EQ-5D health utility gains with once-weekly semaglutide 2.4 mg in people with MASH and F2/F3 fibrosis: An analysis of ESSENCE.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of metabolic dysfunction-associated steatotic liver disease. It is highly prevalent, particularly among individuals with overweight or obesity, and substantially impairs health-related quality of life. Semaglutide 2.4 mg received accelerated approval from the US FDA in August 2025 for adults with noncirrhotic MASH and fibrosis stages F2-F3 based on results from the ESSENCE trial. This study aimed to estimate the impact of semaglutide on health utility in this population.

METHODS

This exploratory analysis used Week 72 data from ESSENCE Part 1, a Phase III, randomized, double-blind, placebo-controlled trial. Adults with biopsy-confirmed MASH and fibrosis stage F2 or F3 were randomized 2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo plus standard of care. EuroQol 5-‍Dimension (EQ-5D) utilities were mapped from Short Form-36 (SF-36) scores using the Rowen et al. (2009) algorithm. Change from baseline was analyzed with treatment, baseline diabetes status, and fibrosis stages as covariates.

RESULTS

A total of 800 participants were included in this analysis (semaglutide 2.4 mg n = 534; placebo n = 266). Mean age was 56.0 years; 57.1% were female; mean body mass index was 34.6 kg/m2 and 55.9% had type 2 diabetes. Baseline mapped EQ-5D utility was approximately 0.78 in both groups. At Week 72, semaglutide significantly improved mapped EQ-5D utility vs. placebo (estimated treatment difference 0.03; 95% CI 0.01-0.06; nominal p = 0.0015), with consistent effects across fibrosis stages.

CONCLUSIONS

In adults with MASH and F2 or F3 fibrosis, once-weekly semaglutide 2.4 mg was associated with statistically significant improvements in mapped EQ-5D health utility vs. placebo. These exploratory findings provide utility estimates that may help to inform cost-effectiveness evaluations and health technology assessments.

IMPACT AND IMPLICATIONS: This study provides the first estimates of EuroQol 5-Dimension (EQ-5D) health utility gains associated with once-weekly semaglutide 2.4 mg in people with metabolic dysfunction-associated steatohepatitis (MASH) and F2/F3 fibrosis. The findings are important for payers and clinicians because they demonstrate a statistically significant improvement in mapped EQ-5D health utility with semaglutide 2.4 mg over 72 weeks. These results can directly inform cost-effectiveness models and support healthcare decision-making by quantifying the health-related quality of life benefits of semaglutide using a widely accepted preference-based metric. Given the use of mapped rather than directly measured utilities and the UK-specific tariff, the results should be interpreted with appropriate caution.