In adolescents with overweight or obesity, the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide in a new study was associated with a mean weight loss of 16.1% at 68 weeks, with nearly three-quarters of the study population losing ≥5% of their baseline body weight.
The findings, from the international phase 3 STEP TEENS clinical trial, could potentially expand the use of semaglutide 2.4 mg, approved in 2021 (Wegovy, Novo Nordisk) as an adjunct to diet and exercise for weight loss in adults, to the rapidly growing population of youth reaching body mass index (BMI) levels of ≥30 kg/m2.
“The results are amazing,” said senior STEP TEENS investigator Silva Arslanian, MD, professor of pediatrics and clinical and translational science and the Richard L. Day Endowed Chair in Pediatrics at the University of Pittsburgh School of Medicine, in a University statement. “For a person who is 5 foot, 5 inches tall and weighs 240 pounds, the average reduction in BMI equates to shedding about 40 pounds.”
As obesity rates increase worldwide, Arslanian added, it is no longer enough to advise people with weight issues to eat more vegetables and cut out sugar and fat. “We live in a very obesogenic environment, so it can be very hard to make those changes. There is a real need for safe and effective medications to treat obesity.”
The study, published online in the New England Journal of Medicine on November 2, and presented at ObesityWeek® 2022, November 1-4, enrolled adolescents aged 12 to <18 years with obesity (BMI in the 95th percentile or higher) or with overweight (BMI in the 85th percentile or higher) and at least one weight-related comorbidity. The trial recruited participants at 37 international locations between October 2019 and March 2022.
Arslanian and colleagues randomized the final cohort of 201 participants in a 2:1 ratio to receive once-weekly subcutaneous semaglutide 2.4 mg (n=234) or placebo (n=67) for 68 weeks. All participants participated in a 12-week lifestyle intervention phase just prior to randomization that included nutrition counseling and physical activity for weight loss. The investigators identified percentage change in BMI from baseline to week 68 as the study’s primary endpoint and weight loss of at least 5% at week 68 as a secondary confirmatory endpoint.
Of the 201 participants, 38% were boys, 36% were aged <15 years (mean age 15.4 years), and 79% were White. All but 1 of the youths were classified as having obesity. The research team reports that body weight, BMI, and waist circumference were slightly higher among those randomized to semaglutide, but other baseline characteristics were similar between groups.
At the end of the 68-week study period, the observed mean change in BMI from baseline was
-16.1% among those receiving semaglutide 2.4 mg and 0.6% among those receiving placebo (estimated difference, -16.7 percentage points [95% CI, -20.3 to -13.2]; P <.001).
Analysis of the secondary endpoint found that 73% of the adolescents receiving semaglutide 2.4 mg achieved weight loss of ≥5% compared to just 18% of those randomized to placebo (OR, 14.0 [95% CI, 6.3 to 31.0]; P <.001).
Additional weight reduction outcomes included a loss of ≥20% among 37% of youth in the semaglutide arm compared with 3% of those in the placebo arm.
Among improvements in cardiometabolic risk factors associated semaglutide use vs placebo treatment at week 68 were reductions in waist circumference, levels of glycated hemoglobin, lipids, and alanine aminotransferase. Based on analysis of responses to the Impact of Weight on Quality of Life—Kids questionnaire, youth who received semaglutide had improved scores at week 68 which authors say was mainly the result of improvements in the domain of physical comfort. Arslanian et al note that semaglutide is the first antiobesity medication to be linked with such quality-of-life improvements in adolescents.
The safety analysis found a higher incidence of gastrointestinal adverse events with semaglutide than with placebo (62% vs 42%) and 4 cases of cholelithiasis among adolescents randomized to semaglutide. Serious adverse events, investigators say, were reported among 11% of the semaglutide group and 9% of the placebo group. The safety and tolerability outcomes were consistent with adult phase 3 semaglutide data and with the GLP-1 RA class.
Speaking during a panel discussion during ObesityWeek® 2022 where the study was presented, 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 “These results are mind-blowing in summary. 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.”
Reference: Weghuber D, Barrett T, Barrientos-Perez M, et al, for the STEP TEENS Investigators. Once-weekly semaglutide in adolescents with obesity. New Engl J Med. Published online November 2, 2022. doi:10.1056/NEJMoa2208601