STEP TEENS: Semaglutide for Adolescent Obesity — 16% BMI Reduction

Medically reviewed by Dr. James Whitfield, DO, FACOI

Childhood obesity is a growing epidemic with limited treatment options. The STEP TEENS trial, published in the NEJM in 2022, showed that semaglutide 2.4mg reduced BMI by 16.1% in adolescents aged 12-17 — with over 40% of participants dropping below the obesity threshold entirely.

STEP TEENS: Addressing the Adolescent Obesity Crisis

Childhood and adolescent obesity has reached epidemic proportions globally, with limited pharmacological treatment options available for young patients. The STEP TEENS trial, published in the New England Journal of Medicine in November 2022 by Weghuber et al., provided the first rigorous evidence that semaglutide 2.4 mg is safe and effective for weight management in adolescents aged 12-17 years [1].

The Scale of Adolescent Obesity

Before examining the trial data, it is important to understand the clinical context:

Approximately 20% of adolescents in the United States have obesity

Adolescent obesity is associated with type 2 diabetes, hypertension, dyslipidemia, NAFLD, sleep apnea, and psychological distress

Without intervention, 80% of adolescents with obesity will carry it into adulthood

Prior to semaglutide, the only FDA-approved pharmacotherapy for adolescents was orlistat, which has modest efficacy and significant gastrointestinal side effects

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Study Design

STEP TEENS was a 68-week, randomized, double-blind, placebo-controlled trial:

Enrollment: 201 adolescents aged 12-17 years

Population: BMI at or above the 95th percentile for age and sex (obesity), or at or above the 85th percentile with at least one weight-related comorbidity

Intervention: Semaglutide 2.4 mg or placebo, once-weekly subcutaneous injection

Lifestyle intervention: All participants received counseling on nutrition, physical activity, and behavioral strategies

Primary endpoint: Percentage change in BMI from baseline to week 68

BMI and Weight Results

The results in adolescents were striking — and in some measures exceeded the adult STEP 1 results:

BMI Change (Primary Endpoint):

Semaglutide: -16.1% BMI reduction

Placebo: +0.6% BMI increase

Treatment difference: -16.7 percentage points (95% CI, -20.3 to -13.2; P<0.001)

Body Weight Change:

Semaglutide: -14.7% body weight reduction

Placebo: +2.8% weight gain

Treatment difference: -17.4 percentage points

Categorical BMI Reduction:

≥5% BMI reduction: 72.5% semaglutide vs. 17.7% placebo

≥10% BMI reduction: 61.8% vs. 8.1%

≥15% BMI reduction: 53.4% vs. 4.8%

≥20% BMI reduction: 36.4% vs. 0% [1]

Crossing the Obesity Threshold

A post-hoc analysis by Kelly et al. (2023) examined how many adolescents moved to lower BMI categories during treatment:

>40% of semaglutide-treated adolescents dropped below the obesity threshold (95th percentile)

Many moved from obesity to overweight, and some reached normal weight

In contrast, very few placebo-treated adolescents changed BMI category

This represents a clinically meaningful outcome — moving below the obesity threshold is associated with reduced long-term cardiometabolic risk [2].

Cardiometabolic Improvements

Beyond BMI reduction, STEP TEENS demonstrated important metabolic benefits:

Waist circumference: -7.3% semaglutide vs. +2.0% placebo

HbA1c: Improved in semaglutide group

Fasting insulin: Significantly reduced, indicating improved insulin sensitivity

ALT (liver enzyme): 18.3% reduction with semaglutide, suggesting hepatoprotective effects

Lipid profile: Improvements in triglycerides and cholesterol

Blood pressure: Trends toward improvement

The ALT reduction was particularly notable, as many adolescents with obesity have undiagnosed NAFLD. Bensignor et al. (2024) published a detailed analysis of the metabolic improvements, demonstrating significant improvements in insulin sensitivity markers [3].

Safety in Adolescents

Safety in a pediatric population requires particularly careful evaluation:

Adverse Events:

Gastrointestinal events were the most common (nausea, vomiting, diarrhea), consistent with the adult profile

Most were mild to moderate and occurred during dose escalation

Serious adverse events: 11.0% semaglutide vs. 9.0% placebo

Growth and Development:

No adverse effects on linear growth (height) were observed during the 68-week trial

Bone density was not adversely affected

Puberty progression was not impacted

Discontinuation:

5.5% of semaglutide patients discontinued due to adverse events vs. 4.5% placebo

The safety profile was generally consistent with the adult experience, though the authors noted that longer-term safety monitoring in growing adolescents is warranted [1].

Psychological and Quality-of-Life Outcomes

STEP TEENS also assessed patient-reported outcomes:

Impact of Weight on Quality of Life (IWQOL-Kids): Significantly improved with semaglutide

Physical functioning: Improved

Body esteem: Trends toward improvement

These findings are particularly important given the psychological burden of obesity in adolescence, including bullying, social isolation, and depression

Regulatory and Clinical Impact

STEP TEENS led to significant regulatory and clinical developments:

FDA approval: In December 2022, the FDA approved Wegovy for adolescents aged 12 and older with obesity — making semaglutide the first GLP-1 receptor agonist approved for pediatric weight management.

Guideline updates: The American Academy of Pediatrics (AAP) updated its clinical practice guidelines in 2023 to include GLP-1 receptor agonists as treatment options for adolescents with obesity.

Treatment access: The approval opened a new treatment pathway for adolescents who had previously been limited to lifestyle intervention alone or, in severe cases, bariatric surgery.

Limitations and Open Questions

Several important questions remain:

Long-term effects: The 68-week trial does not address effects beyond approximately 16 months, including impacts on growth, bone health, and development during puberty

Weight regain after discontinuation: Not studied in the adolescent population

Younger children: STEP TEENS enrolled ages 12-17; data in younger children is lacking

Eating disorders: Careful screening is needed, as weight-focused interventions in adolescents require sensitivity to eating disorder risk [1]

> Related Comparison: Ozempic vs Mounjaro: Complete Comparison

References

Weghuber D, Barrett T, Barrientos-Pérez M, et al. "Once-Weekly Semaglutide in Adolescents with Obesity." New England Journal of Medicine. 2022;387(24):2245-2257. PubMed: 36322838

Kelly AS, Bensignor MO, Hsia DS, et al. "Reducing BMI below the obesity threshold in adolescents treated with once-weekly subcutaneous semaglutide 2.4 mg." Obesity. 2023;31(8):2139-2149. PubMed: 37196421

Bensignor MO, et al. "Semaglutide for Management of Obesity in Adolescents." Pediatric Obesity. 2024. PMC: 11222026

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