Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study.
BACKGROUND
The frequency of obesity has risen dramatically in recent years but only few safe and effective drugs are currently available. We assessed the effect of liraglutide on bodyweight and tolerability in obese individuals without type 2 diabetes.


METHODS
We did a double-blind, placebo-controlled 20-week trial, with open-label orlistat comparator in 19 sites in Europe. 564 individuals (18-65 years of age, body-mass index 30-40 kg/m2) were randomly assigned, with a telephone or web-based system, 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 individuals had a 500 kcal per day energy-deficit diet and increased their physical activity throughout the trial, including the 2-week run-in. Weight change analysed by intention to treat was the primary endpoint. An 84-week open-label extension followed. This study is registered with ClinicalTrials.gov, number NCT00422058.


RESULTS
Participants on liraglutide lost significantly more weight than did those on placebo (p=0.003 for liraglutide 1.2 mg and p<0.0001 for liraglutide 1.8-3.0 mg) and orlistat (p=0.003 for liraglutide 2.4 mg and p<0.0001 for liraglutide 3.0 mg). Mean weight loss with liraglutide 1.2-3.0 mg was 4.8 kg, 5.5 kg, 6.3 kg, and 7.2 kg compared with 2.8 kg with placebo and 4.1 kg with orlistat, and was 2.1 kg (95% CI 0.6-3.6) to 4.4 kg (2.9-6.0) greater than that with placebo. More individuals (76%, n=70) lost more than 5% weight with liraglutide 3.0 mg that with placebo (30%, n=29) or orlistat (44%, n=42). Liraglutide reduced blood pressure at all doses, and 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.


CONCLUSIONS
Liraglutide treatment over 20 weeks is well tolerated, induces weight loss, improves certain obesity-related risk factors, and reduces prediabetes.


BACKGROUND
Novo Nordisk A/S, Bagsvaerd, Denmark.
Astrup
Arne
A
Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark. ast@life.ku.dk
Rössner
Stephan
S
Van Gaal
Luc
L
Rissanen
Aila
A
Niskanen
Leo
L
Al Hakim
Mazin
M
Madsen
Jesper
J
Rasmussen
Mads F
MF
Lean
Michael E J
ME
D000704:Analysis of Variance; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007279:Injections, Subcutaneous; D007783:Lactones / Q000627:therapeutic use; D000069450:Liraglutide; D016015:Logistic Models; D008297:Male; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D000077403:Orlistat; D011236:Prediabetic State / Q000150:complications / Q000517:prevention & control; D012449:Safety; D016896:Treatment Outcome; D055105:Waist Circumference / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
D019440:Anti-Obesity Agents; D007783:Lactones; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077403:Orlistat