Liraglutide for Children 6 to <12 Years of Age with Obesity — A Randomized Trial

In children 6 to <12 years with obesity, daily liraglutide plus lifestyle counseling reduced BMI versus placebo, with gastrointestinal side effects; NNT ≈ 3 for ≥5% BMI reduction.

Background

Childhood obesity is a chronic, relapsing disease with significant long-term cardiometabolic risks. While GLP-1 agonists (e.g., liraglutide) are approved for adolescents ≥12 years, no medications are approved for children <12 years with nonmonogenic, nonsyndromic obesity. This trial evaluated the efficacy and safety of liraglutide in children 6 to <12 years old as an adjunct to lifestyle intervention.

Patients

• Population: 82 children aged 6 to <12 years with obesity (BMI ≥95th percentile per CDC), Tanner stage 1–5; nonmonogenic, nonsyndromic; no type 1 diabetes or secondary causes of obesity.
• Baseline: Mean age 10 years; 54% male; 72% White; obesity class 2 (37%) or class 3 (39%); mean BMI ~31 kg/m²; mean weight ~70 kg.
• Sites: 23 centers across 9 countries.

Intervention

• Liraglutide subcutaneous once daily, titrated to 3.0 mg (or maximum tolerated dose), plus standardized lifestyle counseling (healthy diet; goal ≥60 minutes/day moderate-to-vigorous activity; optional activity tracker).

Control

• Placebo subcutaneous once daily, plus identical lifestyle counseling.

Outcome

• Primary: Percentage change in BMI from baseline to week 56.
• Confirmatory secondary:
  • Percentage change in body weight to week 56.
  • Proportion with ≥5% BMI reduction at week 56.
• Supportive secondary (selected): ≥10% BMI reduction; change in BMI as % of 95th percentile; BMI standard-deviation score (SDS); absolute weight (kg); waist circumference; blood pressure; glycated hemoglobin (HbA1c).
• Safety: Adverse events (AEs), serious AEs, discontinuations due to AEs; growth and pubertal development.

Study Design

• Phase 3a, multicenter, randomized (2:1), double-blind, placebo-controlled trial.
• Run-in: 12 weeks with lifestyle counseling; Treatment: 56 weeks; Post-treatment follow-up: 26 weeks (to week 82).
• Randomization stratified by sex and Tanner stage; analyses used treatment-policy estimand.

Level of Evidence

Level 1b (individual randomized controlled trial).

Follow up period

• Treatment: 56 weeks.
• Post-treatment follow-up: 26 weeks (weeks 56–82).

Results

Primary outcome

• % change in BMI at week 56: Liraglutide −5.8% vs placebo +1.6%; estimated difference −7.4 percentage points (95% CI, −11.6 to −3.2).

Confirmatory secondary outcomes

• % change in body weight: Liraglutide +1.6% vs placebo +10.0%; estimated difference −8.4 percentage points (95% CI, −13.4 to −3.3).
• ≥5% BMI reduction: 46% vs 9%; adjusted OR 6.3 (95% CI, 1.4 to 28.8). NNT = 3 (absolute risk difference 37%).

Supportive secondary outcomes

• Absolute weight change: +1.1 kg vs +7.1 kg; difference −6.0 kg (95% CI, −9.3 to −2.7).
• ≥10% BMI reduction: 35% vs 4%; NNT = 4 (absolute risk difference 31%).
• BMI % of 95th percentile: −14.0 vs −4.0 percentage points; difference −10.0 (95% CI, −15.1 to −4.8).
• BMI SDS: −0.7 vs −0.3; difference −0.4 (95% CI, −0.6 to −0.2).
• Waist circumference: −2.0 cm vs +1.3 cm; difference −3.4 cm (95% CI, −9.4 to 2.7).
• Blood pressure (mm Hg): Systolic difference −3.4 (95% CI, −8.9 to 2.0); Diastolic difference −4.2 (95% CI, −8.4 to 0.0).
• HbA1c: −0.2% vs −0.1%; difference −0.1% (95% CI, −0.2 to 0.0).

Post-treatment follow-up (weeks 56–82)

• Both BMI and body weight increased after discontinuation in both groups, consistent with chronicity of obesity; liraglutide group retained lower BMI % of 95th percentile and BMI SDS than placebo at week 82.

Safety

• Any AE: 89% (liraglutide) vs 88% (placebo).
• Gastrointestinal AEs: 80% vs 54% (mostly mild–moderate nausea/vomiting during dose escalation; managed with antiemetics, dose reduction, or temporary interruption).
• Serious AEs: 12% vs 8%; three GI events in liraglutide group deemed possibly/probably related; resolved without sequelae; no deaths.
• Discontinuation due to AEs: 11% vs 0%.
• Growth/puberty: No apparent adverse effects on height, bone age, or Tanner stage over 56 weeks; pulse similar between groups; amylase/lipase increases remained within normal ranges.

Limitations

• Modest sample size; majority White (~70%), limiting generalizability.
• No standardized international threshold for clinically meaningful BMI reduction in children.
• Obesity-related complications self-reported to investigators; potential under-ascertainment.
• No formal screening/monitoring for eating disorders; bone mineral density not assessed.
• Post-treatment rebound underscores need for longer-term data; open-label extension ongoing.

Funding

Supported by Novo Nordisk.

Citation

Fox CK, Barrientos‑Pérez M, Bomberg EM, et al.; SCALE Kids Trial Group. Liraglutide for Children 6 to <12 Years of Age with Obesity — A Randomized Trial. New England Journal of Medicine. 2025;392:555-565. doi:10.1056/NEJMoa2407379.