Semaglutide 2.4 mg improved liver markers at BMI under 27 in post hoc analysis of Phase 3 ESSENCE
In 106 adults with MASH and fibrosis, weekly semaglutide lowered ALT and AST versus placebo at 72 weeks, a post hoc analysis of Novo Nordisk's ESSENCE trial showed.
At The Liver Meeting 2026, the annual meeting of the American Association for the Study of Liver Diseases in Denver, new clinical data were presented on metabolic dysfunction-associated steatohepatitis (MASH) in people with lower body weight, ad-hoc-news.de reports. A post hoc analysis of Part 1 of Novo Nordisk's Phase 3 ESSENCE trial, reported on 8 November 2026, found that semaglutide 2.4 mg once weekly improved liver parameters in patients with a BMI below 27 kg/m². ad-hoc-news.de
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The analysis drew on the 72-week interim data. Of 800 randomized participants, 106 adults with MASH and liver fibrosis had a BMI under 27 kg/m². The full ESSENCE design includes 1,197 patients with fibrosis stages F2 and F3, randomized 2:1, over 240 weeks. In the US, semaglutide 2.4 mg has FDA accelerated approval for MASH with moderate to advanced fibrosis without cirrhosis.
Liver and fibrosis markers at 72 weeks
Compared with placebo, the estimated treatment ratio (ETR) for alanine aminotransferase (ALT) was 0.61 (95% CI 0.48–0.79). For aspartate aminotransferase (AST) the ETR was 0.67 (95% CI 0.56–0.80).
The FAST score showed an estimated treatment difference (ETD) of −0.13 (95% CI −0.26 to −0.01), and the Enhanced Liver Fibrosis (ELF) score an ETD of −0.45 (95% CI −0.73 to −0.17). The collagen marker PRO-C3 had an ETR of 0.82 (95% CI 0.71–0.95). For liver stiffness by VCTE-LSM the ETR was 0.88 (95% CI 0.73–1.06); this interval includes 1.0. ad-hoc-news.de
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Semaglutide 2.4 mg is contraindicated in medullary thyroid carcinoma and in multiple endocrine neoplasia syndrome type 2. Worldwide, more than 250 million people have MASH; an estimated 90% are undiagnosed, and over 80% of patients have obesity. According to estimates from University Hospital Regensburg, 20–30% of adults in German-speaking countries have metabolic dysfunction-associated steatotic liver disease (MASLD), and normal-weight people make up about 7–20% of them.
Real-world data from retrospective studies
On 6 November 2026, two retrospective analyses from clinical practice were presented. PLATINUM-Truveta used records from 30 US health systems between June 2021 and March 2026 and compared 2,873 MASH patients on semaglutide with 2,285 on resmetirom. At six months AST fell by 10.4 versus 4.5 (p<0.001), while the ALT decrease of 14.8 versus 11.6 was not statistically significant (p=0.20).
HbA1c fell by 0.38 versus 0.08 percentage points, and body weight by 18.9 lb (8.6 kg, about 8%) versus 5.6 lb (both p<0.001). Platelets rose by 7.8 versus a fall of 4.4 (p=0.022). LDL cholesterol dropped by 29.1 on resmetirom versus 13.7 on semaglutide (p<0.001). ad-hoc-news.de
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The 12-month RHODIUM-2 observational study compared 2,479 semaglutide patients with 70,702 controls. ALT fell by 14.0 versus 3.8 (difference −10.5; p<0.01), AST by 9.1 versus 1.8 (−7.3; p=0.001), and weight by 30.7 lb versus 2.4 lb (−28.4; p<0.001). HbA1c fell by 0.46 versus 0.09 percentage points. Both real-world studies were retrospective and non-randomized, so they do not provide direct evidence of causality.
