Once-Weekly Semaglutide in Adolescents with Obesity

Abstract

Background: A once-weekly, 2.4-mg dose of subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, is used to treat obesity in adults, but assessment of the drug in adolescents has been lacking.

Methods: In this double-blind, parallel-group, randomized, placebo-controlled trial, we enrolled adolescents (12 to <18 years of age) with obesity (a body-mass index [BMI] in the 95th percentile or higher) or with overweight (a BMI in the 85th percentile or higher) and at least one weight-related coexisting condition. Participants were randomly assigned in a 2:1 ratio to receive once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo for 68 weeks, plus lifestyle intervention. The primary end point was the percentage change in BMI from baseline to week 68; the secondary confirmatory end point was weight loss of at least 5% at week 68.

Results: A total of 201 participants underwent randomization, and 180 (90%) completed treatment. All but one of the participants had obesity. The mean change in BMI from baseline to week 68 was -16.1% with semaglutide and 0.6% with placebo (estimated difference, -16.7 percentage points; 95% confidence interval [CI], -20.3 to -13.2; P<0.001). At week 68, a total of 95 of 131 participants (73%) in the semaglutide group had weight loss of 5% or more, as compared with 11 of 62 participants (18%) in the placebo group (estimated odds ratio, 14.0; 95% CI, 6.3 to 31.0; P<0.001). Reductions in body weight and improvement with respect to cardiometabolic risk factors (waist circumference and levels of glycated hemoglobin, lipids [except high-density lipoprotein cholesterol], and alanine aminotransferase) were greater with semaglutide than with placebo. The incidence of gastrointestinal adverse events was greater with semaglutide than with placebo (62% vs. 42%). Five participants (4%) in the semaglutide group and no participants in the placebo group had cholelithiasis. Serious adverse events were reported in 15 of 133 participants (11%) in the semaglutide group and in 6 of 67 participants (9%) in the placebo group.

Conclusions: Among adolescents with obesity, once-weekly treatment with a 2.4-mg dose of semaglutide plus lifestyle intervention resulted in a greater reduction in BMI than lifestyle intervention alone. (Funded by Novo Nordisk; STEP TEENS ClinicalTrials.gov number, NCT04102189.).

Figure 1 (facing page).. BMI and Body-Weight Measures in the Full Analysis Population.

The full analysis population included all participants who had undergone randomization. Data shown are the observed data from the in-trial observation period (the time from randomization to the last contact with a trial site, regardless of discontinuation of semaglutide or placebo or the use of rescue interventions [i.e., other medications for obesity or bariatric surgery]), unless otherwise indicated. Panel A shows the observed mean percentage change from baseline in body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) over time. The area to the right of the vertical dashed line represents the follow-up period, when participants were not receiving semaglutide or placebo. Panel B shows the observed percentages of participants who had body-weight reductions of at least 5%, at least 10%, at least 15%, and at least 20% from baseline to week 68. Panels C and D show waterfall plots of the observed mean percentage change in BMI from baseline to week 68 in the semaglutide group and the placebo group, respectively. Panels E and F show the observed mean BMI and body weight over time. The I bars in panels A, E, and F indicate the standard errors, and the numbers shown beneath the graphs are the participants contributing to the mean at each visit.