For years, the primary strategy for managing fatty liver disease, now often referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), centered on lifestyle modifications. However, the recent approval of the first-ever drug for a specific form of the condition—Resmetirom—has marked a new era in treatment options. While no single medication universally 'gets rid of' a fatty liver, a growing arsenal of pharmacological and lifestyle strategies can effectively manage and, in some cases, reverse the condition's progression.
The FDA's Approval: Resmetirom (Rezdiffra)
In March 2024, the U.S. Food and Drug Administration (FDA) granted accelerated approval to resmetirom (brand name Rezdiffra) for a specific patient population. It is indicated for adults with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), who have moderate-to-advanced liver fibrosis.
How Rezdiffra works
Rezdiffra is an oral, liver-targeted thyroid hormone receptor-beta (THR-β) selective agonist. This means it primarily acts within the liver to improve metabolic function without significantly affecting thyroid hormones elsewhere in the body. The key mechanisms include:
- Increasing Fat Metabolism: Activating THR-β promotes the breakdown of fat within the liver.
- Reducing Inflammation: It helps to decrease the inflammation associated with MASH.
- Improving Fibrosis: In clinical trials, the drug has been shown to reduce liver scarring (fibrosis) in a significant percentage of patients.
Efficacy and use
Clinical trials showed that Resmetirom led to both MASH resolution and fibrosis improvement in a notable portion of patients after 52 weeks. It is not a monotherapy but is intended for use in conjunction with a healthy diet and active lifestyle. Common side effects observed during trials include diarrhea and nausea, which are typically mild.
GLP-1 Receptor Agonists: A Multi-System Approach
Glucagon-like peptide-1 (GLP-1) receptor agonists, primarily used for type 2 diabetes and weight management, have demonstrated significant indirect benefits for fatty liver disease. Medications like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) can help to resolve MASH in some patients.
How GLP-1 agonists work
Unlike Resmetirom, which targets the liver directly, GLP-1 agonists work through broader, systemic effects. These include:
- Weight Loss: By slowing gastric emptying and increasing feelings of fullness, these drugs lead to reduced caloric intake and significant weight loss.
- Improved Blood Sugar: They enhance insulin sensitivity and lower blood glucose levels.
- Reduced Liver Fat: The combined effects on weight and metabolism significantly decrease fat accumulation and inflammation in the liver.
Notable options
- Semaglutide (Wegovy): In August 2025, the FDA approved Wegovy specifically for treating MASH in adults with moderate-to-advanced liver scarring.
- Survodutide: This dual agonist (GLP-1 and glucagon) showed promising phase 2 trial results for improving MASH and fibrosis.
Other Medications and Investigational Therapies
While Resmetirom is the only FDA-approved drug specifically for MASH, other drugs and nutritional supplements have been used off-label or are in clinical development.
- Pioglitazone (Actos): This thiazolidinedione (TZD) improves insulin sensitivity and has shown benefits in improving liver histology for MASH patients. However, side effects like weight gain and fluid retention limit its use.
- SGLT2 Inhibitors (Jardiance, Farxiga): These diabetes medications help the body excrete excess sugar, leading to weight loss and improved liver health. Studies show they can reduce liver fat and improve liver enzymes.
- Obeticholic Acid (OCA): An FXR agonist, OCA has shown some antifibrotic effects but was not approved by the FDA for MASH due to concerns over side effects, including severe itching and adverse lipid effects.
- Vitamin E: A meta-analysis showed that this antioxidant can improve some histological features in non-diabetic MASH patients. However, evidence regarding fibrosis is uncertain, and long-term use may pose risks.
- Future Treatments: A robust pipeline of drugs is in clinical trials, targeting various pathways in liver metabolism and fibrosis. These include FGF19/21 analogs and combinations of different drug classes.
The Cornerstone of Treatment: Lifestyle Changes
For any type of fatty liver disease, lifestyle modification remains the foundation of treatment, regardless of whether medication is also prescribed.
Key lifestyle changes include:
- Weight Loss: Losing at least 3-5% of body weight can reduce liver fat, while a 7-10% reduction can improve inflammation and fibrosis in MASH.
- Healthy Diet: A diet rich in fruits, vegetables, whole grains, and healthy fats is recommended. The Mediterranean diet, in particular, has shown efficacy. Avoiding sugary drinks and excessive fructose is crucial.
- Regular Exercise: Both aerobic exercise and resistance training are beneficial, even without significant weight loss.
- Limiting Alcohol: Reducing or eliminating alcohol intake is advised, as it can worsen liver damage.
Comparison of Key Treatments for MASH
| Feature | Resmetirom (Rezdiffra) | GLP-1 Agonists (e.g., Semaglutide) | Pioglitazone | Lifestyle Modifications |
|---|---|---|---|---|
| Approval Status | FDA-approved (MASH, moderate-advanced fibrosis) | Approved for diabetes and weight loss; also for MASH (Wegovy) | Approved for diabetes; used off-label for MASH | Standard of care |
| Primary Mechanism | Directly targets liver via THR-β receptor | Systemic metabolic improvement, weight loss | Improves insulin sensitivity | Calorie reduction, exercise |
| Impact on Fibrosis | Proven improvement in moderate-advanced fibrosis | Can improve or reverse fibrosis via weight loss | Can improve liver histology, including fibrosis | A 7-10% weight loss can reduce fibrosis |
| Common Side Effects | Diarrhea, nausea | Gastrointestinal issues (nausea, vomiting) | Weight gain, fluid retention | N/A (generally positive effects) |
| Best for | Non-cirrhotic MASH with significant fibrosis | Patients with concurrent obesity or type 2 diabetes | Select patients with MASH, often with T2DM | All patients with any stage of fatty liver disease |
Conclusion
The landscape of fatty liver disease treatment is evolving rapidly, offering new hope for those with advanced conditions like MASH. While the question of what drug gets rid of a fatty liver? has a more complex answer than a single pill, a combination of groundbreaking medications and well-established lifestyle changes provides a powerful and effective path forward. The FDA's approval of Rezdiffra demonstrates a significant step toward targeted pharmacological interventions, especially for patients with a higher risk of liver-related illness and death. For most individuals, however, the journey begins with weight loss, dietary improvements, and regular exercise, which remain the most impactful steps for improving liver health. Close consultation with a healthcare provider is essential to determine the most appropriate and personalized treatment plan.
The future of fatty liver treatment
Research continues to explore novel therapies, including combination approaches and drugs targeting new pathways. For example, some dual-agonist drugs are showing promise in clinical trials. The trend points toward personalized medicine, where specific drugs or combinations will be tailored to the individual's stage of disease and comorbidities, maximizing efficacy and minimizing side effects. This ongoing research holds great potential for further breakthroughs in the treatment of fatty liver disease in the coming years.
Authoritative Source
- American Association for the Study of Liver Diseases (AASLD) Guidelines: Provides comprehensive, evidence-based recommendations for the diagnosis and management of nonalcoholic fatty liver disease. (Note: These guidelines may not reflect the absolute latest drug approvals but remain a foundational resource.)
Further Considerations
- Diagnosis and Assessment: A proper diagnosis is crucial before initiating any treatment. This often involves blood tests, imaging (like MRI-PDFF), and sometimes a liver biopsy to determine the stage of fibrosis.
- Insurance Coverage: The cost and coverage of newly approved medications like Rezdiffra can be a significant consideration for patients. It is important to discuss these details with a healthcare provider and insurance company.
- Patient Compliance: Some treatments, especially those requiring regular injections or with significant side effects, may face challenges with long-term patient adherence. Lifestyle changes also require significant commitment.
