ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This meta-analysis including 415 children and adolescents with T2D showed that GLP-1 receptor agonists reduced HbA1c by 1%, fasting blood glucose, and body weight by 1.6 kg, with no notable impact on blood pressure. An increased incidence of mainly gastrointestinal side effects was observed.

Comment: Over the past decade, glucagon-like peptide 1 (GLP-1) receptor agonists have revolutionized the management of T2DM in adults.¹ These drugs not only improve glycemic control, but also promote weight loss, reduce the risk of major cardiovascular events and provide kidney protection. In contrast, trials in adolescents with T2D have demonstrated an improvement in HbA1c levels compared to untreated groups, but have not shown significant changes in BMI or blood pressure. This meta-analysis aimed to address the gaps by increasing sample size and statistical power, thereby providing more precise estimates of the effects of these interventions.

Five randomized clinical trials were included, encompassing a total of 415 patients, with follow-up ranging 5 to 26 weeks. Mean age ranged from 14.5 to 15.8 years, and two-thirds were females. Baseline mean HbA1c ranged 7.9% to 8.3%, mean body weight 89 kg to 101 kg, and mean body mass index (BMI) 34 to 37 kg/m².

In the meta-analysis, GLP-1 RA was found to lower HbA1c levels by -1%, and fasting glucose levels by 34 mg/dL. Only 3/5 studies reported data on body weight. While GLP-1 RA led to mean weight reduction of -1.6 kg compared to placebo, this change is marginal given the degree of obesity in this population. GLP-1 RA had no impact on blood pressure in adolescents. The limited number of trials for each GLP-1 RA makes it unclear if any medication is superior to another.

The limited weight loss among adolescents on GLP-1 receptor agonists is not fully understood. It is possible that the daily injections are burdensome, that socioeconomic circumstances are challenging, and the side effects significant. Adolescents in the intervention group had twice the odds of adverse effects, such as nausea, vomiting, and diarrhea. It is hoped that newer treatments - such as other GLP-1 receptor agonists, dual agonists triple combination therapies, and potent oral agonists — will offer better outcomes than those achieved with currently available agents

Reference: 1. Yao H, Zhang A, Li D, Wu Y, Wang CZ, Wan JY, Yuan CS. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis. BMJ. 2024 Jan 29;384:e076410. doi:10.1136/bmj-2023-076410.