Dual Agonists for Management of Metabolic Dysfunction–Associated Steatohepatitis

This editorial discusses the promise of dual agonists tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide receptor agonist) and survodutide (GLP-1/glucagon receptor agonist) for treating metabolic dysfunction associated steatohepatitis (MASH), a prevalent liver disease with limited therapeutic options. Two phase 2 trials demonstrated significant histologic improvements: tirzepatide achieved MASH resolution without worsening fibrosis in up to 62% of patients and fibrosis improvement in 50%, while survodutide showed similar efficacy but higher discontinuation rates due to adverse events (e.g., gastrointestinal symptoms). Both agents also induced substantial weight loss (10–16%). However, limitations include small sample sizes, underrepresentation of marginalized groups, and unanswered questions about long term use and efficacy in cirrhosis. The findings underscore the potential of dual agonists to address MASH but highlight the need for larger, longer term studies to optimize safety and accessibility.

This editorial discusses the promise of dual agonists tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide receptor agonist) and survodutide (GLP-1/glucagon receptor agonist) for treating metabolic dysfunction associated steatohepatitis (MASH), a prevalent liver disease with limited therapeutic options. Two phase 2 trials demonstrated significant histologic improvements: tirzepatide achieved MASH resolution without worsening fibrosis in up to 62% of patients and fibrosis improvement in 50%, while survodutide showed similar efficacy but higher discontinuation rates due to adverse events (e.g., gastrointestinal symptoms). Both agents also induced substantial weight loss (10–16%). However, limitations include small sample sizes, underrepresentation of marginalized groups, and unanswered questions about long term use and efficacy in cirrhosis. The findings underscore the potential of dual agonists to address MASH but highlight the need for larger, longer term studies to optimize safety and accessibility.