An article published Online First and in a future edition of The Lancet reports that liraglutide reduces weight and the prevalence of risk factors in obese people without diabetes. In addition, high doses of liraglutide cause greater weight loss than orlistat. The article is the work of Professor Arne Astrup, Department of Human Nutrition, University of Copenhagen, Denmark, and colleagues.
In the last two decades, the rate of obesity has risen three-fold. It is more than 30 percent in some European countries. In Europe, about 50 percent of all adults are categorized as overweight. Obesity increases the risk of hypertension, diabetes, and atherosclerosis. These are all risk factors for the leading cause of death worldwide which is cardiovascular disease. Additionally, obesity is linked with a reduced quality of life. There are very few safe and effective drugs presently available for the treatment of obesity. As a result, there is a need for alternative approaches to weight loss that are safe and easily tolerated and that can also lower the risks associated with obesity. The researchers of this randomised controlled trial studied the effect of liraglutide on bodyweight and tolerability in obese individuals without type 2 diabetes.
The study involved 564 people and took place in 19 sites in Europe. The participants were aged between 18 and 65 years with a body-mass index of 30 to 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 to 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 containing approximately 500 calories less than what they needed each day. In addition, participants augmented their physical activity throughout the trial.
Findings indicated that participants on liraglutide lost considerably more weight than did those on placebo and orlistat. Average 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 percentage of individuals (76 percent) lost more than 5 percent weight with liraglutide 3•0 mg than with placebo (30 percent) or orlistat (44 percent). At all doses, liraglutide reduced blood pressure. At the start of the study, approximately a third of patients in each group had prediabetes. This is defined as poor blood glucose control which still does not qualify as diabetes. Liraglutide reduced the prevalence of prediabetes (84 to 96 percent 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 temporary and rarely led to discontinuation of treatment.
The authors remark: “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 write in conclusion: “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 continue by recommending further studies, with longer follow-up than twenty weeks. This is now necessary to determine the long-term risk-benefit profile for liraglutide.
In an associated note, Dr George A Bray from the Division of Clinical Obesity and Metabolism, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA, remarks: “Today’s important report shows a dose-related reduction of food intake and bodyweight in overweight and obese individuals treated with liraglutide.”
Dr Bray comments that one limitation to the use of drugs such as liraglutide is that they require an injection. He remarks: “Whether long-term use of an injectable drug is palatable as a treatment for obesity is yet to be established.”
“Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study”
Arne Astrup, Stephan Rössner, Luc Van Gaal, Aila Rissanen, Leo Niskanen, Mazin Al Hakim, Jesper Madsen, Mads F Rasmussen, Michael E J Lean, on behalf of the NN8022-1807 Study Group
Written by Stephanie Brunner (B.A.)