GLP-1 Receptor Agonists in Metabolic Health: Expanding Applications, Weight Management, and Emerging Safety Considerations

GLP-1 receptor agonists (GLP-1 RAs) have transformed the treatment of type 2 diabetes mellitus (T2DM) and obesity and have recently gained an additional approved indication for metabolic dysfunction-associated steatohepatitis (MASH). Their expanding clinical use has also increased interest in off-label applications and their evolving safety profile. This narrative review summarizes current evidence regarding the off-label use of GLP-1 RAs and evaluates both well-established and emerging adverse effects. A literature search was performed using the PubMed database, and relevant studies addressing approved and off-label applications, efficacy, and safety were qualitatively analyzed. Current evidence suggests that GLP-1 RAs have therapeutic potential beyond approved indications, particularly in polycystic ovary syndrome, antipsychotic-induced weight gain, prediabetes, binge eating disorder, and disorders involving dysregulation of reward-related behavior. The most common adverse effects are gastrointestinal symptoms and gallbladder disorders, whereas emerging safety concerns include weight regain following treatment discontinuation, changes in body composition, hair loss, non-arteritic anterior ischemic optic neuropathy (NAION), and a theoretical risk of medullary thyroid carcinoma in susceptible individuals. Although these findings are promising, the available evidence remains heterogeneous. Further high-quality studies are required to establish the efficacy and long-term safety of off-label applications. Careful patient selection, appropriate monitoring, and integration of pharmacotherapy with lifestyle modification remain essential for optimizing clinical outcomes.