ESPE Abstracts

Background: Rates of pediatric obesity are on a concerning upward trajectory globally, with the prevalence approaching 1 in 5 children and adolescents aged 2-19 years in the United States. As a direct consequence of this obesity surge, we will continue to experience a substantial adult cardiometabolic burden. Although public health measures to optimize lifestyle interventions and reduce culpable environmental exposures are the primary target for governments and societies, there remains a subset of children and adolescents whose obesity is resistant to this approach.

Objectives: To determine the cardiometabolic and gastrointestinal effects of incretin-based therapies in children with obesity.

Study design: Web of Science, PubMed/MEDLINE, and Scopus databases from 01/01/1994-01/01/2021 for RCTs examining the cardiometabolic or gastrointestinal effects of incretin-based therapies (i.e., GLP-1 receptor agonists and DPP-4 inhibitors) in children and adolescents with obesity. Data were extracted by two independent surveyors and a random effects model was applied to meta-analyze generic inverse variance outcomes. Primary outcomes were related to cardiometabolic profile, while secondary outcomes of interest were gastrointestinal-related treatment-emergent adverse events.

Results: Nine studies involving 574 participants were identified, of which three involved exenatide and six involved liraglutide. No studies of relevance involving DPP-4I were identified. GLP-1RA use caused a modest reduction in body weight (mean difference [MD] -1.50 [-2.50, -0.50] kg, I²: 64%), BMI (MD -1.24 [-1.71, -0.77] kg/m², I²: 0%), and BMI z-score (MD -0.14 [-0.23, -0.06], I²: 43%). Interestingly, lifestyle interventions proved to be complimentary to these effects. Glycemic control was improved in children with proven insulin resistance (HbA1c MD -1.05 [-1.93, -0.18]%, I²: 76%). Although no lipid profile improvements were noted, a modest decrease in systolic blood pressure was detected (MD -2.30 [-4.11, -0.49] mmHg; I²: 0%). Finally, analysis of gastrointestinal-related treatment-emergent adverse events revealed an increased rate of nausea (risk ratio 2.11 [1.44, 3.09]; I²: 0%), without significant increases in other gastrointestinal symptoms or pathology.

Conclusions: This meta-analysis indicates that GLP-1RAs are safe and effective in modestly reducing weight, HbA1c and systolic blood pressure in children and adolescents with obesity in a clinical setting, albeit with increased rates of nausea.

PROSPERO: CRD42020195869.