ABSTRACT:
Obesity is a chronic, relapsing disease driven by multiple factors and stands as a major contributor to global morbidity and mortality. Its development involves an intricate interplay among genetic, epigenetic, metabolic, hormonal, environmental, and behavioral influences, causing wide variation in how patients present and respond to treatment. While lifestyle changes remain central to managing obesity, pharmacotherapy is now a core part of care for patients who cannot achieve or maintain meaningful weight loss through behavioral modifications alone. Yet standard drug approaches often rely on generalized strategies that overlook significant differences between individuals in drug efficacy, safety, tolerability, and long-term adherence. Recent progress in precision medicine has moved the field toward personalized pharmacotherapy, tailoring treatment choices to patient-specific traits such as obesity phenotype, metabolic profile, genetic background, co-occurring conditions, treatment goals, and personal preferences. The arrival of incretin-based therapies—specifically glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists—has greatly improved clinical outcomes, delivering deeper and more sustained weight loss alongside better control of obesity-related heart and metabolic complications. Beyond these drugs, progress in pharmacogenomics, biomarker discovery, digital health tools, artificial intelligence, and multimodal care models promises to refine individualized obesity management even further. This review explores the changing landscape of personalized obesity pharmacotherapy by looking at the scientific basis for precision treatment, currently available anti-obesity medications, patient phenotyping methods, pharmacogenomic tools, and emerging care algorithms. It also addresses practical hurdles such as variable treatment response, limited biomarker validation, access, cost, and long-term adherence, while pointing out future directions to help move care away from simple weight-focused management and toward tailored, mechanism-based approaches. Bringing precision medicine into everyday clinical practice can help optimize results, reduce side effects, and improve long-term disease management for people living with obesity.