Effects of Semaglutide on BMI and Cardiometabolic Profile in Adolescents With Variants in Monogenic Obesity-Related Genes.

OBJECTIVES: To evaluate the impact of semaglutide on body mass index (BMI) and cardiometabolic markers in adolescents with obesity and genetic variants associated with monogenic or syndromic obesity. METHODS: A retrospective chart review was conducted in adolescents with severe obesity who underwent multigene panel testing and were treated with semaglutide. RESULTS: Twenty-seven adolescents (mean age 15 ± 1.9 years); BMI % of the 95th percentile 158 ± 29; (70% White) were treated with semaglutide for a mean of 10 ± 4.7 months. Participants were classified into three groups: (1) Dominant or Known Risk Variants (n = 7); (2) Carriers of Rare Variants in Recessive Genes (n = 10); and (3) Negative or Unmatched Genetic Findings (n = 10). All groups showed reductions in BMI, which was not different between the groups. Adolescents with dominant or known risk variants experienced a significant decrease in BMI % of the 95th percentile (-17, (IQR -26 to -10) p = 0.022) and in BMI by -9.4% ± 7% (p = 0.035). Significant improvements in median non-HDL cholesterol (-16 mg/dL), total cholesterol (-15 mg/dL), and HbA1c (-0.3%) were noted in children with dominant or known risk variants (p = 0.036). CONCLUSIONS: Semaglutide was associated with significant reductions in BMI and cardiometabolic markers in adolescents (majority White) with dominant or known risk variants for monogenic obesity.