title: Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide.
abstract: OBJECTIVE
  Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers.
  
  
  METHODS
  A total of 564 adults (n=90-98 per group; body mass index 30-40 kg m(-2)) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n=90-95), placebo (n=98) or open-label orlistat (120 mg × 3, n=95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007-April 2009 and is registered with Clinicaltrials.gov, number NCT00480909.
  
  
  RESULTS
  From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7-8.0) more weight than those on placebo and 3.8 kg (1.6-6.0) more than those on orlistat (P0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n=184) lost 3.0 kg (1.3-4.7) more weight than those on orlistat (n=95; P<0.001). Completers on liraglutide 2.4/3.0 mg (n=92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids.
  
  
  CONCLUSIONS
  Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors.
authors.affiliation: Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Rolighedsvej 30, Frederiksberg C, Denmark. ast@life.ku.dk
authors.forename: A
authors.initials: A
authors.lastname: Astrup
authors.forename: R
authors.initials: R
authors.lastname: Carraro
authors.forename: N
authors.initials: N
authors.lastname: Finer
authors.forename: A
authors.initials: A
authors.lastname: Harper
authors.forename: M
authors.initials: M
authors.lastname: Kunesova
authors.forename: M E J
authors.initials: ME
authors.lastname: Lean
authors.forename: L
authors.initials: L
authors.lastname: Niskanen
authors.forename: M F
authors.initials: MF
authors.lastname: Rasmussen
authors.forename: A
authors.initials: A
authors.lastname: Rissanen
authors.forename: S
authors.initials: S
authors.lastname: Rössner
authors.forename: M J
authors.initials: MJ
authors.lastname: Savolainen
authors.forename: L
authors.initials: L
authors.lastname: Van Gaal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005060:Europe / Q000453:epidemiology; D005081:Exercise Therapy / Q000379:methods; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D011236:Prediabetic State / Q000178:diet therapy / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D040242:Risk Reduction Behavior; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects; D055815:Young Adult
chemical_list: D019440:Anti-Obesity Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1