Semaglutide versus resmetirom for noncirrhotic MASH with moderate to advanced fibrosis: a cost-effectiveness analysis

Semaglutide, a glucagon-like peptide-1 receptor agonist, and resmetirom, a thyroid hormone receptor-β agonist, are approved therapies for noncirrhotic metabolic dysfunction–associated steatohepatitis (MASH) with moderate to advanced fibrosis. Their comparative economic value has not been established. To evaluate the cost-effectiveness of semaglutide and resmetirom compared with standard of care (SOC) in patients with noncirrhotic MASH and F2–F3 fibrosis. A state-transition model simulated disease progression in a hypothetical cohort with F2–F3 fibrosis over 5- and 10-year horizons from a U. S. healthcare payer perspective. Clinical efficacy inputs were derived from phase 3 trials (ESSENCE and MAESTRO-NASH), with costs and utilities obtained from published sources. Scenario analyses incorporated semaglutide’s cardiovascular mortality benefit. Deterministic and probabilistic sensitivity analyses assessed uncertainty. Semaglutide was cost-effective versus SOC at 5 years (ICER, 42, 200/QALY) and 10 years (ICER, 44, 138/QALY). Resmetirom produced higher ICERs (95, 981/QALY at 5 years; 107, 002/QALY at 10 years) but remained below a 150, 000/QALY threshold. Inclusion of cardiovascular mortality benefits improved semaglutide’s ICER to 38, 324/QALY. Probabilistic analyses showed semaglutide had the highest probability of cost-effectiveness across willingness-to-pay thresholds. Over a 10-year horizon, treatment of 100, 000 patients with F2–F3 MASH was projected to prevent 270 cases of decompensated cirrhosis, 10 cases of hepatocellular carcinoma, and 1, 040 liver-related deaths with semaglutide, compared with 310 cases of decompensated cirrhosis, 10 cases of hepatocellular carcinoma, and 1, 180 liver-related deaths with Resmetirom. Semaglutide demonstrated superior cost-effectiveness compared with SOC and resmetirom, with cardiovascular benefits further strengthening its economic value. Not applicable.