Tolerability of nausea and vomiting and associations with weight loss in a randomized trial of liraglutide in obese, non-diabetic adults

Research output: Contribution to journalJournal articleResearchpeer-review

  • M E J Lean
  • R Carraro
  • N Finer
  • H Hartvig
  • M L Lindegaard
  • S Rössner
  • L Van Gaal
  • Arne Astrup
Background:Liraglutide 3.0 mg, with diet and exercise, produced substantial weight loss over 1 year that was sustained over 2 years in obese non-diabetic adults. Nausea was the most frequent side-effect.Objective:To evaluate routinely-collected data on nausea and vomiting with liraglutide, and their influence on tolerability and body weight.Design:A randomized, placebo-controlled, double-blind 20-week study with 84-week extension (sponsor unblinded at 20 weeks, open-label after 1 year) in 8 European countries ( NCT00422058).Subjects:After commencing a 500 kcal/day deficit diet plus exercise, 564 participants (18-65 years, BMI 30-40 kgm(-2)) were randomly assigned (after 2-week run-in) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4, or 3.0 mg), placebo, or open-label orlistat (120 mg × 3/day). After 1 year, participants on liraglutide/placebo switched to liraglutide 2.4 mg, and subsequently to 3.0 mg (based on 20-week and 1-year results, respectively).Results:The intention-to-treat population comprised 561 participants (n=90-98/arm, age 45.9±10.3 years, BMI 34.8±2.7 kgm(-2) [mean±s.d.]). In year 1, more participants reported 1 episode of nausea/vomiting with liraglutide 1.2-3.0 mg (17-38%) than with placebo or orlistat (both 4%, P0.001). Most episodes occurred during dose-escalation (weeks 1-6), with 'mild' or 'moderate' symptoms. Among participants on liraglutide 3.0 mg, 48% reported some nausea and 13% some vomiting, with considerable variation between countries, but only 4/93 (4%) withdrawals. Mean 1-year weight loss with liraglutide 3.0 mg from randomization was 9.2 kg for participants reporting nausea/vomiting episodes versus 6.3 kg for those with none (treatment-difference 2.9 kg [95% CI 0.5-5.3]; P=0.02). Both were significantly greater than placebo (P
Original languageEnglish
JournalInternational Journal of Obesity
Issue number5
Pages (from-to)689-697
Number of pages9
Publication statusPublished - 2014

ID: 50125890