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Am Fam Physician. 2023;108(1):online

Clinical Question

Is a once-weekly injection of semaglutide a safe and effective way for adolescents with obesity to lose weight?

Bottom Line

Semaglutide helps adolescents lose a clinically significant amount of weight. It is unknown whether weight loss persists when the medication is discontinued, and there was a concerning increase in episodes of acute cholelithiasis, a known adverse effect of the drug. It is not clear whether the risk of acute cholelithiasis (also seen in a study of patients taking dulaglutide [Trulicity]) is caused by the medication or is a function of rapid weight loss. (Level of Evidence = 1b)


Semaglutide is a glucagon-like peptide-1 agonist that has been shown to help adults lose weight. The researchers recruited adolescents 12 to 17 years of age who were obese (i.e., body mass index [BMI] in the 95th percentile or higher) or overweight (i.e., BMI in the 85th percentile or higher) with at least one risk factor. After a 12-week run-in period, during which the 200 participants received lifestyle counseling, they were randomized in a 2:1 ratio to receive semaglutide subcutaneously once weekly or matching placebo. The dose started at 0.25 mg and was escalated as tolerated to a maximum dose of 2.4 mg during the first 16 weeks. The groups were balanced at the start of the study, and the analysis was by intention to treat. All participants and their families received lifestyle education throughout the trial. All but one participant were obese, with a mean pretreatment BMI of 37.7 in the semaglutide group and 35.7 in the placebo group. Only five patients were lost to follow-up or withdrew by the end of the 68-week trial. The primary outcome was a percentage change in BMI, which was significantly greater in the semaglutide group (−16.1% vs. 0.6%; P < .001). Significantly more patients in the semaglutide group had reductions in body weight of at least 5% (73% vs. 18%; number needed to treat [NNT] = 2), 10% (62% vs. 8%; NNT = 2), and 20% (37% vs. 3%; NNT = 3). Quality-of-life scores improved, especially in the physical comfort domain. Gastrointestinal symptoms were more common with semaglutide. Five patients in the treatment group had cholelithiasis (one also had cholecystitis) compared with none in the placebo group. Withdrawals due to adverse effects were similar between groups.

Study design: Randomized controlled trial (single-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Outpatient (any)

Reference: Weghuber D, Barrett T, Barrientos-Pérez M, et al.; STEP TEENS Investigators. Once-weekly semaglutide in adolescents with obesity. N Engl J Med. 2022;387(24):2245-2257.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell. 

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