Phase 2 Trial: Survodutide Improves MASH Without Worsening Fibrosis, But Increases GI Side Effects – N Engl J Med

Study Design and Population: This 48-week, phase 2 randomized trial evaluated the efficacy and safety of survodutide, a dual agonist of the glucagon and GLP-1 receptors, in 293 adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis (F1-F3 stages). Participants were randomized to receive weekly injections of survodutide (2.4, 4.8, or 6.0 mg) or placebo.

Main Findings: Survodutide significantly improved MASH without worsening fibrosis compared to placebo, with 47% to 62% of participants in the survodutide groups achieving histologic improvement versus 14% in the placebo group. A reduction in liver fat content by at least 30% was observed in 57% to 67% of participants receiving survodutide, compared to 14% in the placebo group. However, adverse events such as nausea, diarrhea, and vomiting were more common with survodutide.

Implications for Practice: The findings suggest that survodutide could be a promising treatment for MASH, with potential benefits for liver histology and fat content. However, the increased gastrointestinal side effects warrant careful consideration in future phase 3 trials to better evaluate the drug’s safety profile and long-term efficacy.

Reference: Sanyal AJ, Bedossa P, Fraessdorf M, et al. (2024). A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. New England Journal of Medicine, 391(4), 311-319. DOI: 10.1056/NEJMoa2401755.