ESPE Abstracts

Obesity in adolescents is associated with increased risk of prediabetes and type 2 diabetes (T2D) and long-term complications in adulthood. Data regarding the effects of anti-obesity medications on glycaemic outcomes in adolescents are sparse. STEP TEENS (NCT04102189), a phase 3a, double-blind, placebo-controlled randomised trial in adolescents 12 to <18 years of age with obesity demonstrated that once-weekly subcutaneous semaglutide 2.4 mg provided a greater percentage reduction in body mass index (BMI) than placebo from baseline to week 68.1 This STEP TEENS secondary analysis investigated the effect of semaglutide 2.4 mg compared to placebo on fasting plasma glucose (FPG), HbA1c, fasting insulin (FI) and homeostatic model assessment for insulin resistance (HOMA-IR) from baseline to week 68. Additionally, this analysis compared measures of glucose metabolism and insulin sensitivity in participants with ≥20% vs <20% reductions in BMI in the semaglutide 2.4 mg treatment arm. Analyses were performed with on-treatment assessments using mixed models for repeated measurements. P-values were not adjusted for multiple comparisons. Participants with T2D (n=8) were excluded. At week 68, participants receiving semaglutide (n=129) vs placebo (n=64) had greater reductions from baseline in FPG, (–0.22 mmol/L vs –0.02 mmol/L; estimated treatment difference [ETD] [95% confidence interval (CI)]: –0.20 [–0.35, –0.04]; P=0.0117), HbA1c, (–0.36%-points vs –0.14%-points; ETD [95% CI]: –0.22 [–0.30, –0.15]; P<0.0001), FI (–37.00% vs –8.67%; ETD [95% CI]: –31.02 [–42.88, –16.69]; P=0.0001) and HOMA-IR (–38.63% vs –5.84%; ETD [95% CI]: –34.83 [–47.31, –19.38]; P=0.0001). For semaglutide recipients, observed improvements in all endpoints were greater in those who achieved ≥20% vs <20% BMI reduction at week 68 (Table). Results were consistent when stratified by ≥20% (n=49) vs <20% (n=77) weight loss. Once-weekly semaglutide 2.4 mg compared to placebo provided significant improvements in glycaemic measures and insulin sensitivity in adolescents with obesity, with greater improvements in semaglutide recipients with ≥20% vs <20% BMI reduction.

Reference: Weghuber D, et al. Once-weekly semaglutide in adolescents with obesity. N Engl J Med. 2022;387:2245–57.