What are the guidelines for using Liraglutide (Glucagon-like peptide-1 receptor agonist) in children with obesity?

Liraglutide Use in Children with Obesity

Liraglutide 3.0 mg is approved and recommended for adolescents aged 12 years and older with obesity as an adjunct to lifestyle modification, but should only be used after lifestyle interventions have failed or in the presence of severe complications. 1

Age-Specific Indications and Approval Status

Adolescents (12 to <18 years)

• Liraglutide 3.0 mg is approved for use in adolescents ≥12 years with obesity in several countries 1
• The FDA label for liraglutide (for diabetes) establishes safety in pediatric patients ≥10 years, though the 3.0 mg obesity indication specifically targets adolescents 12-17 years 2
• A phase 3 trial in 251 adolescents (12 to <18 years) demonstrated significant BMI standard-deviation score reduction of -0.22 compared to placebo (P = 0.002) over 56 weeks 1, 3

Younger Children (6 to <12 years)

• Recent evidence from 2025 supports liraglutide use in children aged 6 to <12 years with obesity 4
• A randomized trial of 82 children (6 to <12 years) showed mean BMI reduction of -5.8% with liraglutide versus +1.6% with placebo (estimated difference -7.4 percentage points, P<0.001) at 56 weeks 4
• 46% of children achieved ≥5% BMI reduction versus 9% with placebo 4
• Short-term safety data in children aged 7-11 years showed a tolerability profile similar to adults and adolescents 5

Clinical Criteria for Initiating Therapy

Pharmacotherapy should only be considered when:

• Lifestyle modification (diet and exercise) has been ineffective 1
• OR the patient has severe obesity-related complications 1
• Pharmacotherapy must always be used as an adjunct to behavioral change, never as monotherapy 1

Dosing Protocol

Titration Schedule

• Start at 0.6 mg subcutaneously once daily for 7 days 1, 2
• Increase by 0.6 mg weekly: 1.2 mg (week 2) → 1.8 mg (week 3) → 2.4 mg (week 4) → 3.0 mg (week 5) 1
• The gradual titration minimizes gastrointestinal adverse effects 1
• Slower titration may be used based on individual tolerance 1

Maximum Dose

• 3.0 mg subcutaneously once daily is the target maintenance dose for obesity 1, 4
• For diabetes management in children ≥10 years, maximum dose is 1.8 mg daily 2

Efficacy Monitoring and Discontinuation Criteria

Evaluate treatment response at specific timepoints:

• Discontinue liraglutide if <4% body weight loss after 16 weeks of treatment 1
• Alternative threshold: Discontinue if BMI or BMI z-score reduction is <4% after 12 weeks at maximum dose 1
• In adolescents, 43.3% achieved ≥5% BMI reduction and 26.1% achieved ≥10% BMI reduction 3
• In younger children (6 to <12 years), 46% achieved ≥5% BMI reduction 4

Safety Profile and Adverse Effects

Common Adverse Events

• Gastrointestinal adverse events are the most common, occurring in 64-80% of pediatric patients 1, 4, 3
• Nausea and vomiting are particularly frequent (40% and 16% respectively in adults; similar rates in children) 1
• In children 6 to <12 years, 80% experienced GI adverse events versus 54% with placebo 4
• In adolescents, 64.8% had GI adverse events versus 36.5% with placebo 3

Serious Adverse Events

• Serious adverse events occurred in 2.4-12% of liraglutide-treated pediatric patients versus 4-8% with placebo 4, 3
• Acute kidney injury and hepatic injury have been reported in adolescents, even at low doses (0.6 mg/day) 6
• Hypoglycemia risk is higher in pediatric patients regardless of concomitant insulin or metformin use 2
• Rare cases of acute pancreatitis (<0.1%) and symptomatic gallstones (<0.05%) reported in adults 1

Discontinuation Rates

• Adverse events leading to discontinuation occurred in 10.4% of adolescents on liraglutide versus 0% on placebo 3
• Most adverse events are mild to moderate in severity 1, 4, 5

Critical Monitoring Requirements

Close pediatric monitoring is mandatory to identify adverse effects: 1

• Monitor for gastrointestinal symptoms at each visit, especially during titration 1
• Assess weight/BMI at each follow-up visit 1
• Monitor renal function and hepatic transaminases, particularly given case reports of acute kidney injury and liver injury in adolescents 6
• Monitor for hypoglycemia, especially in patients on insulin or metformin 2
• Evaluate mood and mental health status given one reported suicide in adolescent trials (though assessed as unlikely related to treatment) 3

Important Clinical Considerations

Contraindications and Precautions

• Liraglutide should not be used with other GLP-1 receptor agonists or DPP-4 inhibitors 1
• Use caution in patients with renal impairment; dehydration may worsen renal function 2
• Limited data in hepatic impairment; use with caution 2
• Not studied in patients with pre-existing gastroparesis 2

Missed Doses

• If a dose is missed, resume the regular schedule with the next dose; do not double up 2
• If >3 days have elapsed since last dose, reinitiate at 0.6 mg daily and retitrate to minimize GI symptoms 2

Duration of Effect

• Weight regain occurs after discontinuation: BMI standard-deviation score increased by 0.15 more in the liraglutide group versus placebo during 26-week follow-up after stopping treatment 3
• This suggests liraglutide may need to be continued long-term for sustained benefit 3

Comparison to Other Pediatric Obesity Medications

• Orlistat is also approved for adolescents >12 years but produces more modest BMI reduction (0.55-0.8 kg/m²) 1
• Orlistat has high rates of GI adverse events and treatment discontinuation in population studies 1
• Metformin (approved for T2DM in children ≥10 years) can cause weight loss but lacks long-term efficacy data for obesity without diabetes 1
• Liraglutide appears to perform favorably compared to other approved pharmacological agents for pediatric obesity 7

Evidence Quality and Limitations

• The 2023 consensus guidelines from Obesity Reviews provide the most recent and comprehensive guidance on pediatric obesity pharmacotherapy 1
• High-quality phase 3 RCT data exist for adolescents 12 to <18 years 3
• Emerging 2025 data now support use in younger children (6 to <12 years), representing the newest evidence 4
• Long-term safety data beyond 56 weeks remain limited in pediatric populations 1
• The risk-benefit ratio remains uncertain due to lack of long-term studies 1

Common Pitfalls to Avoid

• Do not use liraglutide as first-line therapy; lifestyle modification must be attempted first 1
• Do not continue therapy beyond 12-16 weeks if inadequate weight loss response (<4%) 1
• Do not skip the gradual titration schedule, as this increases GI adverse effects 1
• Do not overlook monitoring for renal and hepatic complications, even at low doses 6
• Do not assume benefits will persist after discontinuation; plan for long-term therapy 3