MASH drug cost-effectiveness model

A 2026 U.S. cost-effectiveness model estimated that tirzepatide and semaglutide would each fall below a $100,000 per quality-adjusted life-year threshold when compared separately with standard care for metabolic dysfunction-associated steatohepatitis, or MASH, with F2 to F3 fibrosis. Resmetirom exceeded that threshold^[1]. These are modelled lifetime projections, not outcomes observed in a head-to-head clinical trial.

What the researchers modelled

The investigators built a Markov cohort model for a hypothetical group of U.S. adults with biopsy-confirmed MASH and stage F2 or F3 fibrosis. A Markov model moves a simulated cohort through defined health states over repeated cycles. This model used one-year cycles and a lifetime horizon, with 14 states spanning fibrosis regression and progression, compensated cirrhosis, decompensated cirrhosis, liver cancer, transplantation and death^[1].

The analysis took a U.S. healthcare payer perspective. Costs were expressed in 2024 U.S. dollars, and future costs and quality-adjusted life-years, or QALYs, were discounted by 3% per year. A QALY combines length and health-related quality of life into one modelled measure. The team evaluated resmetirom, semaglutide and tirzepatide separately against standard care^[1].

Treatment effects for MASH resolution and fibrosis improvement came from a Bayesian network meta-analysis rather than direct comparisons among all three medicines. The model used annual wholesale acquisition costs of $59,269 for resmetirom, $16,188 for semaglutide and $13,036 for tirzepatide. Those price inputs are central assumptions, not permanent market facts^[1].

The base-case estimates

Standard care produced an estimated 11.98 QALYs and lifetime cost of $54,948. Resmetirom produced 15.45 QALYs at $1,003,691, an incremental gain of 3.47 QALYs and incremental cost of $948,743. Its incremental cost-effectiveness ratio, or ICER, was $273,445 per QALY^[1].

Semaglutide produced an estimated 15.02 QALYs at $298,043. Against standard care, that was 3.04 additional QALYs for $243,095 in additional cost, giving an ICER of $80,076 per QALY. Tirzepatide produced 16.44 QALYs at $245,219, with 4.46 additional QALYs and $190,271 in additional cost, for an ICER of $42,705 per QALY^[1].

At the study's $100,000 per QALY willingness-to-pay threshold, the model therefore classified semaglutide and tirzepatide as cost-effective versus standard care and resmetirom as not cost-effective. Cost-effective does not mean cost-saving. Standard care remained the least expensive strategy, and each medicine increased projected spending^[1].

Price drove the ranking

One-way sensitivity analyses identified drug acquisition cost as the most influential variable for all three therapies. At a $100,000 per QALY threshold, the authors estimated that resmetirom's annual price would need to fall to about $23,007, 61% below the model's wholesale acquisition cost input. Semaglutide and tirzepatide stayed below that threshold at the prices used in the base case^[1].

The probabilistic analysis assigned tirzepatide a 99.5% probability and semaglutide an 89.8% probability of being cost-effective at $100,000 per QALY. Those percentages describe repeated simulations under the model's specified uncertainty distributions. They are not probabilities that an individual patient will benefit^[1].

Why this is not a treatment ranking

The authors did not perform a formal sequential incremental analysis across the active therapies. Each medicine was compared with standard care. That choice avoided presenting indirect network estimates as though they came from head-to-head trials, but it also means the ICER table cannot by itself identify one preferred treatment for a particular patient^[1].

Tirzepatide carries the largest evidence uncertainty in this model. Its MASH effect estimate came from a phase 2 trial and had wider credible intervals than estimates for the approved therapies. The paper also notes that tirzepatide did not have a U.S. MASH indication at the time of publication, so the model used an existing market price rather than a MASH-specific launch price^[1].

The model was intentionally liver-centred. It omitted established cardiovascular, mortality and weight-loss effects of GLP-1-based treatment, which the authors said may underestimate broader value for semaglutide and tirzepatide. At the same time, several transition probabilities came from older cohorts, early health states used optimistic utility values in the base case, and long-term projections necessarily extend beyond trial follow-up^[1].

How to read the result

The strongest conclusion is about the assumptions that matter: under this model, the combination of price and estimated liver benefit placed semaglutide and tirzepatide below a commonly used U.S. threshold. A different price, treatment duration, efficacy estimate, population or willingness-to-pay threshold can change the answer. The study informs payer policy; it does not replace evidence about safety, individual eligibility or comparative clinical outcomes.

For readers comparing the two incretin medicines, the semaglutide evidence overview and tirzepatide evidence overview cover their broader clinical evidence. A clinician must still match any treatment to diagnosis, approved indication, comorbidities, contraindications and coverage.

What remains unknown

Phase 3 confirmation and an indication-specific price are needed before tirzepatide's MASH estimate can be treated as stable. Direct comparative trials could reduce reliance on network assumptions. Longer follow-up is also needed to test whether histologic improvements translate into the projected reductions in cirrhosis, liver cancer, transplantation and mortality that drive lifetime value.

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