The pharmacotherapy for pediatric obesity: insights and challenges from adult weight-loss medications.

Abstract

Obesity significantly increases the risk of developing other chronic diseases and shortens the life expectancy by 5 to 8 years. Childhood obesity is particularly prominent as 80% of teenagers with obesity have shown it to persist into adulthood. With reference to the development of adult medication, the present review summarises the recent research progress in the development of pediatric anti-obesity drugs. The current management guidelines support the use of medication for adolescents aged 12 and above when lifestyle measures are ineffective. Early weight-loss drugs like the serotonergic agonist fenfluramine and the norepinephrine reuptake inhibitor sibutramine were withdrawn due to severe safety issues. Rainbow pills and the CB₁ inhibitor rimonabant also failed over neuropsychiatric toxicity. These highlighted inadequate safety profiling in initial development, and there were almost no studies on children. Recently, GLP-1 receptor agonists, such as semaglutide, and the dual-target agonist tirzepatide have gained popularity among adults and adolescents with obesity. However, it still faces significant limitations, including the long-term neurodevelopmental safety of adolescents, high costs and limited insurance coverage, and widespread gastrointestinal side effects. It is foreseeable that the focus of adult weight loss medication research may gradually shift to multi-target new drugs, including the dual agonist mazdutide and the triple receptor agonist retatrutide. Therefore, the development of pediatric weight loss drugs should also focus on the GLP-1 receptor agonists and multi-target new drugs. In addition, there is an urgent need to verify the safety and efficacy of approved weight loss medications through pediatric clinical trials.