Wegovy® (semaglutide) once weekly injection is a glucagon-like peptide 1 receptor agonist (GLP1-RA) approved by the FDA in June, 2021 for weight management in adults. Wegovy was approved in December, 2022 for children aged 12 and up with a BMI at the 95th% or above. This approval directly preceded the release of the first comprehensive guidelines on the evaluation and treatment of childhood obesity by the American Academy of Pediatrics (AAP).
Approval in pediatrics was based on a pivotal phase 3 trial published in The New England Journal of Medicine. Nearly 200 adolescents 12-18 years of age with a BMI of 95th% and higher or with a BMI of the 85th% or higher and at least one weight-related comorbid condition were enrolled. All participants completed a 12-week lifestyle intervention phase before randomization to once-weekly semaglutide (marching up to a dose of 2.4mg) or placebo. Most patients (90%) in the semaglutide group completed the trial, and the vast majority (87%) tolerated the highest dose.
The estimated mean percentage change in BMI from baseline to week 68, the endpoint of the trial, was 16.1% with semaglutide and 0.6% with placebo. Seventy-three percent of participants in the semaglutide group lost at least 5% of their body weight, compared to just 18% of the placebo group. A loss of body weight of at least 10% occurred in 62% of the participants in the semaglutide group, compared to 8% of placebo group, and a loss of at least 20% occurred in 37% and 3%, respectively. Improvement in metabolic risk factors such as waist circumference, ALT, A1C, and total cholesterol were greater amongst treatment group than placebo group. Gastrointestinal side effects, such as nausea, vomiting, and diarrhea were more common in semaglutide than placebo (62% vs. 42%) but were generally mild to moderate, and peaked during or shortly after the 16-week dose escalation period. Five participants (4%) in the semaglutide group had acute gallbladder disease while this did not occur in the placebo group. An increase in amylase and lipase levels were seen in the semaglutide group; however, there were no cases of pancreatitis observed. Serious adverse events were reported in 15 of 133 semaglutide participants (11%) and in 6 of 67 participants (9%) in the placebo group. There was an improvement in weight-related quality of life, mostly due to an improved physical comfort domain score. Interestingly, weight loss percentage was greater in the adolescent population in this trial than was reported in the Step1 trial in adults, potentially due to higher treatment completion rates in the trial.
The starting dose for Wegovy is 0.25 mg subcutaneous once weekly. The weekly dose is increased monthly until reaching the final dose of 2.4 mg – the dose is 0.5 mg for the second month, 1 mg for the third month, 1.7 mg for the fourth month, then 2.4 mg. Wegovy is contraindicated and should not be used in anyone with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
Reference:
Weghuber D, Barrett T, Barrientos-Pérez M, et al for the STEP TEENS Investigators. Once-Weekly Semaglutide in Adolescents with Obesity. N Engl J Med. 2022 Dec 15;387(24):2245-2257. PMID: 36322838.
Prepared by Emily Breidbart, MD, on behalf of the Drug & Therapeutics committee
Up to date as of 2/10/23