loss that are safe and well tolerated and that can lower the risks associated with obesity are needed. In this randomised controlled trial, the authors studied the effect of liraglutide on bodyweight and tolerability in obese individuals without type 2 diabetes.

The study took place in 19 sites in Europe, and analysed 564 people (18-65 years of age, body-mass index 30-40 kg/m²). Each was assigned to one of four liraglutide doses (1•2 mg, 1•8 mg, 2•4 mg, or 3•0 mg, n=90-95) or to placebo (n=98) administered once a day subcutaneously, or orlistat (120 mg, n=95) three times a day orally. All participants also followed a calorie-restricted diet, which contained approximately 500 calories less than they needed each day. Participants also increased their physical activity throughout the trial, including the 2-week run-in.

Participants on liraglutide lost significantly more weight than did those on placebo and orlistat. Mean weight loss with liraglutide doses 1•2, 1.8, 2.4 and 3•0 mg was 4•8 kg, 5•5 kg, 6•3 kg, and 7•2 kg respectively, compared with 2•8 kg with placebo and 4•1 kg with orlistat. A higher proportion of individuals (76%) lost more than 5% weight with liraglutide 3•0 mg than with placebo (30%) or orlistat (44%). Liraglutide reduced blood pressure at all doses. At the start of the study, around a third of patients in each group had prediabetes-that is, poor blood glucose control not yet bad enough to qualify as diabetes. Liraglutide reduced the prevalence of prediabetes (84-96% reduction) with 1•8-3•0 mg per day. Nausea and vomiting occurred more often in individuals on liraglutide than in those on placebo, but adverse events were mainly transient and rarely led to discontinuation of treatment.

The authors say: "Treatment with liraglutide, in addition to an energy-deficit diet and exercise programme, led to a sustained, clinically relevant, dose-dependent weight loss that was significantly greater than that with placebo (all doses) and orlistat (vs liraglutide 2•4 mg and 3•0 mg)."

They conclude: "The results of this study indicate the potential benefit of liraglutide, in conjunction with an energy-deficit diet, in the treatment of obesity and associated risk factors. Liraglutide offers a new mode of action for the treatment of obesity and improved efficacy compared with currently available therapies. Its effect on prediabetes suggests that it might be important for treating obese prediabetic individuals."

They add that further studies, with longer follow-up than 20 weeks, are now needed to establish the long-term risk-benefit profile for liraglutide.

In an accompanying Comment, Dr George A Bray. Division of Clinical Obesity and Metabolism, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA, says: "Today's important report shows a dose-related reduction of food intake and bodyweight in overweight and obese individuals treated with liraglutide."

Dr Bray adds that one limitation to the use of drugs such as liraglutide is that they require an injection. He says: "Whether long-term use of an injectable drug is palatable as a treatment for obesity is yet to be established."

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Source
The Lancet