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


METHODS
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).


METHODS
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).


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 ⩾1 episode of nausea/vomiting on treatment 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 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.


CONCLUSIONS
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.
Life-Course Nutrition and Health, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.
M E J
ME
Lean
Department of Endocrinology, University Hospital La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
R
R
Carraro
National Centre for Cardiovascular Prevention and Outcomes, UCL Institute of Cardiovascular Science, London, UK.
N
N
Finer
Novo Nordisk A/S, Søborg, Denmark.
H
H
Hartvig
Novo Nordisk A/S, Søborg, Denmark.
M L
ML
Lindegaard
Obesity Unit, Karolinska University Hospital Huddinge, Stockholm, Sweden.
S
S
Rössner
Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Antwerp, Belgium.
L
L
Van Gaal
Department of Nutrition, Exercise and Sports, Faculty of Sciences, University of Copenhagen, Frederiksberg, Denmark.
A
A
Astrup
D000293:Adolescent; D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005060:Europe / Q000453:epidemiology; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced* / Q000453:epidemiology; D009765:Obesity / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D011788:Quality of Life; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced* / Q000453:epidemiology; D015431:Weight Loss / Q000187:drug effects*
D019440:Anti-Obesity Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1