ESSENCE
Trial question
What is the role of semaglutide in patients with MASH and moderate or advanced liver fibrosis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
57.0% female
43.0% male
N = 800
800 patients (457 female, 343 male).
Inclusion criteria: patients with MASH and moderate or advanced liver fibrosis.
Key exclusion criteria: chronic liver disease other than MASLD; hepatic decompensation; average alcohol consumption > 20 g/day for women and > 30 g/day for men; AST or ALT level > 5 times the ULN range at screening; eGFR < 30 mL/min/1.73 m²; glycated hemoglobin level > 9.5%; acute pancreatitis.
Interventions
N=534 semaglutide (subcutaneous dose of 2.4 mg once weekly for 240 weeks).
N=266 placebo (matching subcutaneous placebo once weekly for 240 weeks).
Primary outcome
Rate of resolution of steatohepatitis, as measured by NASH CRN fibrosis scale, without worsening of liver fibrosis after 72 weeks
62.9%
34.3%
62.9 %
47.2 %
31.4 %
15.7 %
0.0 %
Semaglutide
Placebo
Significant
increase ▲
NNT = 3
Significant increase in the rate of resolution of steatohepatitis, as measured by NASH CRN fibrosis scale, without worsening of liver fibrosis after 72 weeks (62.9% vs. 34.3%; AD 28.7%, 95% CI 21.1 to 36.2).
Secondary outcomes
Significantly greater reduction in liver fibrosis without worsening of steatohepatitis (36.8% vs. 22.4%; AD 14.4%, 95% CI 7.5 to 21.3).
Significant increase in combined resolution of steatohepatitis and reduction in liver fibrosis (32.7% vs. 16.1%; AD 16.5%, 95% CI 10.2 to 22.8).
Significantly greater reduction in mean body weight at week 72 (10.5% vs. 2%; MD 8.5, 95% CI 7.4 to 9.6).
Safety outcomes
No significant difference in serious adverse events.
Conclusion
In patients with MASH and moderate or advanced liver fibrosis, semaglutide was superior to placebo with respect to the rate of resolution of steatohepatitis, as measured by NASH CRN fibrosis scale, without worsening of liver fibrosis after 72 weeks.
Reference
Arun J Sanyal, Philip N Newsome, Iris Kliers et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025 Apr 30. Online ahead of print.
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