Semaglutide gains FDA approval for treating obesity in adolescents aged ≥12 years

Semaglutide, a glucagon-like peptide-1 (GLP-1) analog that aids in weight loss by suppressing appetite, has recently gained approval from the United States (US) Food and Drug Administration (FDA) to treat obesity in children aged ≥12 years.1,2 The approval was based on the positive findings of a recent double-blinded, parallel-group, randomized, placebo-controlled study, which showed that semaglutide, coupled with lifestyle modification, could reduce body mass index (BMI) in adolescents with obesity when compared with lifestyle intervention alone.3

By 2030, obesity is expected to affect more than 250 million children and adolescents aged 5-19 years worldwide, making it a global health challenge.4 The situation is of great concern and has become a health burden of the society since obese children are at high risk of developing a number of medical conditions, such as type 2 diabetes (T2D), fatty liver disease (FLD), cardiovascular diseases (CVDs), sleep apnea, orthopedic problems, etc.5 Very often, obesity management starts with lifestyle modification, but it may not be sufficient for some patients who need pharmacotherapy for more intensive weight control.3 In 2021, a randomized, double-blind, placebo-controlled trial showed that weekly subcutaneous semaglutide achieved clinically relevant weight loss and improved cardiometabolic outcomes among adults with obesity.6 Nevertheless, its safety and efficacy among obese adolescents have yet to be evaluated in randomized trials.3

STEP TEENS was a randomized, double-blind placebo-controlled, parallel-group, multinational phase 3a trial conducted between October 2019 and March 2022 at 37 locations.3 Adolescents with obesity, defined as having a BMI in the ≥95th percentile, or with an overweight problem, defined as having a BMI in the ≥85th percentile, and with at least 1 weight-related coexisting condition were eligible.3 A total of 201 patients were enrolled and randomized 2:1 to receive either once-weekly subcutaneous semaglutide (n=134) or placebo (n=67), plus a lifestyle intervention for 68 weeks.3 The primary endpoint was the percentage change in BMI, and the secondary confirmatory endpoint was the reduction in ≥5% body weight from baseline to week 68.3 The trial was designed to test the superiority of semaglutide over placebo in terms of the primary and secondary endpoints.3 Additionally, cardiometabolic factors like waist circumference, blood pressure (BP), glycated hemoglobin (HbA1c) levels, total cholesterol (TC), low-density lipoprotein (LDL), very low-density lipoprotein cholesterol (VLDL), triglycerides (TG), and alanine aminotransferase (ALT) levels were also measured at week 68.3

At week 68, the mean percentage change in BMI was -16.1% in the semaglutide arm vs. 0.6% in the placebo arm (estimated difference=-16.7%; 95% CI: -20.3 to -13.2; p<0.001).3 Similarly, the secondary outcome favored the semaglutide group with 73% of the participants lost ≥5% of their body weight vs. only 18% in the placebo group (estimated odds ratio=14.0; 95% CI: 6.3-31.0; p<0.001).3 Additionally, semaglutide achieved greater improvements in cardiometabolic factors, including waist circumference, HbA1c levels (in all participants except those with T2D), lipids (except HDL-C), and ALT as compared with placebo.3

The rates of adverse events (AEs) were similar in the placebo group (82%) and the semaglutide group (79%).3 As to serious AEs, the rates were also similar between the 2 groups (11% in the semaglutide group and 9% in the placebo group).3 Of note, there were no fatal AEs.3 Gastrointestinal (GI) disorders, including primary nausea, vomiting, and diarrhea, were the most common AEs and were more frequent with semaglutide than with placebo (62% vs. 42%).3 However, these GI AEs were generally mild or moderate.3 Overall, semaglutide was well tolerated by adolescents with obesity and had a safety profile consistent with the findings among overweight or obese adults.3

In conclusion, when combined with lifestyle changes, the recently approved once-weekly subcutaneous semaglutide significantly reduces BMI in adolescents with obesity, providing an effective treatment option for this population who fail to achieve optimal weight control with lifestyle intervention alone.3

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