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Arslanian, S.* ; Gies, I.* ; Goldman, B.* ; Karlsson, T.* ; Kelly, A.S.* ; Skalshøi Kjær, M.* ; Körner, A. ; Noureddin, M.* ; Wabitsch, M.* ; Harder-Lauridsen, N.M.* ; Weghuber, D.*

Effect of semaglutide on insulin sensitivity and cardiometabolic risk factors in adolescents with obesity: The STEP TEENS study.

Diabetes Care:dc250824 (2025)

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OBJECTIVE: This secondary analysis of the Semaglutide Treatment Effect in People with obesity (STEP) TEENS (NCT04102189) study investigated the effect of semaglutide 2.4 mg versus placebo on insulin sensitivity and cardiometabolic risk factors. RESEARCH DESIGN AND METHODS: The STEP TEENS phase 3a randomized study in adolescents (aged 12 to <18 years) with obesity demonstrated that once-weekly subcutaneous semaglutide 2.4 mg provided a significantly greater percentage reduction in BMI than placebo at week 68 (estimated difference -16.7 percentage points; P = 0.0001). This analysis investigated changes in insulin sensitivity and cardiometabolic risk factors from baseline to week 68. RESULTS: Overall, 193 participants without type 2 diabetes were included in the analysis. Participants receiving semaglutide 2.4 mg (n = 129) compared with those receiving placebo (n = 64) had greater reductions from baseline in fasting serum insulin (-33.6% vs. -10.1%; P = 0.0012), homeostatic model assessment for insulin resistance (HOMA-IR) score (-35.0% vs. -5.3%; P = 0.0002), glycemic measures (glycated hemoglobin: P < 0.0001; fasting plasma glucose: P = 0.0181), alanine aminotransferase (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). Moreover, greater improvements in insulin sensitivity, glycemic measures, and cardiometabolic risk factors were seen in semaglutide 2.4 mg recipients with BMI reductions of ≥20% versus <20%. CONCLUSIONS: These novel data support semaglutide 2.4 mg as an efficacious obesity treatment in adolescents with obesity and advance its application by showing associated improvements in insulin sensitivity, glycemic measures, ALT, and other cardiometabolic risk factors.

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