A Cost-Effectiveness Model of Semaglutide 2.4 mg, Resmetirom 80 mg, and Resmetirom 100 mg Versus Standard of Care for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis in the United States

In a modelled US cost-effectiveness analysis, semaglutide 2.4 mg was cost effective versus standard of care for non-cirrhotic MASH with moderate to advanced fibrosis, with a cost per QALY gained well below common willingness-to-pay thresholds. It added 1.66 quality-adjusted life years at an incremental cost of US$33,031, while the two resmetirom regimens had much larger incremental cost-effectiveness ratios.

Journal article — Cost-effectiveness Markov state-transition model. Population: Patients with non-cirrhotic MASH with moderate to advanced fibrosis in the US. Follow-up: Lifetime horizon. Interventions: semaglutide 2.4 mg; resmetirom 80 mg; resmetirom 100 mg.

In the base case, semaglutide 2.4 mg added 1.66 QALYs at an incremental cost of US$33,031 versus standard of care, giving an ICER of US$19,911 per QALY gained. Resmetirom 80 mg and 100 mg added 1.20 and 1.24 QALYs at incremental costs of US$415,110 and US$245,991, with ICERs of US$346,810 and US$198,607 per QALY gained, respectively. At a willingness-to-pay threshold of US$150,000, semaglutide 2.4 mg was cost effective in 99.5% of simulations. In a scenario analysis using the direct-to-consumer cash price for semaglutide 2.4 mg of US$499 per month, semaglutide was less costly and more effective than standard of care. Sensitivity analyses confirmed the robustness of the findings.

Researchers working on semaglutide will find this paper relevant because it adds a US payer cost-effectiveness estimate for semaglutide 2.4 mg in non-cirrhotic MASH with moderate to advanced fibrosis and positions it economically against resmetirom. It does not establish efficacy or safety on its own; it is a modelled analysis based on published trial data, and each drug was compared with standard of care rather than head-to-head.

Key findings

Semaglutide 2.4 mg produced an additional 1.66 QALYs at an incremental cost of US$33,031 versus standard of care.
Semaglutide 2.4 mg had an incremental cost-effectiveness ratio of US$19,911 per QALY gained versus standard of care.
Resmetirom 80 mg and 100 mg had incremental cost-effectiveness ratios of US$346,810 and US$198,607 per QALY gained, respectively.
At a willingness-to-pay threshold of US$150,000, semaglutide 2.4 mg was cost effective in 99.5% of simulations.
In a scenario analysis using a direct-to-consumer cash price of US$499 per month, semaglutide 2.4 mg was less costly and more effective than standard of care.

Limitations

Model-based analysis relies on published literature and clinical trial transition probabilities, so the outputs depend on those external inputs.
The US third-party payer perspective may not generalise to other countries or healthcare settings.
No direct head-to-head comparison between semaglutide and resmetirom was modelled; each was evaluated separately against standard of care.

The record

Journal: PharmacoEconomics
Published: 2026-07-26
PMID: 42503575 — DOI: 10.1007/s40273-026-01647-8
Author countries: USA

Peptide profiles: Semaglutide.

All indexed evidence: Semaglutide trials & papers.