A Breakthrough in Liver Fibrosis Treatment
For years, patients facing liver fibrosis—scarring of the liver tissue—had limited treatment options beyond managing the underlying cause, such as viral hepatitis, alcohol abuse, or Metabolic Dysfunction-Associated Steatohepatitis (MASH). MASH, formerly known as non-alcoholic steatohepatitis (NASH), is the more severe form of fatty liver disease, leading to inflammation and cellular damage. The recent Food and Drug Administration (FDA) approval of two distinct medications has revolutionized the treatment landscape for MASH-related liver fibrosis, offering new hope for many patients. The drugs, Rezdiffra (resmetirom) and Wegovy (semaglutide), target different aspects of the disease and are used alongside a healthy diet and increased physical activity.
Rezdiffra (Resmetirom): A Targeted Oral Therapy
In March 2024, the FDA granted accelerated approval to Rezdiffra (resmetirom), the first medication specifically indicated for adults with noncirrhotic MASH and moderate-to-advanced liver fibrosis (stages F2 and F3).
How Resmetirom Works
Resmetirom is a daily oral pill that acts as a thyroid hormone receptor-beta (THR-β) selective agonist. This targeted action helps to:
- Reduce liver fat accumulation: It directly affects how the liver metabolizes fat.
- Decrease inflammation: By activating the THR-β receptor, it reduces the inflammatory response within the liver.
- Improve scarring: Clinical trials showed that Resmetirom was effective at resolving MASH or improving fibrosis by at least one stage in a significant portion of patients compared to a placebo.
Who is an Ideal Candidate?
Rezdiffra is intended for adults with MASH who have progressed to notable liver scarring but have not yet developed cirrhosis. It must be used in conjunction with diet and exercise. Patients with certain medical histories, such as decompensated cirrhosis, are not candidates for this treatment. It is important to discuss potential drug interactions, especially with certain cholesterol-lowering statins, with a healthcare provider.
Wegovy (Semaglutide): A Dual-Action Injectable
Building on its success as a weight-management drug, Wegovy (semaglutide) received accelerated FDA approval in August 2025 for treating MASH with moderate-to-advanced liver fibrosis. Wegovy is a weekly injection.
How Semaglutide Works
As a glucagon-like peptide-1 (GLP-1) receptor agonist, semaglutide primarily acts by:
- Promoting weight loss: This directly addresses one of the key metabolic drivers of fatty liver disease.
- Improving insulin sensitivity: It helps regulate blood sugar, a significant factor for MASH patients who often have type 2 diabetes.
- Reducing inflammation: Beyond weight loss, it has additional, not fully understood, mechanisms that contribute to improved liver health.
Why Wegovy is a Major Development
For many patients, Wegovy offers a two-pronged approach, simultaneously managing weight and targeting the liver's inflammatory and scarring processes. Clinical trial results indicated a high rate of MASH resolution without worsening fibrosis after 72 weeks of treatment. This broader metabolic effect can also benefit other conditions associated with MASH, such as cardiovascular disease. Like Rezdiffra, Wegovy is prescribed alongside a reduced-calorie diet and increased physical activity.
Comparing Rezdiffra and Wegovy
| Feature | Rezdiffra (Resmetirom) | Wegovy (Semaglutide) |
|---|---|---|
| Drug Type | Thyroid hormone receptor-beta (THR-β) agonist | Glucagon-like peptide-1 (GLP-1) receptor agonist |
| Mechanism | Targets liver metabolism directly to reduce fat and inflammation | Promotes weight loss and improves systemic metabolic health |
| Administration | Oral pill, taken daily | Subcutaneous injection, taken weekly |
| Primary Indication | MASH with F2/F3 fibrosis | MASH with F2/F3 fibrosis |
| Associated Benefit | Specific liver-focused metabolic improvement | Systemic benefits, including significant weight loss |
| Common Side Effects | Diarrhea, nausea | Nausea, diarrhea, vomiting |
The Role of Lifestyle and Ongoing Research
It is crucial to remember that both Rezdiffra and Wegovy are intended to be used in combination with lifestyle modifications. Diet and exercise remain the foundation of MASH management and are essential for maximizing the benefits of these new medications.
Beyond these two approved drugs, the field of hepatology is thriving with innovative research. Several other potential anti-fibrotic agents are in various stages of clinical trials:
- FGF21 Analogues: Drugs like Pegozafermin are being studied for their potential to improve MASH and fibrosis.
- Galectin-3 Inhibitors: Belapectin, for instance, has been explored for its anti-fibrotic properties, particularly for cirrhosis.
- Dual-purpose Agents: Other GLP-1 receptor agonists and drugs like Efruxifermin and Survodutide continue to be investigated for their efficacy in tackling both MASH and associated fibrosis.
These ongoing studies highlight a robust pipeline of new pharmacological strategies aimed at not only slowing but potentially reversing liver fibrosis. The ultimate goal is to offer patients a chance to restore liver health and prevent progression to end-stage liver disease, reducing the need for transplants.
Conclusion
The FDA approvals of Rezdiffra and Wegovy represent a monumental step forward in the treatment of liver fibrosis caused by MASH. For the first time, patients with moderate-to-advanced liver scarring have medication options that directly target the disease process. Rezdiffra offers a liver-specific metabolic intervention, while Wegovy provides a dual-action approach tackling both metabolic health and liver inflammation. These breakthroughs, combined with the continued importance of lifestyle changes, offer a future where liver fibrosis can be effectively managed and potentially reversed, significantly improving patient outcomes and quality of life.
Visit the American Liver Foundation for more resources and information on liver health.
