2610-P: Pathophysiological Obesity Phenotype–Guided Evaluation of Efficacy and Safety for GLP-1RA

Introduction and Objective: To evaluate the efficacy and safety of GLP-1RA in Chinese individuals with obesity among different pathophysiological obesity phenotypes. Methods: 845 patients with obesity scheduled for GLP-1RA treatment were phenotyped as hungry brain, hungry gut, emotional eating, and low metabolism. The primary endpoint was weight loss percentage from baseline to 12 months. Exploratory outcomes included changes in hunger and depression scores, body composition, and laboratory parameters. Results: Weight loss percentages by GLP-1RA were comparable among four obesity phenotypes, with a mean value of -15.1% (95% CI -16.3 to -14.0) from baseline to 12 months. Conversely, pathophysiological outcomes showed phenotype-specific patterns: by 12 months, the hungry brain phenotype demonstrated greater reduction in 30min postprandial hunger scores (-38.2±25.2, P<0.001); by 9 months, superior 120min postprandial hunger score reductions were observed in hungry brain (-26.3±32.1) and hungry gut (-25.2±27.1) compared with low metabolism (-1.3±24.4, P<0.001); by 9 months, depression scores showed a greater reduction in emotional eating (-3.4±2.6) versus hungry brain (-1.0±2.6) and low metabolism (-1.6±2.9) (P<0.001). Conclusion: Despite of the comparable weight loss mediated by GLP-1RA across phenotypes, phenotype-specific improvements in hunger and mood aligned with underlying pathophysiological mechanisms, supporting phenotype-guided obesity management.