Effect of Semaglutide on Insulin Sensitivity and Cardiometabolic Risk Factors in Adolescents With Obesity: The STEP TEENS Study.
Arslanian. Silva S; Gies. Inge I; Goldman. Bryan B; Karlsson. Tobias T; Kelly. Aaron S AS; Skalshøi Kjær. Mette M; Körner. Antje A; Noureddin. Mazen M; Wabitsch. Martin M; Harder-Lauridsen. Nina M NM; Weghuber. Daniel D
Key Findings
- Semaglutide 2.4 mg weekly reduced BMI by 16.7 percentage points vs. placebo in adolescents.
- Fasting insulin fell 33.6% and HOMA‑IR (insulin resistance) fell 35% with semaglutide, far more than placebo.
- Glycated hemoglobin, fasting glucose, ALT, waist‑to‑height ratio, triglycerides, LDL and total cholesterol all improved significantly.
Practical Outcomes
- For biohackers interested in weight loss and metabolic health, a 2.4 mg weekly dose of semaglutide appears to be a powerful protocol that can dramatically cut weight and improve insulin sensitivity and lipid profiles. The benefits scale with the amount of weight lost, so aiming for ≥20% reduction may maximize metabolic gains. Because semaglutide is a prescription drug with potential side effects, it should be used under medical supervision, with regular monitoring of blood glucose, liver enzymes, and lipid panels.
Summary
In a study of teens with obesity, a once‑weekly injection of semaglutide (2.4 mg) cut body‑mass index by about 17% after 68 weeks and also made the body more insulin‑sensitive, lowered blood sugar, reduced liver enzymes, and improved cholesterol and triglycerides. Bigger weight loss (≥20%) gave even stronger metabolic benefits.
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.
Study Information
pubmed
2025
2025-11-26T00:00:00.000Z
10.2337/dc25-0824