Once weekly semaglutide 2.4 mg led to resolution of steatohepatitis without worsening fibrosis in 62.9% of adults at week 72 versus 34.3% with placebo. Treatment is to be paired with a reduced-calorie diet and increased physical activity.

Metabolic dysfunction–associated steatohepatitis is a progressive liver disease frequently associated with overweight and obesity and often presents with few or no specific symptoms early, contributing to delayed diagnosis. The condition affects more than 250 million patients globally; an estimated 22 million patients live with the disease in the US.

The FDA decision was supported by part 1 of the phase 3 ESSENCE trial, which evaluated histologic outcomes at week 72 and showed superiority versus placebo for both primary measures. Improvement in liver fibrosis with no worsening of steatohepatitis occurred in 36.8% of patients receiving semaglutide and in 22.4% receiving placebo.

ESSENCE randomized 1,200 planned adults in a 2:1 ratio to once-weekly subcutaneous semaglutide 2.4 mg or placebo, in addition to standard care, for 240 weeks. Part 1 assessed biopsy-based liver histology at week 72 among the first 800 randomized patients. Part 2 is ongoing to determine whether semaglutide reduces liver-related clinical events through 240 weeks, with results expected in 2029. Based on part 1, regulatory submissions were filed in the European Union in February 2025 and in Japan in May 2025.

Wegovy is available in the US for this indication.

Source: Novo Nordisk