A new systematic review and meta-analysis published in JAMA Pediatrics provides the most comprehensive evidence to date on the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in children and adolescents with obesity or type 2 diabetes. The analysis of 18 randomized clinical trials involving 1,402 participants aged 6 to 17 years demonstrates significant clinical benefits while addressing safety concerns in this vulnerable population.
Clinical Efficacy Demonstrated Across Multiple Parameters
The meta-analysis revealed that GLP-1 RAs were effective in significantly improving several key clinical outcomes compared to placebo. Participants receiving these medications showed reductions in hemoglobin A1c levels, fasting glucose, body weight, body mass index (BMI), BMI standard deviation score, BMI percentile, and systolic blood pressure. These changes represent meaningful improvements in both glycemic control and cardiometabolic health, addressing the urgent global health concerns posed by pediatric obesity and type 2 diabetes.
The clinical significance of these findings is underscored by the current prevalence of obesity, which now affects one in five young people and raises the risk of developing diabetes and long-term cardiometabolic complications.
Safety Profile Shows Manageable Side Effects
In terms of safety, the analysis found that gastrointestinal side effects such as nausea, vomiting, and diarrhea were significantly more common among those taking GLP-1 RAs compared to placebo. However, other adverse outcomes including depression, suicidal thoughts or behaviors, hepatobiliary disorders, hypoglycemia, and treatment discontinuation did not differ significantly between the treatment and placebo groups.
This safety profile is particularly important given previous concerns about the long-term psychiatric safety of GLP-1 RAs, which were not supported by the evidence in this analysis. The findings suggest that while gastrointestinal side effects remain an important consideration, particularly for long-term use, the overall safety profile appears manageable in pediatric populations.
Expert Perspectives on Study Limitations
Professor Naveed Sattar, Professor of Cardiometabolic Medicine at the University of Glasgow, noted important limitations of the current analysis. "This paper is of only modest interest as although obesity levels are rising fastest in younger people, the present meta-analysis looks predominantly at trials with older GLP-1RAs known to give much lower weight loss than higher doses of semaglutide and tirzepatide, the two most recent licensed drugs of most interest to pediatricians," Sattar explained.
The weight loss achieved with older medicines shown in this meta-analysis was described as "rather modest," though Sattar acknowledged that "the reported safety reports thus far are reassuring." He emphasized the need for ongoing trials with newer agents in children with type 2 diabetes and called for more safety assessments including impacts on growth and puberty.
Broader Treatment Context
Sattar also highlighted the broader context of pediatric obesity treatment, noting that "we cannot solve childhood obesity by drugs alone – prevention by changing the obesogenic environment is the key, but incredibly hard to do as no country has really solved this issue."
The analysis represents an important step in understanding the role of GLP-1 RAs in pediatric populations, though the trials analyzed were relatively short in duration. The findings suggest that these treatments may play a valuable role in improving health outcomes in high-risk pediatric populations, while continued research is needed to assess the durability of benefits and ensure safe, equitable use of these therapies in children and adolescents.
