Completed Pediatric Trials Overview
Two GLP-1 receptor agonists have completed pivotal adolescent trials leading to FDA approval: semaglutide (Wegovy) and liraglutide (Saxenda). Here's the data that regulators reviewed.
STEP TEENS: Detailed Results
| Outcome | Semaglutide (n=134) | Placebo (n=67) | Difference |
|---|---|---|---|
| BMI change (%) | -16.1% | +0.6% | -16.7 pp (p<0.001) |
| Weight change (kg) | -15.3 kg | +2.4 kg | -17.7 kg |
| ≥5% weight loss | 73.4% | 17.9% | — |
| ≥10% weight loss | 62.3% | 10.4% | — |
| ≥15% weight loss | 53.4% | 4.5% | — |
| ≥20% weight loss | 36.4% | 1.5% | — |
Notable: Adolescent efficacy exceeded adult trials. In STEP 1 (adults), 14.9% achieved ≥20% weight loss compared to 36.4% in STEP TEENS. Adolescents appear more responsive to semaglutide.
STEP TEENS: Safety Data
| Adverse Event | Semaglutide | Placebo |
|---|---|---|
| Any adverse event | 91.7% | 89.5% |
| Nausea | 41.7% | 11.9% |
| Vomiting | 36.4% | 9.0% |
| Diarrhea | 21.2% | 11.9% |
| Abdominal pain | 15.2% | 9.0% |
| Gallbladder-related events | 3.8% | 0% |
| Serious adverse events | 10.6% | 7.5% |
| Discontinuation due to AE | 5.2% | 4.4% |
Secondary Outcomes: Metabolic Improvements
| Cardiometabolic Marker | Semaglutide Change | Placebo Change |
|---|---|---|
| Waist circumference | -12.2 cm | +0.4 cm |
| Systolic blood pressure | -3.0 mmHg | +2.0 mmHg |
| Triglycerides | -23% | +9% |
| LDL cholesterol | -7% | +4% |
| HbA1c | -0.20 pp | +0.03 pp |
| Fasting glucose | -4.4 mg/dL | +1.4 mg/dL |
Liraglutide Adolescent Trial: Key Results
This was the first GLP-1 trial in adolescents to lead to FDA approval. The primary endpoint was change in BMI standard deviation score (SDS)—a measure that adjusts for age and sex.
| Outcome | Liraglutide (n=125) | Placebo (n=126) |
|---|---|---|
| BMI SDS change | -0.22 | +0.14 |
| BMI % change | -4.64% | +1.55% |
| ≥5% BMI reduction | 43.3% | 18.7% |
| ≥10% BMI reduction | 26.1% | 8.1% |
Comparison note: Semaglutide significantly outperformed liraglutide in adolescents (16.1% vs 4.64% BMI reduction). This mirrors the adult literature where semaglutide consistently shows greater efficacy. Liraglutide also requires daily injections versus semaglutide's weekly.
Ongoing Pediatric Trials
SURMOUNT-PEDS is the key trial that could lead to tirzepatide (Zepbound) approval in adolescents. Given tirzepatide's superior weight loss in adults (20-25% vs 15-17% for semaglutide), expectations are high.
STEP YOUNG is particularly significant—it's studying semaglutide in children aged 6-11, potentially opening GLP-1 therapy to elementary school-aged patients if successful.
Head-to-Head Comparison: Pediatric Trials
| Parameter | STEP TEENS (Semaglutide) | Liraglutide Trial |
|---|---|---|
| BMI reduction | -16.1% | -4.64% |
| Dosing | Weekly injection | Daily injection |
| ≥5% BMI loss achieved | 73.4% | 43.3% |
| ≥10% BMI loss achieved | 62.3% | 26.1% |
| GI side effects | Common (nausea 42%, vomiting 36%) | Common (nausea 39%, vomiting 23%) |
| Discontinuation rate | 5.2% | 6.5% |
What The Data Tells Us
- Adolescents respond well: Weight loss efficacy in teens equals or exceeds adult results
- Semaglutide outperforms liraglutide: 3-4x greater BMI reduction with weekly vs daily dosing
- GI side effects are common but manageable: Nausea and vomiting occur frequently but rarely lead to discontinuation
- Gallbladder risk is real: Rapid weight loss increases cholelithiasis risk regardless of mechanism
- No growth concerns detected: Linear height growth continued normally during treatment
- Metabolic improvements mirror weight loss: Blood pressure, lipids, and glucose parameters improved
Evidence Gaps: What We Still Need
Despite encouraging results, significant questions remain unanswered by current pediatric data:
| Question | Current Status | When We'll Know More |
|---|---|---|
| Long-term efficacy/safety | Maximum 68 weeks data | Extension studies ongoing |
| Effects on pubertal development | No signal of harm in 68 weeks | Long-term registry data needed |
| Bone health long-term | Not specifically studied | Future trials should include DEXA |
| What happens after stopping | Adult data shows regain; pediatric unknown | Discontinuation studies needed |
| Optimal treatment duration | Unknown | No guidance available |
| Children under 12 | Not FDA-approved; STEP YOUNG ongoing | 2026+ for results |
How to Interpret Trial Results
When evaluating pediatric GLP-1 data, keep these methodological points in mind:
BMI vs. BMI SDS vs. Weight
Different trials use different primary endpoints. BMI SDS (standard deviation score) adjusts for age and sex—useful for growing children whose "normal" BMI changes with age. Percentage BMI change is more intuitive. Absolute weight change is misleading in adolescents who are still growing.
Lifestyle Intervention in Both Arms
All trials included lifestyle counseling for both active drug and placebo groups. The placebo group shows what lifestyle intervention alone achieves (typically minimal effect). The treatment difference represents the added benefit of medication.
Completer vs. ITT Analysis
Intention-to-treat (ITT) analysis includes all randomized patients regardless of completion. This is more conservative but reflects real-world effectiveness. "Completer" analyses only include those who finished the trial—showing best-case scenarios.
- Weghuber D, et al. Once-Weekly Semaglutide in Adolescents with Obesity. N Engl J Med. 2022;387:2245-2257. (STEP TEENS)
- Kelly AS, et al. A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity. N Engl J Med. 2020;382:2117-2128.
- ClinicalTrials.gov. NCT04102189 (STEP TEENS).
- ClinicalTrials.gov. NCT02918279 (Liraglutide Adolescent Trial).
- ClinicalTrials.gov. NCT05260021 (SURMOUNT-PEDS).
- ClinicalTrials.gov. NCT05726253 (STEP YOUNG).
- FDA. Wegovy Approval for Pediatric Obesity. Press Release, December 2022.
- FDA. Saxenda Approval for Pediatric Obesity. Press Release, December 2020.
- Hampl SE, et al. Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents with Obesity. Pediatrics. 2023.
- Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021. (STEP 1 for comparison)
- FDA. Wegovy Prescribing Information. 2021, updated 2024.
- FDA. Saxenda Prescribing Information. 2020, updated 2024.