Diabetes CareWeight LossRCTNovember 26, 2025

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

Arslanian S, Gies I, Goldman B, Karlsson T, Kelly AS, Skalshøi Kjær M, Körner A, Noureddin M, Wabitsch M, Harder-Lauridsen NM, Weghuber D

View on PubMed DOI: pii: dc250824. 10.2337/dc25-0824

Key Finding

Semaglutide helped obese teens lose 16.7 percentage points more BMI than placebo while dramatically improving insulin sensitivity by 35% and multiple heart health markers over 68 weeks.

What This Study Found

This study followed 193 obese teenagers for over a year, giving them either semaglutide (the same drug in Ozempic/Wegovy) or a fake shot. Think of insulin resistance like a key that doesn't fit the lock properly - your body makes more and more insulin trying to get sugar into cells, but it's inefficient. Semaglutide acted like WD-40 for that rusty lock, improving how well insulin worked by 35% compared to just 5% with placebo. The teens on semaglutide also saw their liver enzymes (a sign of liver stress) drop by 18% versus 3% with placebo, like their liver was finally getting a break from processing excess sugar. Most impressively, those who lost 20% or more of their BMI saw even greater improvements across the board - as if crossing that threshold unlocked additional metabolic benefits.

Statistics Decoded

The p-values ranged from 0.0001 to 0.0232, meaning these results were extremely unlikely due to chance - like flipping heads 1,000 times in a row for the strongest effects. The 16.7 percentage point BMI difference means if placebo lost 2%, semaglutide lost nearly 19%. HOMA-IR dropping 35% vs 5% means insulin resistance improved dramatically - imagine your car going from 10 mpg to 15 mpg efficiency. The 33.6% vs 10.1% fasting insulin reduction shows the pancreas didn't have to work as hard. All cholesterol measures improved significantly, with p-values under 0.05 meaning these weren't flukes.

Why This Matters

This is the first major study showing that semaglutide doesn't just help obese teens lose weight - it fundamentally improves their metabolic health in ways that could prevent type 2 diabetes and heart disease for decades. For doctors, it provides concrete evidence that early intervention with GLP-1 drugs could reshape the trajectory of obesity-related health problems in young people.

Original Abstract

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. 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. 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%. 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.