Semaglutide 2.4 mg in Participants With Metabolic Dysfunction‐Associated Steatohepatitis: Baseline Characteristics and Design of the Phase 3 ESSENCE Trial

BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated potential beneficial effects in metabolic dysfunction-associated steatohepatitis (MASH). AIMS: To describe the trial design and baseline characteristics of the 'Effect of Semaglutide in Subjects with Non-cirrhotic Non-alcoholic Steatohepatitis' (ESSENCE) trial (NCT04822181). METHODS: ESSENCE is a two-part, phase 3, randomised, multicentre trial evaluating the effect of subcutaneous semaglutide 2.4 mg in participants with biopsy-proven MASH and fibrosis stage 2 or 3. The primary objective of Part 1 is to demonstrate that semaglutide improves liver histology compared with placebo. The two primary endpoints are: resolution of steatohepatitis and no worsening of liver fibrosis, and improvement in liver fibrosis and no worsening of steatohepatitis. The Part 2 objective is based on clinical outcomes. The current work reports baseline characteristics of the first 800 randomised participants which includes demographics, laboratory parameters, liver histology, non-invasive tests and presence of metabolic dysfunction-associated steatotic liver disease (MASLD) cardiometabolic criteria. RESULTS: , 55.5% had type 2 diabetes and > 99% had at least one MASLD cardiometabolic criterion according to the published definition. CONCLUSION: The ESSENCE baseline population includes participants with clinically significant fibrosis stages 2 and 3. Although MASLD cardiometabolic criteria were not a requirement for study enrolment, almost all participants (> 99%) had at least one MASLD cardiometabolic criterion. TRIAL REGISTRATION: NCT04822181.