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.