Objective: Liraglutide, a once-daily human glucagon-like peptide-1 analog, induced clinically meaningful weight loss in a phase 2 study in obese individuals without diabetes. The present randomized phase 3 trial assessed the efficacy of liraglutide in maintaining weight loss achieved with a low-calorie diet (LCD).
Methods: Obese/overweight participants (≥18 years, body mass index ≥30 kg m(-2) or ≥27 kg m(-2) with comorbidities) who lost ≥5% of initial weight during a LCD run-in were randomly assigned to liraglutide 3.0 mg per day or placebo (subcutaneous administration) for 56 weeks. Diet and exercise counseling were provided throughout the trial. Co-primary end points were percentage weight change from randomization, the proportion of participants that maintained the initial ≥5% weight loss, and the proportion that lost ≥5% of randomization weight (intention-to-treat analysis). ClinicalTrials.gov identifier: NCT00781937.
Results: Participants (n=422) lost a mean 6.0% (s.d. 0.9) of screening weight during run-in. From randomization to week 56, weight decreased an additional mean 6.2% (s.d. 7.3) with liraglutide and 0.2% (s.d. 7.0) with placebo (estimated difference -6.1% (95% class intervals -7.5 to -4.6), P<0.0001). More participants receiving liraglutide (81.4%) maintained the ≥5% run-in weight loss, compared with those receiving placebo (48.9%) (estimated odds ratio 4.8 (3.0; 7.7), P<0.0001), and 50.5% versus 21.8% of participants lost ≥5% of randomization weight (estimated odds ratio 3.9 (2.4; 6.1), P<0.0001). Liraglutide produced small but statistically significant improvements in several cardiometabolic risk factors compared with placebo. Gastrointestinal (GI) disorders were reported more frequently with liraglutide than placebo, but most events were transient, and mild or moderate in severity.
Conclusion: Liraglutide, with diet and exercise, maintained weight loss achieved by caloric restriction and induced further weight loss over 56 weeks. Improvements in some cardiovascular disease-risk factors were also observed. Liraglutide, prescribed as 3.0 mg per day, holds promise for improving the maintenance of lost weight.