Once-weekly treatment with semaglutide 2.4 mg in adolescents with obesity, along with lifestyle intervention, is associated with a substantial reduction in body mass index (BMI) compared with the use of lifestyle intervention alone, according to study findings that were published in The New England Journal of Medicine.
Investigators conducted the STEP TEENS trial (Semaglutide Treatment Effect in People with Obesity TEENS; ClinicalTrials.gov Identifier: NCT04102189), a double-blind, parallel-group, randomized, placebo-controlled trial. This multinational, phase 3a clinical trial took place at 37 sites between October 2019 and March 2022. After screening, all participants entered a 12-week lifestyle intervention run-in phase based on regulatory guidelines. After the end of the run-in phase (baseline), eligible participants were randomly assigned in a 2:1 ratio to treatment with once-weekly subcutaneous semaglutide 2.4 mg or matching placebo for 68 weeks. This treatment period was followed by a 7-week follow-up period in which none of the participants received either semaglutide or placebo.
Randomization was conducted with use of an interactive Web-response system, with stratification based on sex and pubertal status (Tanner stage 2 or 3 vs Tanner stage 4 or Tanner stage 5). The semaglutide dose was escalated over 16 weeks from 0.25 mg to 2.4 mg or to the maximum dose that was not associated with unacceptable adverse events (AEs).
All of the participants and their parents or guardians received behavioral lifestyle therapy, which was defined as counseling about healthy nutrition and physical activity for weight loss throughout the trial.
In the run-in phase, all eligible participants comprised adolescents aged 12 to 18 years with a BMI in the 95th percentile or higher. Those with a BMI in the 85th percentile or higher and 1 or more weight-related coexisting condition were eligible as well. All participants needed to have completed 1 or more unsuccessful dietary weight-loss effort. The same BMI criteria were used to determine eligibility for study randomization. Any individual who completed the run-in phase but did not fulfill the BMI randomization criteria was considered ineligible at screening.
The primary study endpoint was the percentage change in BMI from baseline to week 68. The secondary confirmatory endpoint was reduction in body weight of 5% or more at week 68. A total of 201 individuals were randomly assigned, with 90% of them completing the treatment. All but 1 of the participants had obesity. Overall, 62% of the participants were girls and 79% were White. The mean participant age was 15.4 years, the mean body weight was 107.5 kg, and the mean BMI was 37.
Results of the study showed that the mean change in BMI from baseline to week 68 was -16.1% with semaglutide vs 0.6% with placebo (estimated difference, -16.7 percentage points; 95% CI, -20.3 to -13.2; P <.001). At 68 weeks, 73% of the participants in the semaglutide group experienced weight loss of 5% or more, compared with 18% of those treated with placebo (estimated odds ratio, 14.0; 95% CI, 6.3-31.0; P <.001).
Reduction in body weight and improvement in cardiometabolic risk factors were all greater with semaglutide compared with placebo.
The incidence of gastrointestinal AEs was higher with semaglutide than with placebo (62% vs 42%, respectively). Overall, 5 individuals in the semaglutide arm and no participants in the placebo arm had cholelithiasis. Serious AEs occurred in 11% of participants in the semaglutide group vs 9% of those in the placebo group.
Limitations of the study include the short treatment period and follow-up period. Additionally, the enrolled trial population might limit the generalizability of the results, given the higher number of female participants, the relatively small proportions of certain racial and ethnic groups, and the inclusion of only 8 participants with type 2 diabetes and only 1 who was overweight.
“In adolescents with obesity, once-weekly treatment with subcutaneous semaglutide at a dose of 2.4 mg in addition to lifestyle intervention resulted in a substantial reduction in BMI as compared with lifestyle intervention alone,” the study authors wrote.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Weghuber D, Barrett T, Barrientos-Pérez M, et al; on behalf of the STEP TEENS investigators. Once-weekly semaglutide in adolescents with obesity. N Engl J Med. Published online November 2, 2022. doi:10.1056/NEJMoa2208601