When You Can't Get Rezdiffra: What Are Your Options?

If you've been prescribed Rezdiffra (Resmetirom) but can't fill your prescription — whether due to insurance denials, cost, or availability issues — you're probably wondering: what else can I do?

The reality is that Rezdiffra is currently the only FDA-approved medication specifically for MASH (metabolic dysfunction-associated steatohepatitis). But that doesn't mean you're out of options. Several other medications are used off-label to manage MASH, and lifestyle changes remain a cornerstone of treatment.

In this article, we'll cover what Rezdiffra is, how it works, and the most promising alternatives available in 2026.

What Is Rezdiffra?

Rezdiffra is the brand name for Resmetirom, made by Madrigal Pharmaceuticals. It was approved by the FDA in March 2024 as the first treatment specifically for noncirrhotic MASH with moderate to advanced liver fibrosis (stages F2–F3).

It's prescribed alongside diet and exercise. The drug comes in three tablet strengths — 60 mg, 80 mg, and 100 mg — and is taken once daily. Dosing is based on body weight: 80 mg for patients under 100 kg and 100 mg for those 100 kg or more.

For full details, see our guide on what Rezdiffra is, its uses, and dosage.

How Does Rezdiffra Work?

Rezdiffra works by activating the thyroid hormone receptor-beta (THR-β) in your liver. This receptor plays a key role in how your liver processes fat. By stimulating THR-β, Rezdiffra helps:

• Reduce fat buildup in the liver (steatosis)
• Lower liver inflammation
• Slow or reverse liver scarring (fibrosis)

Importantly, Rezdiffra is selective — it targets THR-β in the liver without significantly affecting THR-α, which is active in the heart and bones. This selectivity is what makes it safer than older thyroid-based approaches.

For a deeper explanation, read our article on how Rezdiffra works: mechanism of action explained.

Why Might You Need an Alternative?

There are several common reasons patients look for alternatives to Rezdiffra:

• Insurance denial: Prior authorization may be denied, and appeals take time
• Cost: The list price is approximately $47,400 per year ($3,950/month)
• Availability: Rezdiffra is only available through specialty pharmacies
• Side effects: Some patients may not tolerate the medication
• Contraindications: Patients with decompensated cirrhosis cannot take Rezdiffra

Whatever the reason, it's important to work with your doctor to find the best approach for your situation.

Alternative Treatments for MASH in 2026

While none of the following medications are FDA-approved specifically for MASH, they have clinical evidence supporting their use and are commonly prescribed by hepatologists and gastroenterologists.

1. Pioglitazone

Pioglitazone is a thiazolidinedione (TZD) originally approved for type 2 diabetes. It improves insulin resistance — a key driver of MASH — and has been shown in clinical studies to improve liver inflammation and fibrosis in MASH patients.

Key facts:

• Available as a generic; costs as little as $4–$15 per month
• Typical dose: 30–45 mg once daily
• Benefits: Proven to reduce liver inflammation and steatosis
• Drawbacks: Can cause weight gain (3–5 kg), fluid retention, and increased fracture risk
• Best for: MASH patients with type 2 diabetes or insulin resistance

2. Vitamin E (High-Dose)

Vitamin E at high doses (800 IU/day) has shown benefits for MASH in non-diabetic patients. The landmark PIVENS trial demonstrated that Vitamin E improved steatohepatitis compared to placebo.

Key facts:

• Available over the counter; costs $10–$20 per month
• Typical dose: 800 IU daily
• Benefits: Reduces liver inflammation and fat
• Drawbacks: Long-term safety concerns, including a slightly increased risk of prostate cancer in men and hemorrhagic stroke at very high doses
• Best for: Non-diabetic adults with biopsy-proven MASH

3. Semaglutide (Ozempic / Wegovy)

Semaglutide is a GLP-1 receptor agonist approved for type 2 diabetes (Ozempic) and weight management (Wegovy). It has shown impressive results in clinical trials for MASH, with significant rates of MASH resolution and fibrosis improvement.

Key facts:

• Given as a weekly injection
• Costs vary widely: $900–$1,300/month without insurance, but often covered for diabetes or obesity
• Benefits: Strong evidence for MASH resolution, plus weight loss and cardiovascular benefits
• Drawbacks: GI side effects (nausea, vomiting), injectable only, not yet FDA-approved for MASH specifically
• Best for: MASH patients who also have type 2 diabetes or obesity

4. Obeticholic Acid (Ocaliva)

Obeticholic Acid is an FXR (farnesoid X receptor) agonist made by Intercept Pharmaceuticals. It was studied extensively for MASH and showed improvements in fibrosis, but did not receive FDA approval for MASH. It is approved for primary biliary cholangitis (PBC).

Key facts:

• Prescription only; expensive (around $6,000–$7,000/month for PBC indication)
• Benefits: Has shown fibrosis improvement in MASH trials
• Drawbacks: Causes pruritus (itching) in many patients, not approved for MASH, and the FDA issued a safety warning regarding liver injury risk in PBC patients
• Best for: Generally not recommended for MASH outside of clinical trials

Don't Forget Lifestyle Changes

Regardless of which medication you take — or even if you take none — lifestyle modifications are the foundation of MASH treatment. The American Association for the Study of Liver Diseases (AASLD) recommends:

• Weight loss: Losing 7–10% of body weight can significantly improve MASH
• Diet: A Mediterranean-style diet rich in fruits, vegetables, whole grains, and healthy fats
• Exercise: At least 150 minutes per week of moderate-intensity activity
• Avoid alcohol: Even small amounts can worsen liver disease

These changes can complement any medication and, in some cases, are enough to improve fibrosis on their own.

Final Thoughts

While Rezdiffra is the gold standard for MASH treatment in 2026, it's not the only path forward. If you can't access Rezdiffra right now, talk to your doctor about alternatives like Pioglitazone, Vitamin E, or Semaglutide — and double down on lifestyle changes that support your liver health.

And don't give up on Rezdiffra entirely. Check out our guides on how to find Rezdiffra in stock and how to save money on Rezdiffra — you may find a path to access that works for you.

Use Medfinder to check availability near you.