Until recently, clinicians could only counsel lifestyle changes for patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH). Now, with the FDA’s approvals of semaglutide and resmetirom, treatment choices have expanded for patients whose disease has advanced to MASH.

1. An Increasingly Common Disease

   MASLD has emerged as a leading cause of chronic liver disease, driven by the increased prevalence of metabolic disorders such as diabetes and obesity.

2. The Power of GLP-1s

   The ESSENCE study, published in The New England Journal of Medicine, found that 2.4 mg of semaglutide once a week improved liver histology in patients with MASH and moderate or advanced fibrosis. GLP-1s, like semaglutide, may be appropriate for patients with coexisting obesity or diabetes, though gastrointestinal-related adverse effects and access issues could limit its use.

3. Resmetirom’s Targeted Approach

   Resmetirom acts directly on liver cells to improve lipid metabolism and may help reduce fibrosis. The MAESTRO-NASH trial, published in The New England Journal of Medicine, included adults with biopsy confirmed MASH and F2-F3 fibrosis and found resmetirom 80 mg and 100 mg produced MASH resolution without a worsening of fibrosis. Resmetirom is currently recommended only for patients with F2-F3 fibrosis. Gastrointestinal-related adverse effects are also common with this drug.

4. Matching Drug to Patient

   The choice of drug should be individualized on the basis of comorbidities. For example, GLP-1s, like semaglutide, may be beneficial for patients with coexisting diabetes or obesity, whereas resmetirom may be better suited for those with advanced liver disease, low BMI, or an inability to tolerate GLP-1s.

5. Future Research Directions

   More data are needed on long-term safety, cost-effectiveness, and optimal monitoring of treatment response. Studies are also needed in special populations, such as those with advanced renal disease or post-transplant.

Bottom line: Semaglutide and resmetirom offer new treatment options for patients with MASH, but they serve different roles. Clinicians should aim to match the drug to the patient’s comorbidities and disease stage, and stay alert to accessibility issues, tolerability, and evolving data.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.