1. In adolescents with obesity, semaglutide plus lifestyle intervention resulted in a significant body mass index (BMI) reduction compared to lifestyle intervention alone.

2. The semaglutide group had a greater reduction in waist circumference and levels of glycated hemoglobin compared to lifestyle intervention alone. 

Evidence Rating Level: 1 (Excellent)

Study Rundown: For adolescents with obesity, multimodal lifestyle modification is typically recommended. Though, associated reductions in BMI are generally modest. Pharmacotherapy can be considered, but options are limited. Semaglutide is a glucagon-like peptide 1 (GLP1) agonist that induces weight loss by decreasing appetite, thereby improving control of eating and reducing energy intake. Semaglutide is approved for long-term weight management as an adjunct to a reduced-calorie diet and increased physical activity for adults with obesity or for adults with overweight who have weight-related coexisting conditions. However, there is a gap in knowledge as to understanding whether once-weekly semaglutide plus lifestyle intervention is effective among adolescents with obesity. Overall, this study found that in adolescents with obesity, once-weekly semaglutide in addition to a lifestyle intervention resulted in a substantial reduction in BMI as compared with lifestyle intervention alone. This study has limited generalizability, as there were relatively small proportions of some racial and ethnic groups, and eight participants with type 2 diabetes, which may not be representative of the adolescent population in the United States. Nevertheless, the study’s findings demonstrate that once-weekly semaglutide provides a significant reduction in BMI compared with lifestyle modification alone.

Click to read the study in NEJM

Relevant Reading: Weight and Health — Pathophysiology and Therapies

In-Depth [randomized controlled trial]: This double-blind, randomized, placebo-controlled clinical trial was conducted from October 2019 through March 2022. Patients who were adolescents (12 to 17 years of age) with a BMI in the 95th percentile or higher (according to sex and age-specific growth charts) and those with a BMI in the 85th percentile or higher who had at least one weight-related coexisting condition with at least one unsuccessful dietary weight loss effort were eligible for the study. Patients who had a weight change of more than 5kg, previous bariatric surgery, uncontrolled thyroid disease, secondary cause of obesity, major depressive disorder within two years, diagnosis of severe psychiatric disorders, and history of suicide attempt were excluded from the study. The primary outcome measured was the percentage change in BMI. Outcomes in the primary analysis were assessed via efficacy analysis and two-sided 95% Confidence Intervals [CI]. Based on the primary analysis, the mean change in BMI from baseline to week 68 was −16.1% with semaglutide and 0.6% with placebo (estimated difference, −16.7%; 95% CI, −20.3 to −13.2). At week 68, 73% of the semaglutide group reported weight loss of 5% or more, as compared to 18% of the placebo group (estimated odds ratio, 14.0; 95% CI, 6.3 to 31.0). Reductions in body weight and improvement with respect to cardiometabolic risk factors (waist circumference and levels of glycated hemoglobin, lipids, and alanine aminotransferase) were greater with semaglutide than with placebo. Overall, this study demonstrates that once-weekly treatment of a 2.4mg dose of semaglutide plus lifestyle intervention resulted in a greater BMI reduction than lifestyle intervention alone in adolescents with obesity.

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