Data-driven prioritization of high-risk individuals for weight loss interventions.

New obesity medications have demonstrated efficacy in trials, but their real-world deployment is partly limited by the absence of approaches that identify individuals for treatment based on risks for obesity-related complications. Here we present a risk prediction model to guide prioritization of high-risk individuals. In a population-based sample of ~200,000 individuals with a body mass index (BMI) exceeding 27 kg m, our machine learning framework identified the 20 most informative features, from among thousands tested, that predict future onset of 18 complications of obesity, providing information beyond BMI. An integrated model (OBSCORE) successfully stratified individuals into risk groups based on incidence over 10 years: for example, 5.7%, 1.8%, 0.9%, 0.4% and 0.1% for cardiovascular mortality. We demonstrate generalizability of the model in independent populations of European and non-European ancestry and, in SURMOUNT-1 trial participants, show that weight loss was similar across baseline OBSCORE risk groups and that predicted risks decreased following treatment with tirzepatide. In summary, OBSCORE provides a framework for prioritizing high-risk individuals with overweight or obesity based on their risk of obesity-related complications, complementing BMI-based frameworks.