Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published December 14, 2022


Did treatment with semaglutide result in a greater reduction in BMI than lifestyle intervention alone in the trial by Weghuber et al.?

A once-weekly, 2.4-mg dose of subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, is used to treat obesity in adults, but assessment of the drug in adolescents has been lacking. Weghuber et al. conducted a trial that assessed the efficacy and safety of once-weekly subcutaneous semaglutide as compared with placebo (plus lifestyle intervention in both groups) among adolescents with obesity. Read the NEJM Original Article here.

Clinical Pearls

Q: How effective are lifestyle modifications for young people with obesity?

A: It is predicted that more than 250 million children and adolescents will have obesity by 2030. For young people, obesity-management guidelines recommend multimodal lifestyle modification. However, resulting reductions in body-mass index (BMI) are generally modest, and long-term weight maintenance is challenging and rarely achieved.

Q: What pharmacologic treatments are approved for use in adolescents with obesity?

A: Pharmacotherapy may be considered if lifestyle intervention alone is ineffective, but options are limited. The Food and Drug Administration has approved once-daily liraglutide (3.0 mg), orlistat (120 mg), and phentermine–topiramate (7.5 mg of phentermine with 46 mg of topiramate or 15 mg of phentermine with 92 mg of topiramate) for adolescents at least 12 years of age; only liraglutide is approved by the European Medicines Agency.

Morning Report Questions 

Q: Did treatment with semaglutide result in a greater reduction in BMI than lifestyle intervention alone in the trial by Weghuber et al.?

A: In this phase 3a trial involving adolescents with obesity who were randomly assigned to receive semaglutide or placebo, each with lifestyle intervention, once-weekly subcutaneous semaglutide at a dose of 2.4 mg resulted in clinically relevant decreases in BMI and body weight. The mean change in BMI from baseline to week 68 was −16.1% with semaglutide and 0.6% with placebo (estimated difference, −16.7 percentage points; 95% confidence interval [CI], −20.3 to −13.2; P<0.001). At week 68, a total of 95 of 131 participants (73%) in the semaglutide group had weight loss of 5% or more, as compared with 11 of 62 participants (18%) in the placebo group (estimated odds ratio, 14.0; 95% CI, 6.3 to 31.0; P<0.001). Reductions in body weight and improvement with respect to cardiometabolic risk factors (waist circumference and levels of glycated hemoglobin, lipids [except high-density lipoprotein cholesterol], and alanine aminotransferase) were greater with semaglutide than with placebo.

Q: What were some of the limitations of the trial by Weghuber et al.?

A: A longer treatment period would have provided insight into the durability of the effect of semaglutide; in adults, the effect of semaglutide persists over 2 years of treatment. A longer follow-up period would have enabled the effect of treatment cessation to be monitored. In addition, the enrolled trial population may limit the generalizability of the results, in light of the greater number of female than male participants, the relatively small proportions of some racial and ethnic groups, and the inclusion of only eight participants with type 2 diabetes and only one with overweight. It is possible that adolescents of the racial and ethnic groups that were underrepresented in this trial may have different responses to semaglutide, and future studies should address this issue.

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