The development of obesity pharmacotherapy: from early challenges and setbacks to recognition by WHO

Obesity is a chronic, progressive disease associated with disability, increased morbidity, and reduced life expectancy. Global prevalence has risen sharply in recent decades, yet obesity and its treatment-particularly pharmacotherapy -have been highly stigmatised. A legacy of early medications withdrawn over safety concerns, together with poor efficacy, and widespread lack of recognition of obesity as a chronic disease contributed to persistent underuse of obesity pharmacotherapy. This underuse changed in the 2020s with GLP-1 receptor agonists and, later, multiagonist therapies, with their substantially greater efficacy, safety, and disease-modifying benefits compared with older agents. Reflecting this paradigm shift, WHO issued global guidelines and included GLP-1 receptor agonists in the Essential Medicines List, albeit for a narrowly defined population. We take a critical historical perspective, charting the highs and lows of obesity medication development and examining the scientific, regulatory, and societal factors that have slowed or impeded the translation of pharmacological advances into safe, effective, and widely accepted treatments for obesity.