MON-301 Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes in Children and Adolescents: A Meta-Analysis of Randomized Controlled Trials

Abstract V. Lins de Menezes: None. L. C Hespanhol: None. G. Alves: None. Introduction: The global epidemic of childhood obesity has led to a concerning rise in both the incidence and prevalence of type 2 diabetes (T2DM) among children and adolescents. Until recently, the approved treatments for pediatric patients encompassed only metformin and insulin. However, a notable shift occurred with the approval of liraglutide, a Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA), by regulatory agencies in the U.S. and Europe. Liraglutide was sanctioned as an adjunctive therapy for pediatric patients aged > 10 years already on metformin, with or without basal insulin. We performed a comprehensive systematic review and meta-analysis on the safety and efficacy of GLP-1 RA in treating T2DM among children and adolescents. Methods: We systematically searched PubMed, Embase, and Cochrane databases in December 2023 for randomized controlled trials (RCTs) that compared GLP-1 RA (exenatide, lixisenatide, dulaglutide, liraglutide or semaglutide) with placebo in patients from ages 8 to 19 years old, for the treatment of T2DM. Outcomes assessed were: (1) change from baseline in the glycated hemoglobin level (HbA1c); (2) change from baseline in the fasting glucose concentration; (3) changes from baseline in the BMI; and (4) adverse events. Statistical analyses were performed using RevMan 5.4.1 and R software. Heterogeneity was assessed with I² statistics and random-risk effect was used if I² > 50%. The protocol was registered in PROSPERO (ID: CRD42023482279). Results: Seven randomized studies involving 628 patients with T2DM were analyzed, comprising 272 (43.3%) who used GLP-1 RA and 356 (56.7%) who received placebo. In the GLP-1 RA group, there was a significant reduction in HbA1c (MD -0.98; 95% CI -1.24, -0.73; p <0.001; I² = 30%) compared to the placebo group. However, the change in fasting glucose concentration was higher in the GLP-1 RA group compared to the placebo group, albeit non-significantly (MD -4.55; 95% CI -9.30, 0.21; p = 0.06; I² = 73%). Likewise, there was a non-significant reduction in BMI in the GLP-1 RA group compared to the placebo group (MD -0.26; 95% CI -0.61, 0.09; p = 0.14; I² = 0%). Adverse events such as vomiting (RR 2.36; 95% CI 1.26, 4.45; p = 0.008; I² = 0%), diarrhea (RR 1.45; 95% CI 0.9, 2.35; p = 0.12; I² = 0%), and hypoglycemia (<54 mg/dl) (RR 2.16; 95% CI 1.07, 4.38; p=0.03; I² = 0%) were significantly more frequent in the GLP-1 RA group compared to placebo. Conclusion: In this meta-analysis of randomized trials, the use of GLP-1 RA in pediatric patients with T2DM yields significant reductions in HbA1c levels compared to placebo, indicating its potential as an effective adjunctive therapy. However, it's noteworthy that there were non-significantly changes in fasting glucose concentration and reduction in BMI compared to placebo. Monday, June 3, 2024