A New Era in Fatty Liver Treatment
For years, the management of fatty liver disease, now known as metabolic dysfunction-associated steatotic liver disease (MASLD), relied primarily on lifestyle changes like diet and exercise. However, this approach is often insufficient for patients with the more severe and progressive form of the condition, metabolic dysfunction-associated steatohepatitis (MASH). MASH causes inflammation and scarring (fibrosis) that can lead to cirrhosis and liver failure. The recent FDA approval of two groundbreaking medications has ushered in a new era of targeted pharmacological treatment for this previously underserved patient population.
Rezdiffra (Resmetirom): A Direct Liver Approach
In March 2024, the FDA granted accelerated approval to Rezdiffra, a medication developed by Madrigal Pharmaceuticals. This was a landmark moment, as it was the first drug specifically approved for MASH with moderate to advanced liver fibrosis.
How Rezdiffra works
Rezdiffra's active ingredient, resmetirom, is a selective thyroid hormone receptor-beta (THR-β) agonist. By activating this receptor, which is predominantly expressed in the liver, the drug helps improve liver metabolism, increases the breakdown of fat, and reduces inflammation. This targeted action helps address the core metabolic issues driving the disease progression.
Efficacy and approval
Rezdiffra's accelerated approval was based on positive results from a 52-week, Phase 3 clinical trial.
Important considerations
Rezdiffra is indicated for adults with non-cirrhotic MASH and moderate to advanced fibrosis (F2-F3) and should be used with diet and exercise. Common side effects are often temporary. It is not for patients with decompensated cirrhosis.
Wegovy (Semaglutide): A Systemic Treatment
Following Rezdiffra, Wegovy (semaglutide) received FDA approval for treating MASH in adults with moderate-to-advanced fibrosis in August 2025. Originally known as a powerful weight loss and diabetes medication, its efficacy in treating liver disease is a welcome development.
How Wegovy works
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It primarily works by regulating insulin and blood sugar, slowing stomach emptying, and suppressing appetite, leading to weight loss. By addressing the underlying metabolic dysfunction associated with obesity and type 2 diabetes—major drivers of MASH—Wegovy can significantly improve liver inflammation and scarring.
Efficacy and approval
Wegovy's approval was based on a Phase 3 trial showing significant MASH resolution.
Other Drugs in the Pipeline
The success of Rezdiffra and Wegovy has reinvigorated the development of MASH treatments. Other promising therapies are in various stages of clinical trials:
- Lanifibranor: A pan-PPAR agonist with anti-inflammatory and anti-fibrotic effects, currently in Phase 3 trials with results expected in late 2026.
- Survodutide: A dual glucagon and GLP-1 receptor agonist from Boehringer Ingelheim and Zealand Pharma that showed strong Phase 2 results.
- ION224: An antisense oligonucleotide DGAT-2 inhibitor being developed by Ionis Pharmaceuticals, which showed promising Phase 2 data in 2025.
Rezdiffra vs. Wegovy: Key Differences
| Feature | Rezdiffra (resmetirom) | Wegovy (semaglutide) |
|---|---|---|
| Mechanism | Selective thyroid hormone receptor-beta (THR-β) agonist, directly targets liver metabolism. | Glucagon-like peptide-1 (GLP-1) receptor agonist, works systemically to promote weight loss and metabolic control. |
| Route of Administration | Oral tablet. | Injectable. |
| Primary Effect | Reduces liver fat accumulation, inflammation, and scarring. | Addresses underlying metabolic issues like obesity and type 2 diabetes, leading to MASH improvement. |
| Weight Impact | Not a weight-loss drug, though lifestyle modification is required. | Significant weight loss is a primary effect. |
| Approval | Accelerated approval based on 52-week data (March 2024). | Accelerated approval based on 72-week data (August 2025). |
| Side Effects | Diarrhea, nausea, vomiting, gallstone-related conditions. | Nausea, diarrhea, vomiting, abdominal pain. |
Conclusion
The approvals of Rezdiffra and Wegovy mark a turning point for patients with metabolic-associated steatohepatitis (MASH). For the first time, pharmacological treatments offer a direct way to address the inflammation and fibrosis caused by fatty liver disease, rather than solely relying on lifestyle changes. Rezdiffra acts directly on the liver's metabolism, while Wegovy targets the systemic metabolic issues often linked to the condition. These options, alongside a robust pipeline of other potential therapies, provide significant hope for a condition that previously had no approved drug treatment. As research continues, and long-term efficacy data becomes available, the landscape of fatty liver treatment will continue to evolve, offering better outcomes for millions of affected individuals.
Learn more about metabolic dysfunction-associated steatohepatitis (MASH) from the NIH
