Evidence for Semaglutide Use in Children with Obesity
Semaglutide is effective for weight management in adolescents with obesity (ages 12-17), with clinical trial evidence showing a 16.1% reduction in BMI compared to 0.6% with placebo over 68 weeks, and should be considered as part of a comprehensive weight management approach for adolescents with obesity. 1
Efficacy in Adolescents
The strongest evidence for semaglutide use in adolescents comes from a double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine:
- Mean BMI reduction of 16.1% with semaglutide vs. 0.6% with placebo at 68 weeks 1
- 73% of adolescents achieved ≥5% weight loss with semaglutide vs. 18% with placebo 1
- Significant improvements in cardiometabolic risk factors including:
- Reduced waist circumference
- Improved glycated hemoglobin levels
- Improved lipid profiles (except HDL cholesterol)
- Reduced alanine aminotransferase levels 1
A recent observational study (2024) supports these findings, showing that after 6 months of treatment:
- BMI SDS decreased by 0.32±0.27 (p<0.001)
- Mean weight loss of 7.03±7.50 kg (p<0.001)
- Mean percentage total weight loss of 6.4±6.3% 2
At 12 months, available data showed:
- BMI SDS decreased by 0.54±0.52 (p<0.001)
- Mean weight loss of 9.7±10.8 kg (p<0.001)
- Mean percentage total weight loss of 8.9±10.0% 2
Dosing and Administration
Based on clinical trial evidence, the recommended dosing protocol for adolescents is similar to adults:
- Starting dose: 0.25 mg once weekly
- Gradual titration over 8 weeks to a final dose of 1-2.4 mg weekly 2, 1
This gradual titration helps minimize gastrointestinal side effects and optimize tolerability.
Safety Profile and Adverse Effects
Common adverse effects include:
- Gastrointestinal events (62% with semaglutide vs. 42% with placebo) 1
- Nausea
- Vomiting
- Diarrhea
- Constipation
More serious but less common adverse effects:
- Cholelithiasis (4% in semaglutide group vs. 0% in placebo) 1
- Serious adverse events reported in 11% of semaglutide group vs. 9% of placebo group 1
Patient Selection
Semaglutide should be considered for:
- Adolescents aged 12-17 years with obesity (BMI ≥95th percentile for age and sex) 1
- Adolescents with overweight (BMI ≥85th percentile) plus at least one weight-related comorbidity 1
- Patients with comorbid conditions such as:
- Insulin resistance
- Type 2 diabetes
- Metabolic-associated fatty liver disease
- Obstructive sleep apnea
- Hypertension 2
Special Considerations
Genetic Forms of Obesity
Case reports suggest semaglutide may be effective in monogenic forms of obesity:
- A 13-year-old boy with MC4R mutation achieved 11% weight loss at 12 months with semaglutide
- Improved quality of life scores from 35.95 to 60.36 at 12-month review
- Improved glycemic control as measured by continuous glucose monitoring 3
Long-term Considerations
- Limited long-term safety data in adolescents, particularly regarding risks of:
- Cholelithiasis
- Pancreatitis
- Suicidal ideation
- Disordered eating 4
- Cost-effectiveness analyses have shown unfavorable incremental cost-effectiveness ratios compared to other anti-obesity medications like phentermine-topiramate 4
Implementation in Clinical Practice
For optimal outcomes:
- Use semaglutide as part of a multidisciplinary approach including dietary and lifestyle interventions 2
- Monitor for gastrointestinal side effects, which are common but typically mild 2
- Screen for and monitor gallbladder disease due to increased risk of cholelithiasis 1
- Consider long-term maintenance therapy, as weight regain is likely with discontinuation
Limitations and Future Directions
Current limitations in the evidence base include:
- Limited long-term safety and efficacy data beyond 68 weeks in adolescents 4
- Need for more research on utilization patterns and adherence 4
- Potential for worsening socioeconomic disparities in pediatric obesity management due to cost 4
Future research should focus on long-term outcomes, optimal duration of therapy, and strategies to improve access and affordability.