RCT: Liraglutide for Children Aged 6 to <12 Years with Obesity
14 Sep, 2024 | 19:40h | UTCSummary:
A recent phase 3a randomized, double-blind, placebo-controlled trial published in the New England Journal of Medicine examined the efficacy and safety of liraglutide in children aged 6 to less than 12 years with obesity. Currently, no medications are approved for treating nonmonogenic, nonsyndromic obesity in this age group, making this study particularly noteworthy.
Methods:
- Participants: 82 children with obesity (BMI ≥95th percentile for age and sex).
- Design: Participants were randomized in a 2:1 ratio to receive once-daily subcutaneous liraglutide (up to 3.0 mg) or placebo, alongside lifestyle interventions, over a 56-week treatment period, followed by a 26-week follow-up.
- Primary Endpoint: Percentage change in BMI from baseline to week 56.
- Secondary Endpoints: Percentage change in body weight and the proportion achieving a ≥5% reduction in BMI.
Results:
- BMI Reduction: At week 56, the liraglutide group experienced a mean BMI reduction of –5.8%, compared to a +1.6% increase in the placebo group. The estimated difference was –7.4 percentage points (95% CI, –11.6 to –3.2; P<0.001).
- Body Weight: Mean body weight increased by 1.6% in the liraglutide group versus 10.0% in the placebo group, a difference of –8.4 percentage points (95% CI, –13.4 to –3.3; P=0.001).
- BMI Reduction ≥5%: Achieved by 46% of participants in the liraglutide group versus 9% in the placebo group (adjusted odds ratio, 6.3; 95% CI, 1.4 to 28.8; P=0.02).
- Adverse Events: Reported in 89% of the liraglutide group and 88% of the placebo group. Gastrointestinal events were more common with liraglutide (80% vs. 54%).
Discussion:
While the study suggests that liraglutide can lead to a statistically significant reduction in BMI among children aged 6 to less than 12 years with obesity, several considerations should temper our enthusiasm:
- Sample Size and Diversity: The trial included only 82 participants, with a predominantly White population (72%), which may limit the generalizability of the findings to broader, more diverse populations.
- Duration and Long-Term Effects: The study spanned 56 weeks, with a 26-week follow-up. The long-term efficacy and safety of liraglutide in this age group remain uncertain, particularly concerning growth, development, and potential rebound weight gain after discontinuation.
- Clinical Significance: Although the reduction in BMI was statistically significant, the clinical significance—especially regarding long-term health outcomes and obesity-related comorbidities—is less clear. Obesity is a chronic and relapsing condition, and a modest reduction in BMI may not translate into substantial health benefits without sustained intervention.
- Adverse Events: The high incidence of gastrointestinal adverse events raises questions about the tolerability of liraglutide in young children. Managing these side effects in a pediatric population can be challenging and may affect adherence.
- Lack of Consensus on BMI Reduction: There’s no international consensus on what constitutes a clinically meaningful BMI reduction in children, complicating the interpretation of the results.
Conclusion:
This trial provides preliminary evidence that liraglutide, combined with lifestyle interventions, may help reduce BMI in children under 12 with obesity. However, given the limitations—including small sample size, short duration, and safety concerns—it’s prudent to approach these findings with cautious optimism. More extensive studies with longer follow-up periods and more diverse populations are necessary to fully assess the long-term efficacy and safety of liraglutide in this vulnerable age group.
Takeaway:
While liraglutide shows promise as an adjunct therapy for pediatric obesity, it’s essential to weigh the benefits against the potential risks and uncertainties. Clinicians should continue to prioritize established lifestyle interventions and consider pharmacotherapy on a case-by-case basis, pending further evidence.