The findings are from a secondary analysis of the Semaglutide Treatment Effect in People with obesity (STEP) TEENS trial, led by Silva Arslanian from the Division of Pediatric Endocrinology, Diabetes, and Metabolism at UPMC Children’s Hospital of Pittsburgh, along with colleagues. While the primary results of STEP TEENS previously demonstrated substantial reductions in body mass index (BMI) with semaglutide, this analysis focused on metabolic outcomes that are closely linked to future cardiometabolic disease risk.
STEP TEENS was a phase 3a randomized, placebo-controlled study that enrolled adolescents aged 12 to 18 years with obesity. Participants received once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks, alongside lifestyle intervention. The original trial showed that semaglutide produced a significantly greater reduction in BMI compared with placebo, with an estimated difference of nearly 17 percentage points by the end of the study period.
In the current analysis, 193 participants without type 2 diabetes were included, with 129 receiving semaglutide and 64 receiving a placebo. Changes in insulin sensitivity and cardiometabolic risk markers from baseline to week 68 were evaluated.
The study revealed the following findings:
- Adolescents receiving semaglutide showed significantly greater improvements in multiple metabolic parameters compared with those given a placebo.
- Fasting serum insulin levels decreased markedly in the semaglutide group.
- Insulin resistance, assessed by HOMA-IR, was substantially reduced with semaglutide treatment.
- Glycemic control improved, with significant reductions in glycated hemoglobin and fasting plasma glucose.
- Semaglutide led to greater reductions in alanine aminotransferase levels.
- Improvements were observed in the waist-to-height ratio among adolescents treated with semaglutide.
- Lipid profiles improved with semaglutide, including significant decreases in triglycerides, LDL cholesterol, and total cholesterol.
- Greater metabolic benefits were seen in adolescents who achieved a BMI reduction of at least 20%.
- Larger BMI reductions were associated with more pronounced improvements in insulin sensitivity, glycemic measures, and cardiometabolic risk factors.
The authors note that these results extend the clinical relevance of semaglutide beyond weight loss alone. By demonstrating improvements in insulin sensitivity, glucose metabolism, liver enzymes, and lipid parameters, the study supports the broader metabolic benefits of semaglutide in adolescents with obesity.
Overall, the secondary analysis reinforces semaglutide 2.4 mg as an effective treatment option for adolescent obesity and suggests that its use may help reduce early cardiometabolic risk, potentially altering long-term health trajectories in this vulnerable population.
Reference:
Silva Arslanian, Inge Gies, Bryan Goldman, Tobias Karlsson, Aaron S. Kelly, Mette Skalshøi Kjær, Antje Körner, Mazen Noureddin, Martin Wabitsch, Nina M. Harder-Lauridsen, Daniel Weghuber; Effect of Semaglutide on Insulin Sensitivity and Cardiometabolic Risk Factors in Adolescents With Obesity: The STEP TEENS Study. Diabetes Care 2025; dc250824. https://doi.org/10.2337/dc25-0824
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