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

Lean, M. , Carraro, R., Finer, N., Hartvig, H., Lindegaard, M., Rössner, S., Van Gaal, L. and Astrup, A. (2014) Tolerability of nausea and vomiting and associations with weight loss in a randomized trial of liraglutide in obese, non-diabetic adults. International Journal of Obesity, 38(5), pp. 689-697. (doi: 10.1038/ijo.2013.149) (PMID:23942319) (PMCID:PMC4010971)

Abstract

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 among individuals on liraglutide and their influence on tolerability and body weight.<p></p> Design: A randomized, placebo-controlled, double-blind 20-week study with an 84-week extension (sponsor unblinded at 20 weeks, open-label after 1 year) in eight European countries (Clinicaltrials.gov: NCT00422058). Subjects: After commencing a 500-kcal/day deficit diet plus exercise, 564 participants (18–65 years, body mass index (BMI) 30–40 kg m−2) were randomly assigned (after a 2-week run-in period) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg), placebo or open-label orlistat (120 mg × 3 per day). After 1 year, participants on liraglutide/placebo switched to liraglutide 2.4 mg, and subsequently, to liraglutide 3.0 mg (based on 20-week and 1-year results, respectively).<p></p> Results: The intention-to-treat population comprised 561 participants (n=90–98 per arm, age 45.9±10.3 years, BMI 34.8±2.7 kg m−2 (mean±s.d.)). In year 1, more participants reported greater than or equal to1 episode of nausea/vomiting on treatment with liraglutide 1.2–3.0 mg (17–38%) than with placebo or orlistat (both 4%, Pless than or equal to0.001). 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 out of 93 (4%) reported withdrawals. The mean 1-year weight loss on treatment 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 (a treatment difference of 2.9 kg (95% confidence interval 0.5–5.3); P=0.02). Both weight losses were significantly greater than the respective weight losses for participants on placebo (P<0.001) or orlistat (P<0.05). Quality-of-life scores at 20 weeks improved similarly with or without nausea/vomiting on treatment with liraglutide 3.0 mg.<p></p> Conclusion: Transient nausea and vomiting on treatment with liraglutide 3.0 mg was associated with greater weight loss, although symptoms appeared tolerable and did not attenuate quality-of-life improvements. Improved data collection methods on nausea are warranted.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lean, Professor Michael
• Authors: Lean, M., Carraro, R., Finer, N., Hartvig, H., Lindegaard, M., Rössner, S., Van Gaal, L., and Astrup, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: International Journal of Obesity
• Publisher: Nature Publishing Group
• ISSN: 0307-0565
• ISSN (Online): 1476-5497
• Copyright Holders: Copyright © 2014 Macmillan Publishers Limited
• First Published: First published in International Journal of Obesity 38(5):689-397
• Publisher Policy: Reproduced under a Creative Commons License