An efficient factorial design to optimize behavioral changes and improve health outcomes in adults prescribed next-generation obesity medications

About This Grant

PROJECT SUMMARY A new generation of anti-obesity medications (AOMs) have recently revolutionized the treatment of obesity. Critically, and in line with existing clinical guidelines for AOM use, clinical trials have evaluated these medications as an “adjunct to lifestyle intervention”; that is, all participants (whether randomized to placebo or study medication) received lifestyle intervention. There exists discordance, however, between the way that AOMs have been implemented in clinical trials (with lifestyle intervention) versus how they are implemented in clinical settings (with minimal follow-up focused on management of dosage and side effects). Furthermore, there is lack of clarity regarding whether patients prescribed second-generation AOMs benefit from behavioral lifestyle intervention and, if so, how much and what kind of lifestyle intervention is optimally beneficial. To address these critical questions, we propose to conduct a factorial experiment to optimize an individual-level lifestyle intervention for patients prescribed second-generation AOMs. We propose to recruit 608 adults with obesity (or overweight with a weight-related comorbidity) who are prescribed second-generation AOMs by their healthcare providers and, using an efficient 2x2x2x2x2 factorial trial design, randomize participants to receive (or not receive) each of 5 intervention components delivered over 12 months: 1) an individual Weight Loss 101 session including core weight loss education and behavioral skills training; 2) 3 individual coaching sessions delivered via telephone; 3) digital dietary self-monitoring and weekly automated feedback on calorie goal achievement; 4) digital physical activity self-monitoring and weekly automated feedback on activity goal achievement; and 5) digital weight self-monitoring and weekly automated feedback on weight trajectory. We propose to evaluate the efficacy of each intervention component for weight loss and identify an optimized program in which each component (or combination of components) contributes meaningfully to Month 12 weight loss outcomes (Aim 1). Importantly, we will also examine costs for each intervention component to inform future implementation. Under a precision medicine approach, we also propose to explore possible moderators (e.g., sex, race/ethnicity, age, income, nutrition literacy, rurality, level of social support, previous experience with lifestyle intervention, AOM type/dose and number of AOMs used) that might suggest different intervention protocols for specific subgroups. In addition, given the challenge of long-term weight loss maintenance, we also propose to examine weight loss maintenance at Month 24 (Aim 2). Other exploratory aims will investigate changes in body composition, health-related quality of life, hypothesized mediators such as treatment adherence, and additional health outcomes extracted from electronic health records; finally, we will explore AOM persistence and weight regain in participants who discontinue AOMs. This trial will result in an optimized behavioral intervention protocol for second-generation AOMs, supporting ideal implementation of these medications and development of new guidelines for the treatment of obesity.