GLP-1 receptor agonists effectively reduce weight in adolescents with obesity; dual and triple incretins show future promise

Adolescent obesity is a growing global health crisis, significantly increasing risks for cardiovascular disease, type 2 diabetes mellitus, and long-term metabolic complications. While lifestyle interventions are foundational, their long-term effectiveness is often limited, driving interest in pharmacological solutions. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) and emerging dual/triple incretin therapies offer a promising mechanism to address this gap by modulating satiety, glucose homeostasis, and energy expenditure.

This narrative review evaluated the mechanisms, clinical efficacy, and safety of GLP-1R agonists, alongside dual and triple incretin-based therapies, for adolescent obesity. A literature search was conducted using PubMed and Scopus, focusing on clinical trials, systematic reviews, and real-world studies published between 2010 and 2024. Evidence from pediatric and adolescent populations was prioritized, with adult data included cautiously when adolescent-specific evidence was unavailable.

The review confirmed that single-agent GLP-1R agonists provide clinically meaningful weight reduction and metabolic benefits in adolescents. In the STEP TEENS trial, once-weekly semaglutide resulted in approximately 16% mean body weight reduction over 68 weeks, while liraglutide produced more modest reductions. Dual agonists such as tirzepatide and emerging triple agonists, including retatrutide, have shown superior weight-loss efficacy in adult populations; however, pediatric data for these agents remain limited or unavailable.

Across all incretin-based therapies, gastrointestinal adverse effects were the most commonly reported side effects, consistent with their known pharmacological profiles. These findings underscore the efficacy of current GLP-1R agonists while highlighting the potential of multi-receptor approaches.