Effect of Semaglutide on Insulin Sensitivity and Cardiometabolic Risk Factors in Adolescents With Obesity: The STEP TEENS Study

Semaglutide 2.4 mg once weekly improved insulin sensitivity and several cardiometabolic risk factors in adolescents with obesity, compared with placebo, over 68 weeks. This secondary analysis of the STEP TEENS trial measured changes in fasting insulin, HOMA-IR, glycemic measures, liver enzyme ALT, and lipid and abdominal obesity markers, with the greatest benefits seen in those who lost the most BMI.

Late-phase clinical trial — Secondary analysis of phase 3a randomised trial. Population: adolescents aged 12 to <18 years with obesity and without type 2 diabetes. Sample size: 193 participants. Follow-up: 68 weeks. Interventions: semaglutide 2.4 mg once weekly subcutaneous. Cited by 2 other papers.

Among 193 adolescents with obesity but no type 2 diabetes, semaglutide produced greater reductions than placebo in fasting serum insulin (-33.6% vs -10.1%; P=0.0012) and HOMA-IR (-35.0% vs -5.3%; P=0.0002). Glycated hemoglobin (P<0.0001), fasting plasma glucose (P=0.0181), ALT (-17.9% vs -3.3%; P=0.0232), waist-to-height ratio (P<0.0001), triglycerides (P<0.0001), LDL cholesterol (P=0.0105), and total cholesterol (P<0.0001) all improved more with semaglutide. The underlying trial also found a greater percentage BMI reduction with semaglutide than placebo (estimated difference -16.7 percentage points; P=0.0001).

This paper matters to Semaglutide researchers because it extends the STEP TEENS BMI findings to insulin sensitivity and multiple cardiometabolic risk factors in adolescents. It does not establish whether these metabolic improvements are independent of weight loss or persist long-term, and it excludes adolescents with type 2 diabetes.

Key findings

• Semaglutide reduced fasting serum insulin by 33.6% versus 10.1% with placebo (P=0.0012).
• HOMA-IR fell 35.0% with semaglutide versus 5.3% with placebo (P=0.0002).
• Alanine aminotransferase decreased 17.9% with semaglutide versus 3.3% with placebo (P=0.0232).
• The underlying trial found a greater percentage BMI reduction with semaglutide than placebo (estimated difference -16.7 percentage points; P=0.0001).
• Greater improvements in insulin sensitivity and cardiometabolic risk factors were seen in semaglutide recipients with BMI reductions of ≥20% versus <20%.

Limitations

• Authors did not state limitations in the abstract.
• This is a secondary analysis of a trial designed primarily to assess BMI rather than insulin sensitivity.
• Adolescents with type 2 diabetes were excluded, so results may not generalise to that group.
• Insulin sensitivity was estimated using HOMA-IR, a surrogate measure, rather than measured directly.

The record

• Journal: Diabetes care 49(6): 954-962
• Published: 2026-05-25
• PMID: 41296499 — DOI: 10.2337/dc25-0824
• MeSH terms: Humans, Insulin Resistance, Obesity, Blood Glucose, Risk Factors, Adolescent, Child, Female, Male, Glucagon-Like Peptides, Cardiometabolic Risk Factors
• Funding: Novo Nordisk A/S
• Author countries: Austria, Belgium, Denmark, Germany

Peptide profiles: Semaglutide.

All indexed evidence: Semaglutide trials & papers.

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