GLP-1 Receptor Agonists in Adolescents Raise Concerns for Bone Health, Reproductive Safety, and Eating Disorder Risk

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in adolescents for obesity and type 2 diabetes mellitus (T2DM), with growing interest in polyendocrine metabolic ovarian syndrome (PMOS). Adolescence is a critical period for peak bone mass acquisition, yet the long-term implications of pharmacologic weight loss on skeletal development remain underexplored. Furthermore, the potential for these potent appetite suppressants to exacerbate eating disorders or impact future reproductive health in this vulnerable population warrants careful consideration.

This commentary systematically examined emerging concerns regarding bone health, reproductive safety, eating disorder risk, and endocrine development associated with GLP-1 RA use in adolescent populations. The authors synthesized existing evidence from both adult and adolescent clinical trials, focusing on liraglutide and semaglutide, to highlight areas where data is limited or absent. The review specifically addressed the theoretical impact of rapid pharmacologic weight loss on bone mineral accrual and the psychosocial vulnerabilities unique to adolescents.

While adult studies demonstrate improvements in weight loss, insulin resistance, and menstrual regularity with GLP-1 RA therapy, and adolescent trials of liraglutide and semaglutide show significant weight reduction without short-term effects on growth or pubertal development, critical gaps remain. Adolescence is a vital period for peak bone mass acquisition, and rapid pharmacologic weight loss may theoretically impair bone mineral accrual. Evidence from adult populations suggests modest reductions in bone mineral density associated with weight loss, though structured exercise may mitigate these effects. Crucially, GLP-1 RAs are not recommended during pregnancy, and no data exist on reproductive outcomes following adolescent exposure. Additionally, the potent appetite-suppressing effects of these agents raise concerns about potential misuse or exacerbation of eating disorders in adolescents, a population uniquely vulnerable to body image pressures. The commentary highlights that while GLP-1 RAs are promising adjunct therapies, long-term skeletal, reproductive, and psychological impacts require further investigation.

Adult studies show modest reductions in bone mineral density with weight loss, but no data exist on reproductive outcomes following adolescent GLP-1 RA exposure.