GLP-1 RAs have recently been approved in multiple jurisdictions for weight management in children without diabetes aged 12 and older. However, their safety and efficacy remain unclear. This systematic review and meta-analysis aimed to examine the safety and efficacy of GLP-1 RAs in children with obesity but without diabetes.

The authors searched the PubMed/MEDLINE, CENTRAL and Embase databases through May 2025 for randomized controlled trials of GLP-1 RAs in children without diabetes who had obesity. They assessed effects on weight, body mass index standard deviation score (BMI-SDS) (also known as BMI z-score), cardiometabolic outcomes (blood pressure, heart rate), health-related quality of life (HRQoL) and safety outcomes (adverse events). Two reviewers screened studies, extracted data and assessed bias.

Statistical analysis combined results from all included studies to estimate the average effect of GLP-1 medications compared with placebo or standard care. Primary outcomes focused on efficacy (e.g., weight and cardiometabolic effects), while secondary outcomes focused on safety.

A total of 1,095 studies were screened, and nine studies involving 756 participants were included. Four studies were considered small, with 12–44 participants and durations of 5–24 weeks. The other five were considered large, with 55–251 participants and durations of 52–68 weeks.

Three trials were conducted in the U.S., one in Germany, one across Sweden and Austria, and four involved international consortia. Three trials examined exenatide, five examined liraglutide and one examined semaglutide. Various GLP-1 RAs are approved for use in children aged 12 and older. The mean age of participants across this meta-analysis was 14–15 years, and the age range across all studies was 6–18 years.