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Life sciences · Journal article
Frontiers in Endocrinology · October 23, 2026
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease worldwide, driven by increasing obesity and type 2 diabetes mellitus. The expanding use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) raises an epidemiological question: could therapies targeting these metabolic drivers reshape the future burden of chronic liver disease? GLP-1-based therapies reduce body weight and improve metabolic dysfunction, with potential implications for hepatic steatosis and disease progression. The phase 3 ESSENCE trial demonstrated histological benefits of semaglutide in metabolic dysfunction-associated steatohepatitis (MASH) with moderate-to-advanced fibrosis, supporting accelerated or conditional regulatory approvals. However, effects on liver-related clinical outcomes remain unproven. In this Perspective, we examine the evidence and translate it into an explicitly parameterized scenario using a potential impact fraction. Combining published estimates of eligibility, relative risk, treatment persistence, and effectiveness with coverage scenarios of 5%, 10%, and 20%, the model suggests relative reductions of approximately 0.3% to 1.1% in the global incidence of cirrhosis among individuals with prevalent MASLD, at equilibrium (95% uncertainty interval at 20% coverage and intermediate persistence, 0.6% to 1.6%; best-case envelope, 4.6%). These estimates represent testable hypotheses rather than established clinical effects. Effective coverage, defined as coverage multiplied by persistence, is the principal constraint. We identify observations that would refute these expectations and discuss implications for prevention, healthcare systems, and the natural history of MASLD. Population benefits will depend on sustained treatment, accessibility, affordability, and equitable implementation, alongside confirmation that histological improvements translate into fewer liver-related clinical events.