Predictors of Weight Loss and Weight Loss Maintenance to Lifestyle Modification Therapy and Pharmacotherapy for Adolescents with Obesity

Project Summary/Abstract Neurobehavioral characteristics have the potential to predict initial weight loss and weight loss maintenance in response to various treatment approaches in adolescents with obesity. However, prior research is limited by heavy reliance on cross-sectional analyses and a focus on immersion-type interventions (e.g., inpatient treatment), which are not widely available. Identifying neurobehavioral predictors of response to clinically applicable treatments will stimulate needed progress in the emerging field of precision medicine. Building on a funded, randomized comparative effectiveness trial (R01-DK123273), the current study will prospectively examine neurobehavioral predictors of initial weight loss response and weight loss maintenance for adolescents with obesity participating in intensive lifestyle modification therapy (LMT) or low intensity LMT plus medical management using the glucagon-like peptide-1 receptor agonist (GLP1-RA), semaglutide. In the proposed study we will: 1) identify baseline neurobehavioral predictors of weight loss response in adolescents with obesity undergoing intervention; 2) for participants achieving >5% BMI reduction at 6 months (i.e. initial responders), identify neurobehavioral predictors of weight loss maintenance at 12; and 3) evaluate differences in predictors of response between intensive LMT and GLP-1RA therapy. This prospective, observational study will include 116 adolescents with obesity and will focus on the three main aspects of executive functions - inhibition, cognitive flexibility, and working memory – as well as reward responsivity using gold-standard measures. For each domain, a single factor (i.e., score) will be created from factor analysis and these latent factors will be used as predictors in the statistical models. To our knowledge, this will be the first study to evaluate neurobehavioral predictors of weight loss response to GLP-1RA therapy in adolescents. Moreover, we will be one of few who have prospectively evaluated neurobehavioral predictors of treatment response and weight loss maintenance for adolescents with obesity. Our overarching goal is to move beyond the current “one-size-fits-all” paradigm and understand how to best match adolescents with obesity to personally effective treatment, which will maximize clinical outcomes while minimizing exposure to unnecessary risks.