Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Obesity

Abstract

Background: Obesity treatment based on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) proved to limit morbidity and mortality in adult population. In children, optimizing lifestyle intervention (LSI) and reducing culpable environmental exposures represent the mainstay strategy for obesity prevention and management. However, there remains a subset of children and adolescents whose obesity is resistant to lifestyle approach. For these poor responders, the need for safe and effective weight-reducing agents is apparent. The purpose of this review is to provide an overview of the efficacy and safety of approved GLP-1 RA in the management of adult and pediatric obesity. Summary: We presented the main outcomes of clinical trial programs called SCALE and STEP that supported a market authorization approval for liraglutide and semaglutide for the treatment of obesity in adult population. Then, we summarized the studies on the efficacy of GLP-1 RA in pediatric obesity that have been accumulating from 2 larger studies with liraglutide and few other smaller studies with exenatide and liraglutide. The results indicate that GLP-1 RA is safe, tolerable, and effective in reducing weight and also in improving cardiometabolic profile in children with obesity and poor response to LSI alone. At present, liraglutide is the first and so far the only GLP-1 RA that received FDA approval in 2020 for use in children aged 12–17 years with obesity. New trials including semaglutide for pediatric obesity are ongoing. Key Messages: There is a strong interest in current use and further development of obesity treatments based on glucagon-like peptide-1 (GLP-1) agonism. In adolescents with obesity, who are poor responders to lifestyle approach, the use of GLP-1 RA as an adjunct to LSI is effective and safe. Due to limited experience, a general recommendation is to prioritize long acting over short acting GLP-1 RA because they are approved for the treatment of obesity and have better tolerability, safety, and treatment response effect. In the future research, more high-grade evidence including novel iterations of GLP-1 agonism and long-term follow-ups are needed in pediatric population.