Adolescent obesity is frequently accompanied by insulin resistance and multiple cardiometabolic abnormalities that may persist into adulthood. A secondary analysis of the STEP TEENS phase 3a randomized controlled trial, published in Diabetes Care, evaluated the effects of semaglutide  2.4 mg insulin sensitivity and cardiometabolic risk factors in adolescents with obesity. 

The analysis included 193 adolescents aged 12 to younger than 18 years without type 2 diabetes, including 129 participants assigned to once-weekly subcutaneous semaglutide 2.4 mg and 64 assigned to placebo. Changes from baseline to week 68 were evaluated across insulin sensitivity measures, glycemic parameters, lipid markers, liver enzymes, and anthropometric indices. 

Findings

• Fasting serum insulin levels decreased by 33.6% with semaglutide compared with 10.1% with placebo (P = 0.0012), while homeostatic model assessment for insulin resistance (HOMA-IR) scores declined by 35.0% versus 5.3%, respectively (P = 0.0002).
• Glycemic measures improved significantly with semaglutide, including glycated hemoglobin (P < 0.0001) and fasting plasma glucose (P = 0.0181).
• Alanine aminotransferase levels decreased by 17.9% with semaglutide compared with 3.3% with placebo (P = 0.0232).
• Waist-to-height ratio improved significantly with semaglutide treatment (P < 0.0001).
• Semaglutide was associated with greater reductions in triglycerides (P < 0.0001), low-density lipoprotein cholesterol (P = 0.0105), and total cholesterol (P < 0.0001) compared with placebo.
• Semaglutide was associated with greater reductions in triglycerides (P < 0.0001), low-density lipoprotein cholesterol (P = 0.0105), and total cholesterol (P < 0.0001) compared with placebo. 

Among adolescents with obesity, semaglutide 2.4 mg was associated with improvements in insulin sensitivity, glycemic measures, liver enzymes, and multiple cardiometabolic risk factors over 68 weeks. Greater metabolic improvements were observed in participants achieving larger BMI reductions.