Efficacy and safety of zalfermin co-administered with semaglutide in participants with fibrosis and cirrhosis due to metabolic dysfunction-associated steatohepatitis: a phase 2, dose-ranging, double-blind, randomised controlled trial.

Semaglutide 2·4 mg significantly improved liver fibrosis without worsening steatohepatitis in patients with fibrosis and cirrhosis, unlike the zalfermin combination.

• Why it matters: Effective treatments for metabolic dysfunction-associated steatohepatitis with advanced fibrosis or cirrhosis are limited, highlighting the need for therapies that can modify disease progression.
• What they did: A phase 2, double-blind, randomized trial assessed 698 participants receiving various doses of zalfermin, semaglutide, cagrilintide, or placebo over 52 weeks, measuring liver fibrosis improvement without disease worsening.
• The result: While the zalfermin and semaglutide combination did not significantly outperform placebo, semaglutide alone showed a nominally significant benefit, suggesting it warrants further investigation as a potential therapy.