Glucagon-like peptide-1 receptor agonists lowered hemoglobin A1C, fasting glucose, body weight, body mass index, and systolic blood pressure in pediatric patients with obesity or type 2 diabetes, according to a systematic review and meta-analysis of randomized clinical trials. Gastrointestinal adverse events occurred more often with glucagon-like peptide-1 receptor agonists compared with placebo, while rates of depression and suicidal ideation did not differ.
Across 18 trials that included 1,402 patients aged 6 to 17 years, treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduced A1C by nearly half a percentage point overall and close to one point in type 2 diabetes trials. Fasting glucose decreased by about 10 mg/dL overall and more than 20 mg/dL in diabetes-only studies. Patients receiving treatment lost an average of 3 kg, with a nearly 5-kg reduction observed in obesity-focused trials. Body mass index (BMI) fell by more than one unit, while BMI percentile, waist circumference, and systolic blood pressure also declined.
Changes in lipid levels were minimal and not clinically meaningful. Adverse events were mainly gastrointestinal, including nausea and vomiting. Treatment discontinuations trended higher in the GLP-1 group, but rates of hypoglycemia, infections, hepatobiliary disorders, depression, and suicidal behaviors showed no meaningful differences compared with placebo.
The review included patients with obesity, type 2 diabetes, or prediabetes. The mean age was 13.7 years. Median treatment lasted about 6 months, with follow-up of about 2 months. Most trials allowed background lifestyle interventions, and some permitted concomitant metformin or insulin. Researchers applied random-effects models, and trial quality was assessed using the Cochrane risk of bias tool.
Limitations included variability across studies, short follow-up, and inconsistent reporting of psychiatric safety outcomes. Only 5 of the 18 trials used standardized measures of suicidality. Most trials were industry-sponsored, which may have influenced reporting.
“This extensive meta-analysis of 18 clinical trials evaluating the use of GLP-1 RAs in the pediatric population with diabetes or obesity offers a thorough synthesis of the benefits and risks associated with GLP-1 RAs in this underresearched group and may contribute to informed clinical decision-making,” wrote senior author Jingchuan Guo, MD, PhD, of the Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville.
Researchers concluded that GLP-1 RAs improved glycemic, weight, and cardiometabolic outcomes in pediatric patients, while gastrointestinal events remain an important consideration in long-term care.
Full disclosures can be found in the study.
Source: JAMA Pediatrics
