GLP-1 Receptor Agonists in Adolescents: Emerging Endocrine, Reproductive, and Psychosocial Concerns

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed to adolescents for obesity and type 2 diabetes mellitus (T2DM), with growing interest in extending their use to conditions such as polyendocrine metabolic ovarian syndrome (PMOS, formerly known as polycystic ovary syndrome or PCOS). However, adolescence represents the critical window for peak bone mass acquisition, and the implications of pharmacologic weight loss during this developmental period have received limited attention. Furthermore, this commentary addresses potential concerns related to eating disorder risk and future reproductive outcomes in this population.

This commentary examines the emerging concerns regarding bone health, reproductive safety, eating disorder risk and endocrine development when GLP-1 RAs are used in adolescent populations.

Adult studies demonstrate improvements in weight loss, insulin resistance, and menstrual regularity with GLP-1 RA therapy. In adolescents with obesity, clinical trials of liraglutide and semaglutide show significant weight reduction without short-term effects on growth or pubertal development. However, adolescence represents a critical 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, while structured exercise may mitigate these effects. 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.

GLP-1 RAs represent a promising adjunct therapy for adolescents with obesity, T2DM, and PMOS, but long-term skeletal, reproductive, psychological, and endocrine outcomes remain uncertain. Careful patient selection, bone health monitoring, incorporation of resistance exercise, contraceptive counseling, and screening for disordered eating may be essential when these therapies are considered in adolescent populations.