In a placebo-controlled trial, semaglutide recipients had a mean 16% decrease in body mass index.

Glucagon-like peptide-1 (GLP-1) receptor agonists lower weight in obese adults, and one such drug (liraglutide) is also US FDA approved for adolescents. Now, in an industry-sponsored trial, 201 adolescents (age range, 12 to 17 years) with body mass index (BMI) 95th percentile or higher (mean BMI, 37kg/m²) were randomised to receive weekly injections of the GLP-1 agonist semaglutide or placebo for 68 weeks, along with behavioural lifestyle therapy.

Mean changes in BMI at 68 weeks were −16.1% in the semaglutide group and +0.6% in the placebo group. The semaglutide group also had reductions in cardiometabolic risk factors, including weight, waist circumference, glycated haemoglobin level and lipid levels. Gastrointestinal adverse effects classified as ‘nonserious’ (e.g. nausea, vomiting, abdominal pain) were more common with semaglutide than with placebo (62% vs 42%). Additionally, five semaglutide recipients and no placebo recipients developed acute gallbladder disease. In the seven weeks after cessation of treatment, BMI increased significantly in the semaglutide group.

Comment: Injected semaglutide lowered weight in teenagers with obesity. Although semaglutide is not yet FDA approved for adolescents, some paediatricians and adolescent medicine experts probably believe sufficient evidence already exists to use GLP-1 agonists liberally in these patients. However, I worry about the adverse gastrointestinal effects and the durability of weight loss after stopping injections. I would consider prolonged drug therapy only if evidence eventually demonstrates that it is both safe and effective. Ideally, a short-term course of semaglutide would be accompanied by healthy lifestyle changes that maintain weight reduction after the drug is stopped, but that goal is often elusive.

JAMES A. FEINSTEIN, MD, MPH
Associate Professor of Pediatrics, Children’s Hospital Colorado and University of Colorado School of Medicine, Denver, USA.

Weghuber D, et al. Once-weekly semaglutide in adolescents with obesity. N Engl J Med 2022; 387: 2245-2257.

This summary is taken from the following Journal Watch title: Pediatrics and Adolescent Medicine