Semaglutide Dramatically Outperforms Resmetirom on Cost-Effectiveness for Liver Disease

Metabolic dysfunction-associated steatohepatitis (MASH) — formerly known as NASH — is a progressive liver disease driven by metabolic dysfunction, obesity, and insulin resistance. It carries a serious risk of cirrhosis, liver failure, and liver cancer, and represents an enormous and growing clinical and economic burden in the United States. Two drugs have now demonstrated meaningful efficacy in MASH: semaglutide 2.4 mg (a GLP-1 receptor agonist already approved for obesity) and resmetirom (a thyroid receptor beta agonist, the first FDA-approved MASH-specific drug). This study asks a timely question: which option delivers the best value for money?

Researchers from Novo Nordisk and Genesis Research Group constructed a cohort Markov state-transition model simulating disease progression over a lifetime horizon for patients with non-cirrhotic MASH and moderate-to-advanced fibrosis. Drawing on data from the ESSENCE trial (semaglutide) and MAESTRO-NASH trial (resmetirom), the model estimated quality-adjusted life years gained, costs, and key clinical outcomes. All costs were expressed in 2025 US dollars and discounted at 3% annually.

The base-case results were striking. Semaglutide produced 1.66 additional QALYs at an incremental cost of $33,031, yielding an ICER of approximately $19,911 per QALY — well below standard US willingness-to-pay thresholds of $50,000 to $150,000. Resmetirom 80 mg and 100 mg yielded ICERs of $346,810 and $198,607 per QALY, respectively. At a $150,000 WTP threshold, semaglutide was cost-effective in 99.5% of probabilistic simulations. A scenario using the direct consumer cash price of $499/month made semaglutide dominant — less costly and more effective than standard of care.

For clinicians and payers navigating MASH treatment decisions, these findings suggest semaglutide offers not only clinical benefit but exceptional economic value compared with the only FDA-approved MASH-specific therapy. However, the study was conducted entirely by Novo Nordisk employees and a contracted research group, creating a significant conflict of interest. Results should be interpreted with that in mind, and independent economic analyses will be essential to validate these conclusions.