Impact of Fibrotic Metabolic Dysfunction–Associated Steatohepatitis as a New Indication on Semaglutide Eligibility in the US Adult Population

Background and Aims: Semaglutide, a glucagon-like peptide-1 receptor agonist, is effective in the treatment of fibrotic (F2-F3) metabolic dysfunction-associated steatohepatitis (MASH) and has recently received accelerated Food and Drug Administration approval. However, the extent to which this new indication expands treatment eligibility beyond existing approvals for type 2 diabetes mellitus (T2DM) and obesity remains unclear. Methods: We analyzed 6936 community-dwelling adults from the National Health and Nutrition Examination Survey 2017 to 2020 cohort study after excluding individuals with viral hepatitis or excessive alcohol consumption. Semaglutide eligibility was defined according to Food and Drug Administration-approved indications for weight loss, high-risk T2DM, or fibrotic MASH. Findings were validated in the Mainz biopsy cohort (n = 213) with biopsy-proven metabolic dysfunction-associated steatotic liver disease and F2-F3 fibrosis. Results: In the US general population, 51.5% met indications for semaglutide therapy for weight loss or high-risk T2DM. Among individuals with metabolic dysfunction-associated steatotic liver disease, 80.9% qualified for treatment based on conventional indications, increasing to 95.4% in those with fibrotic MASH. Including fibrotic MASH as an additional indication raised the overall eligibility marginally from 51.5% to 51.8%. Aligning with these findings from the general population, we found that 80.3% of patients with biopsy proven F2-F3 fibrosis were eligible for semaglutide irrespective of fibrotic MASH. Conclusion: Semaglutide eligibility is high in the US general population and the new fibrotic MASH indication largely overlapped with pre-existing indications. The findings highlight the close overlap between metabolic comorbidities and liver disease and emphasize the need for an integrated, patient-centered approach to semaglutide, alongside policies that improve access and reimbursement.