NIDDK Workshop: Real-World Evidence Essential for GLP-1RA Regulatory, Clinical, and Coverage Decisions

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed obesity and diabetes management, with rapidly expanding indications and use. However, key questions persist regarding optimal treatment pathways, long-term safety, effectiveness across diverse populations, and economic impact. Traditional randomized controlled trials (RCTs) often lack the scope to capture rare adverse events or real-world adherence. Real-world evidence (RWE) derived from electronic health records and claims offers a promising approach to address these gaps, making its integration into decision-making crucial.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) convened a workshop in May 2025 with experts from regulatory agencies, guideline committees, payers, and academia. Discussions focused on identifying knowledge gaps in GLP-1RA use, evaluating how RWE informs practice, assessing limitations of real-world data, and strategies to reduce bias in RWE. Presentations emphasized RWE's potential to complement randomized trials by capturing rare adverse events, long-term outcomes, and effectiveness in routine care.

The workshop identified several unique challenges complicating the use of RWE for GLP-1RA therapies, including inconsistent insurance coverage, high discontinuation rates, medication shortages, compounded formulations, and off-label prescribing. Participants noted that persistent challenges include data reliability, confounding, and incomplete capture of medication use and outcomes, particularly in pediatric and underserved populations. Despite these hurdles, the consensus was that robust RWE is essential for developing value-based coverage policies and optimizing GLP-1RA use. Continued investment in high-quality data infrastructure and analytic methods will be critical to inform regulatory, clinical, and economic decisions as utilization expands.

Coverage decisions for GLP-1RAs remain heterogeneous across Medicare, Medicaid, and private payers and across time, underscoring the need for rigorous cost-benefit analyses.