PMID-36322838 — STEP TEENS: Once-Weekly Semaglutide in Adolescent Obesity (Phase 3)

[DRAFT — authored 2026-04-19. Citation web-verified 2026-04-19 against PubMed.]

Citation

Weghuber D, Barrett T, Barrientos-Pérez M, Gies I, Hesse D, Jeppesen OK, Kelly AS, Mastrandrea LD, Sørrig R, Arslanian S, on behalf of the STEP TEENS Investigators. Once-Weekly Semaglutide in Adolescents with Obesity. N Engl J Med. 2022;387(24):2245-2257. doi: 10.1056/NEJMoa2208601. PMID: 36322838. ClinicalTrials.gov NCT04102189.

External URL: DOI resolver

Study Design

Phase: 3
Design: Multicenter, randomized, double-blind, placebo-controlled
Randomization: 2:1 to semaglutide 2.4 mg weekly SC or matching placebo
Duration: 68 weeks treatment + 7-week follow-up
N: 201 participants (ages 12 to <18 years)
Setting: Multinational

Population

Adolescents aged 12 to <18 years
Obesity (BMI ≥95th percentile for age and sex) or overweight (BMI ≥85th percentile) with at least one weight-related comorbidity
Mean baseline BMI approximately 37 kg/m²
Concurrent lifestyle intervention (reduced-calorie diet and increased physical activity)

Intervention

Semaglutide: 0.25 mg weekly → titrated to 2.4 mg weekly over 17 weeks (standard Wegovy titration)
Placebo: Matching weekly SC injection with identical titration schedule
Both arms: supervised lifestyle intervention

Outcomes

Primary — Percent change in BMI at week 68

Semaglutide 2.4 mg: -16.1% mean BMI reduction
Placebo: +0.6% mean BMI change — slight increase (growth-adjusted)
Between-group difference: Approximately -16.7 percentage points (P<0.001)

Key Secondary

Body weight change: Corresponding large reductions in the semaglutide arm
Proportion achieving ≥5% body weight reduction: ~73% semaglutide vs ~18% placebo
Cardiometabolic improvements: Waist circumference, HbA1c, lipids, ALT all improved in semaglutide arm
Quality of life: Improvements in physical functioning and related PROs

Safety

GI adverse events (nausea, vomiting, diarrhea, abdominal pain) predominant in semaglutide arm — similar in character to adult STEP data
Cholelithiasis events reported in semaglutide arm; gallbladder-event monitoring appropriate
No new pediatric-specific safety signals
Serious adverse events numerically similar between arms

Key Findings

STEP TEENS is the landmark Phase 3 trial establishing semaglutide's efficacy and safety in adolescent obesity. The -16.1% mean BMI reduction is substantially larger than any prior pediatric anti-obesity pharmacotherapy trial. Core points:

Adolescents respond comparably to adults. Effect size (percent BMI/body-weight reduction) approaches adult STEP 1 outcomes.
Developmental context. Placebo arm shows slight BMI increase consistent with ongoing puberty-related adiposity trajectory, underscoring that "BMI stability" in this age group is not clinically inert.
FDA approval followed. Semaglutide (Wegovy) received FDA expanded approval for use in adolescents aged ≥12 years with obesity based on STEP TEENS data.
Clinical integration: Obesity-specialty pediatric care, structured lifestyle intervention, and family-centered counseling remain essential alongside pharmacotherapy.

Clinical Relevance

Youth-onset obesity is a strong predictor of adult obesity and its complications. STEP TEENS supports:

Semaglutide 2.4 mg weekly as an evidence-based option for adolescents ≥12 years with obesity (BMI ≥95th percentile) or overweight (≥85th percentile) with weight-related comorbidity
Use within a structured lifestyle-intervention framework
Pediatric obesity medicine specialist oversight where available

Companion pediatric evidence:

Tirzepatide in adolescents with T2D (not obesity indication): PMID-40975112 – SURPASS-PEDS Tirzepatide Youth — SURPASS-PEDS (Hannon 2025).
ADA Standards of Care 2025/2026 Section 14 covers pediatric pharmacotherapy alignment.

Limitations (Author-acknowledged)

Adolescent population; continued surveillance of long-term developmental, reproductive, and psychosocial outcomes is ongoing
68-week duration; sustained maintenance of effect and weight regain on discontinuation require longer follow-up
Generalizability across adolescent-obesity phenotypes requires care
Underrepresentation of certain pediatric subpopulations (younger children <12, severe syndromic obesity)

Evidence Level

Level Ib (Oxford CEBM) — adequately-powered Phase 3 RCT with pre-specified primary endpoint.

Linked Peptides

Semaglutide

Related Studies

PMID-40975112 – SURPASS-PEDS Tirzepatide Youth (tirzepatide in youth T2D — companion pediatric evidence)
PMID-33567185 – Once-Weekly Semaglutide in Adults with Overweight or Obesity (adult STEP 1 benchmark)

Orchestrator Notes

Citation web-verified 2026-04-19 via PubMed.
NCT04102189 confirmed.
Primary evidence for Semaglutide profile pediatric-prescribing section.

PMID-36322838 – STEP TEENS Semaglutide Adolescents