Semaglutide and Tirzepatide Demonstrate Long-Term Cost-Effectiveness Among Patients With MASH
Key Takeaways:
- While the standard of care for metabolic dysfunction‐associated steatohepatitis (MASH) was the least expensive option, pharmacotherapies demonstrated increases in quality-adjusted life-years (QALYs).
- At a willingness-to-pay (WTP) threshold of $100 000 per QALY gained, semaglutide and tirzepatide yielded lower incremental cost‐effectiveness ratios (ICERs) than resmetirom, which exceeded the threshold.
- Drug prices were the main drivers of cost, illustrating the need for population-level pricing strategies aimed at reducing the economic burden associated with MASH.
MASH is associated with significant economic burden, and without intervention, patients may experience major liver-related complications and death. Therapies aimed at slowing disease progression during the F2 or F3 stages may improve patient outcomes and reduce health care costs.
Resmetirom was the first pharmacotherapy to be approved by the US Food and Drug Administration (FDA) to treat MASH, followed by semaglutide in 2025. Tirzepatide has also demonstrated promising clinical efficacy in phase 2 trial, though it has yet to receive FDA approval.
Study Methods and Outcomes
Researchers developed a Markov model to analyze the long-term cost-effectiveness of each pharmacotherapy compared with the standard of care for a hypothetical cohort of US adults with MASH with fibrosis stage F2 to F3.
Outcomes included QALYs and ICERs at a WTP threshold of $100 000 per QALY gained.
Pharmacotherapies vs Standard of Care
Compared to standard of care, the pharmacotherapies resmetirom, semaglutide, and tirzepatide increased the QALYs by 3.47, 3.04, and 4.46, respectively. However, standard of care had the lowest costs overall.
Resmetirom had an incremental cost of $948 743, resulting in an ICER of $273 445 per QALY, the highest of the pharmacotherapies and significantly exceeding the WTP threshold.
Semaglutide and tirzepatide demonstrated long-term cost-effectiveness. Semaglutide had an incremental cost of $243 094, resulting in an ICER of $80 076 per QALY. Tirzepatide had an incremental cost of $190 270, resulting in the lowest ICER ($42 705 per QALY).
At a smaller WTP threshold of $50 000, none of the pharmacotherapies were found to be cost-effective. Resmetirom, semaglutide, and tirzepatide would require cost reductions of approximately 79%, 33%, and 14%, respectively.
Drug costs were the biggest driver of ICER. However, findings for tirzepatide should be interpreted with caution as estimates were based on a network meta‐analysis of a phase 2 trial.
Implications for Managed Care
Semaglutide and tirzepatide demonstrated better cost-effectiveness compared to standard of care and resmetirom among patients with MASH at F2 to F3 stages of fibrosis.
Reducing the economic burden of MASH may require pricing and reimbursement strategies such as outcome-based contracts, indication-specific pricing, and volume-linked rebates
The authors said, “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.”
Reference
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
