November 02, 2022
4 min read
Weghuber D. O-020. Presented at: ObesityWeek; Nov. 1-4, 2022; San Diego.
Weghuber reports serving as a consultant for Novo Nordisk. Please see the study for all other authors’ relevant financial disclosures.
SAN DIEGO — Adolescents with obesity had a BMI reduction of 16.1% at 68 weeks with once-weekly subcutaneous semaglutide 2.4 mg plus lifestyle intervention, results similar to those seen with adults, according to top-line results presented at ObesityWeek 2022.
In findings from the STEP TEENS phase 3a trial, adolescents aged 12 to 17 years with obesity or overweight and at least one weight-related coexisting condition were randomly assigned 2:1 to receive semaglutide 2.4 mg (Wegovy, Novo Nordisk) or placebo for 68 weeks. At the end of the trial, 73% of adolescents in the semaglutide group had a reduction in body weight of 5% or greater compared with 18% of those in the placebo group.
“Semaglutide 2.4 mg was superior to placebo with respect to percent change in BMI and 5% body weight responders at week 68,” Daniel Weghuber, MD, professor of pediatrics at Paracelsus Medical School in Salzburg, Austria, said during a presentation. “Improvements were also seen in all other weight-related parameters, cardiovascular risk factors and glucose metabolism.”
The trial took place at 37 sites in multiple countries from October 2019 through March 2022. Researchers enrolled 201 adolescents with a BMI in the 95th percentile or higher according to sex- and age-specific growth charts, or a BMI in the 85th percentile or higher with at least one weight-related coexisting condition (62% girls; mean age, 15.4 years; 79% white). Only one participant in the study fit the second criteria for overweight.
Adolescents entered a 12-week lifestyle intervention run-in phase after screening. After the run-in phase concluded, participants were randomly assigned to receive weekly subcutaneous semaglutide 2.4 mg (n = 134) or matching placebo (n = 67) for 68 weeks. Following the treatment period was a 7-week follow-up in which participants did not receive semaglutide or placebo. Lifestyle therapy consisting of nutrition counseling and physical activity for weight loss was provided for both groups. The primary endpoint was the change in BMI from baseline to 68, weeks and the secondary endpoint was the proportion of participants with a 5% or greater reduction in body weight. Cardiometabolic risk factors were assessed at baseline at 68 weeks. The Impact of Weight on Quality of Life–Kids questionnaire was conducted to assess quality of life.
The findings were simultaneously published in The New England Journal of Medicine.
Greater weight loss observed with semaglutide
From baseline to week 68, the semaglutide group had a 16.1% reduction in BMI compared with a 0.6% increase in BMI for the placebo group (P < .001). After the 7-week follow-up period, the semaglutide group still had a 13.2% lower BMI compared with baseline, whereas the BMI increase in the placebo group went up to 1.2%.
At week 68, 73% of the semaglutide group had a 5% or greater body weight loss from baseline compared with 18% of the placebo group (P < .001).
The semaglutide group had a significantly lower waist circumference, HbA1c for those without type 2 diabetes, total cholesterol, LDL cholesterol, triglycerides and alanine transaminase compared with placebo at 68 weeks. Blood pressure and HDL cholesterol were similar between the two groups. Adolescents receiving semaglutide had improvements in quality of life score at week 68 compared with baseline, with the improvement driven by a better score in the physical comfort domain.
Adverse events were reported by 79% of participants receiving semaglutide and 82% receiving placebo. Gastrointestinal disorders were reported by 62% of the semaglutide group and 42% of the placebo group. Adverse events were mostly mild or moderate in severity and of short duration, according to the researchers. Serious adverse events were reported by 11% in the semaglutide group and 9% in the placebo group. Five participants in the semaglutide group had acute gallbladder disease compared with none in the placebo group.
“Safety and tolerability were consistent with adult phase 3 data and GLP-1 receptor agonists in general,” Weghuber said.
Semaglutide may begin “new era” for pediatric obesity treatment
During a panel discussion following the presentation, experts stated that semaglutide could change the landscape of pediatric obesity treatment. Weghuber compared the findings from STEP TEENS with those found in SCALE TEENS, a trial in which adolescents with obesity were randomly assigned to 3.0 mg of liraglutide (Saxenda, Novo Nordisk) or placebo. In SCALE TEENS, the group receiving liragludtide had an estimated treatment difference in BMI of 5.01% compared with placebo, whereas the estimated treatment difference in STEP TEENS between the semaglutide and placebo groups was 16.7%.
Claudia Fox, MD, MPH, associate professor in the department of pediatrics and co-director for pediatric obesity medicine at the University of Minnesota Medical School, said the level of BMI reduction in the semaglutide group was close to that seen with bariatric surgery. She also noted the improvement in quality of life will be meaningful for families.
“These results are mind-blowing in summary,” Fox said during the panel discussion. “I think we really are at the doorstep of a new era in terms of how we are now going to be able to really effectively treat adolescent and pediatric patients with obesity.”
Sarah Armstrong, MD, professor of pediatrics and population health science at Duke University School of Medicine, echoed Fox’s comments while adding that it is crucial for providers to think ahead when treating adolescents with obesity and to produce a gameplan for how to maintain weight loss.
“I do want us all to think about what’s next,” Armstrong said during the panel discussion. “After we’ve really helped them in such a profound way, how can we help support them?”
- Weghuber D, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2208601.