1033-OR: Early Weight Loss Velocity Guides Precision Escalation in Obesity Treatment

Introduction and Objective: Effective obesity management requires identifying non-responders early to prevent therapeutic inertia. We aimed to: (1) compare the predictive accuracy of baseline profiling versus early dynamic weight loss markers; and (2) validate a clinical decision rule for escalating treatment to GLP-1 RAs or ketogenic diets (VLCKD). Methods: We analyzed a retrospective cohort of 8,450 adults with obesity prescribed a Mediterranean diet (ICANS). We modeled 24-month trajectories using Joint Latent Class Models to account for attrition. XGBoost models predicted non-response using baseline characteristics versus 1-month weight loss velocity. The rule was validated in an independent cohort (N=573) using Target Trial Emulation to compare 12-month outcomes of Standard Care versus Early Intensification. Results: Modeling identified a dominant “Early Attrition” phenotype (69%). Baseline profiling (demographics, HOMA-IR, lipids, psychometrics) failed to identify these patients (AUC 0.57). Conversely, incorporating 1-month weight loss velocity achieved high accuracy (AUC 0.91). A practical cutoff of <1.5% weight loss/month achieved >90% sensitivity. In validation, high-risk patients on Standard Care achieved a median 12-month weight loss of only 1.4%. Those switched to Intensified Therapy achieved 7.9% loss (Cohen’s d=1.08, p<0.01). Low-risk patients achieved clinically meaningful loss (10.2%) on Standard Care. Conclusion: Baseline profiles are insufficient for predicting dietary success. However, the physiological response at 1 month effectively integrates biological complexity to predict outcomes. A dynamic monitoring strategy using a 1.5% monthly weight loss threshold reliably identifies non-responders who benefit from early escalation. Disclosure A. Foppiani: None. F. Sileo: None. B. Marelli: None. A. Battezzati: None. Funding Project funded under the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3 - Call for proposals No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union – NextGenerationEU; Award Number: Project code PE00000003, Concession Decree No. 1550 of 11 October 2022 adopted by the Italian Ministry of University and Research, CUP D93C22000890001, Project title “ON Foods - Research and innovation network on food and nutrition Sustainability, Safety and Security – Working ON Foods.