NOTE: You must submit in Word format, not PDF, for eRA to update all the systems. The 2021 Food and Drug Administration (FDA) approval of the glucagon-like peptide 1 (GLP-1) receptor agonist, semaglutide (Wegovy), as an anti-obesity medication (AOM) is ushering in a radical shift in the treatment of obesity. Semaglutide is far more effective than prior rarely used AOMs and additional highly effective AOMs are expected in coming years. Considering that over 80 million Americans live with obesity (2020 prevalence of body mass index ≥30 kg/m2 among adults was 41.9%), obesity is a major health problem in the United States. AOMs are poised to become an important tool in population weight management but we have yet to understand how best to implement AOMs equitably and effectively in everyday practice. By carefully examining clinics within health systems that demonstrate varying use of AOMs, we will gain greater understanding of the barriers and facilitators to AOM use at various levels, including patient, provider, health system, and payer. Armed with these insights, we will be better equipped to develop effective strategies for optimizing the use of AOMs to maximize their population health benefits. We will engage a diverse array of stakeholders in a multi-site collaboration to detail the current state of AOM prescribing and implementation and to design tailored interventions based on best practices to optimize AOM access across health care settings. Our specific aims are to: Aim 1: Use data from 2009-2023 from the multi-site STAR PCORnet Network to understand the demographic, clinical and provider characteristics of eligible patients that are associated with AOM receipt. Aim 2: Identify key factors influencing AOM use at the patient, provider, and system levels. In-depth qualitative interviews will complement Aim 1 insights and help inform the development of a typology of implementation contexts specific to AOMs using the Tailored Implementation for Chronic Diseases framework. Aim 2a: Identify how patient attitudes towards AOMs and the steps required for obtaining an AOM prescription affect demand and access by conducting interviews with selected patients in multiple health systems. Aim 2b: Determine how health care provider and leader attitudes towards AOMs and their understanding of the obesity evaluation and treatment processes are barriers and facilitators to AOM use in three large health systems. Aim 2c: Determine how regional and national payers’ attitudes towards and understanding of the clinical and economic evidence for AOMs impact AOM coverage decisions. Aim 3: Design a Roadmap for selecting and designing implementation strategies to optimize AOM use that can be tailored to national, regional, and local barriers and facilitators; and then assess the feasibility, acceptability, and appropriateness of this Roadmap.