Investigators from multiple institutions conducted a randomized, double blind, placebo-controlled trial to assess the efficacy and safety of liraglutide, a glucagon-like peptide analogue that increases postprandial insulin, reduces glucagon secretion, and delays gastric emptying, in adolescents with obesity. Children aged 12–17 years were enrolled at 32 sites in 5 countries (Belgium, Mexico, Russia, Sweden, and the United States). Children were eligible if they had a BMI ≥30, a weight change of <5 kg in the previous 90 days, and a poor response to lifestyle therapy alone. Participants were randomly assigned in a 1:1 ratio to the intervention or placebo group. Intervention participants received 12 weeks of lifestyle therapy followed by 56 weeks of liraglutide subcutaneously at a dose of 0.6 mg once daily for 1 week, which was increased weekly until the maximum tolerated dose or the highest dose allowed of 3.0 mg. Placebo participants received 12 weeks of lifestyle therapy followed by 56 weeks of a volume-matched placebo administered subcutaneously once daily.
The primary outcome was the change from baseline at week 56 in the BMI standard deviation score, a measure of the number of standard deviations from the population mean BMI, matched for age and sex. Secondary outcomes included a change from baseline in BMI and adverse events during the treatment period. Investigators assessed the effect of allocation group on outcomes according to the intention-to-treat principle.
There were 125 participants in the intervention group and 126 in the placebo group; 80.8% and 79.4% intervention and placebo participants, respectively, completed treatment through week 56. Among intervention participants, 82.4% reached the maximal 3.0 mg dose.
The change from baseline in BMI standard deviation score was greater in the intervention group than placebo group (treatment difference, −0.22; 95% CI, −0.37, −0.08). There also was a greater relative change in BMI among intervention participants than placebo participants (treatment difference, −4.64; 95% CI, −7.14, −2.14). There was no difference in the proportion of participants who reported adverse events in the intervention (88.8%) and placebo (84.9%) groups. However, gastrointestinal events (nausea, vomiting, and diarrhea) were reported by more intervention than placebo participants (64.8% vs 36.5%, respectively; P < .001). Discontinuation of the trial because of adverse events also occurred in more intervention than placebo participants (13 vs 0 participants, respectively; P < .001).
The authors conclude that liraglutide plus lifestyle therapy is superior to placebo plus lifestyle therapy in reduction of BMI in adolescents with obesity.
Drs Wong and Armstrong have disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
Despite decades of research and public health advocacy to reduce pediatric obesity, prevalence continues to increase.1 In adults, pharmacologic options have expanded in the last several years...