Drug Price Drives Value of MASH Therapies More Than Efficacy

Tirzepatide (Zepbound; Eli Lilly) and semaglutide (Wegovy; Novo Nordisk) were cost-effective for metabolic dysfunction–associated steatohepatitis (MASH) with moderate to advanced fibrosis at current US prices, but resmetirom (Rezdiffra; Madrigal Pharmaceuticals) was not, exceeding a common willingness-to-pay threshold by more than 2-fold, according to a recent modeling study published in Diabetes, Obesity and Metabolism.¹

New MASH Therapies Arrive With Wide Price Gaps

MASH, which can advance to fibrosis, cirrhosis, and hepatocellular carcinoma, is now the second leading indication for liver transplantation in the US. Resmetirom became the first approved therapy for MASH with F2-F3 fibrosis in 2024, at an annual wholesale acquisition cost (WAC) of $47,400.² Semaglutide followed in August 2025.³ By contrast, tirzepatide is not FDA-approved for MASH, though its histologic benefit has been demonstrated in a phase 2 trial.¹

Despite the availability of these treatment options, investigators noted that cost remains a significant barrier to adoption; they added that the long-term value of these agents had not been compared within a single framework. To inform payer decision-making and guide equitable access for high-risk patients, the researchers conducted a study to evaluate the cost-effectiveness of all 3 therapies.

Specifically, they built a lifetime Markov model from the US payer perspective, simulating a cohort of 50-year-old adults with biopsy-confirmed MASH and F2-F3 fibrosis. Treatment effects came from a Bayesian network meta-analysis that anchored each therapy to placebo for fibrosis improvement and MASH resolution. Each drug was compared individually with the standard of care against a threshold of $100,000 per quality-adjusted life-year (QALY).

Tirzepatide, Semaglutide Fall Below Cost-Effectiveness Threshold

Tirzepatide added 4.46 QALYs at an incremental cost of $190,270, yielding an incremental cost-effectiveness ratio (ICER) of $42,705 per QALY. Semaglutide added 3.04 QALYs at $243,094, for an ICER of $80,076 per QALY. By contrast, resmetirom added 3.47 QALYs but at an incremental cost of $948,743, producing an ICER of $273,445 per QALY.

In probabilistic sensitivity analysis across 10,000 simulations, the likelihood of cost-effectiveness at $100,000 per QALY was 99.5% for tirzepatide, 89.8% for semaglutide, and 0% for resmetirom. Over a shorter 10-year horizon, however, semaglutide's ICER rose to $137,422 per QALY, while tirzepatide's remained below the threshold at $54,405.

Drug cost was the most influential variable for all 3 agents, the researchers noted. The model used annual costs of $59,269 for resmetirom, $16,188 for semaglutide, and $13,036 for tirzepatide; tirzepatide was priced at its obesity-indication WAC since no MASH-specific price exists. They added that the economic ranking of the 3 drugs reflects pricing differences as much as efficacy differences.

Threshold pricing analyses showed resmetirom would need to cost roughly $23,007 per year, a 61% reduction, to meet the $100,000 per QALY benchmark. At a stricter $50,000 threshold, all 3 agents would require price cuts of approximately 79%, 33%, and 14%, respectively. Resmetirom's ICER fell below $100,000 only at about 37% annual discontinuation, or under a 2-year treatment cap. The authors said these findings reflect cumulative drug costs rather than support for short-course therapy.

Findings Put Pricing at the Center of MASH Access

The investigators estimated that treating only eligible US adults with biopsy-confirmed F2-F3 MASH could exceed $10 billion in annual spending, drawing parallels to the budget strain and access restrictions that followed curative hepatitis C therapies. As a result, they proposed outcomes-based contracts, indication-specific pricing, and volume-linked rebates to balance manufacturer and payer incentives.

They also acknowledged several of the model’s limitations, including that it was deliberately liver-centric and excluded the cardiovascular, all-cause mortality, and weight-loss benefits of glucagon-like peptide-1 receptor agonists, likely understating the value of semaglutide and tirzepatide. Tirzepatide's estimates also carry added uncertainty because they rely on phase 2 data with wider credible intervals.

Lastly, the authors warned that current price disparities could worsen metabolic health inequities, since MASH disproportionately affects people with obesity, type 2 diabetes, and lower socioeconomic status.

"Drug pricing, not clinical efficacy, will ultimately determine the real-world impact of pharmacologic therapy and the growing burden of MASH," they wrote. "Aligning clinical innovation with value-based pricing and equitable access is critical to ensure that the advent of effective therapy translates into population-level health gains rather than widening disparities in metabolic liver disease."

References

1. Abdeen AA, Ayer T, Biswas A, Wehrle CJ, Laique SN, Aminian A. Cost-effectiveness of pharmacologic therapies for metabolic dysfunction–associated steatohepatitis with significant fibrosis in the United States. Diabetes Obes Metab. 2026;28(9):8378-8389. doi:10.1111/dom.71020
2. Joszt L. FDA approves resmetirom, first treatment for NASH with liver fibrosis. AJMC^®. March 14, 2024. Accessed September 29, 2026. https://www.ajmc.com/view/fda-approves-resmetirom-first-treatment-for-nash-with-liver-fibrosis
3. Klein HE. FDA approves semaglutide for MASH with fibrosis. AJMC. August 18, 2025. Accessed September 29, 2026. https://www.ajmc.com/view/fda-approves-semaglutide-for-mash-with-fibrosis