Abstract

Pharmacological treatment for obesity has advanced significantly in recent years, particularly with the introduction of GLP-1 receptor agonists and other novel agents. However, an increasing number of patients fail to achieve clinically meaningful weight loss, highlighting the challenge of drug non-responsiveness. This review provides a comprehensive overview of the definition and evaluation of non-responders in obesity pharmacotherapy, explores the underlying pathophysiological mechanisms, and discusses clinical and therapeutic strategies to address this challenge. Potential contributors to non-response include inadequate medication adherence, genetic variability, gut microbiota dysbiosis, disordered eating behavior, and mental health conditions. Early identification of non-responders and the application of individualized treatment approaches are essential. Strategies such as behavioral interventions, cognitive behavioral therapy, drug switching, combination therapy, and consideration of bariatric surgery may improve treatment outcomes. Future research should focus on the development of predictive biomarkers and the integration of precision medicine approaches to enhance the effectiveness of obesity care.