Weight gain after weight loss is a major problem in treating those with obesity.


Adults with obesity (body mass index) were included in a randomized, placebo-controlled head-to-head study [the weight in kilograms divided by the square of the height in meters], 32 to 43) who did not have diabetes. After an 8 week low calorie diet, participants were randomly assigned to one of four strategies for 1 year: a moderate to vigorous intensity exercise program plus placebo (exercise group); Treatment with liraglutide (3.0 mg per day) plus usual activity (liraglutide group); Exercise program plus liraglutide therapy (combination group); or placebo plus usual activity (placebo group). Endpoints with predefined hypotheses were the change in body weight (primary endpoint) and the change in body fat percentage (secondary endpoint) from randomization to the end of the treatment period in the population to be treated. Pre-established health endpoints and metabolic safety were also assessed.


After the 8-week low-calorie diet, 195 participants had an average decrease in body weight of 13.1 kg. After 1 year, all active treatment strategies resulted in greater weight loss than placebo: Difference in exercise group: -4.1 kg (95% confidence interval) [CI]-7.8 to -0.4; P = 0.03); in the liraglutide group -6.8 kg (95% CI, -10.4 to -3.1; P <0.001); and in the combination group -9.5 kg (95% CI, -13.1 to -5.9; P <0.001). The combination strategy resulted in greater weight loss than during exercise (difference –5.4 kg; 95% CI –9.0 to –1.7; P = 0.004), but not liraglutide (–2.7 kg; 95% CI -6.3 to 0.8; P = 0.13). The combination strategy reduced the body fat percentage by 3.9 percentage points, which is roughly twice the decrease in the exercise group (-1.7 percentage points; 95% CI, -3.2 to -0.2; P = 0.02) and the liraglutide group ( –1.9) corresponds to percentage points; 95% CI, -3.3 to -0.5; P = 0.009). Only the combination strategy was associated with improvements in glycated hemoglobin levels, insulin sensitivity, and cardiorespiratory fitness. Increased heart rate and cholelithiasis were observed more frequently in the liraglutide group than in the combination group.


A strategy that combined exercise and liraglutide therapy improved maintenance of healthy weight loss more than any treatment alone. (Funded by the Novo Nordisk Foundation and others; EudraCT number, 2015-005585-32;; ClinicalTrials.gov number, NCT04122716.)