How Rezdiffra Works: A Plain-English Explanation

Rezdiffra (Resmetirom) works by selectively activating a thyroid hormone receptor in the liver called THR-β, which helps reduce liver fat, calm inflammation, and slow the scarring (fibrosis) caused by NASH/MASH — without significantly affecting the heart, bones, or other organs.

If that sounds like a lot of medical jargon, don't worry. This article breaks down exactly what Rezdiffra does in your body, how long it takes to work, and what makes it different from other approaches to treating liver disease.

What Rezdiffra Does in Your Body

To understand how Rezdiffra works, it helps to know a little about thyroid hormones and your liver.

The Thyroid-Liver Connection

Your thyroid gland produces hormones that regulate your metabolism — how your body processes fats, sugars, and energy. These hormones work by binding to special receptors in your cells. There are two main types:

• THR-α (alpha) — Found mostly in the heart, bones, and muscles. Activating this receptor too much can cause problems like rapid heart rate and bone loss.
• THR-β (beta) — Found mainly in the liver. Activating this receptor helps the liver burn fat, reduce inflammation, and clear out triglycerides.

In NASH/MASH, the liver is overwhelmed with excess fat. This triggers inflammation, which over time causes fibrosis (scarring). Think of it like a kitchen sponge that's been soaked in grease — it can't do its job properly, and the buildup eventually damages the sponge itself.

How Rezdiffra Targets the Problem

Rezdiffra is a selective THR-β agonist — meaning it specifically activates the thyroid hormone receptor in the liver without meaningfully activating THR-α in the heart and bones. Here's what that means in practical terms:

• Reduces liver fat: By turning on THR-β, Rezdiffra signals the liver to process and burn stored triglycerides more efficiently. Think of it like turning up the thermostat in the liver's fat-burning furnace.
• Reduces inflammation: Less fat in the liver means less damage to liver cells, which leads to less inflammation. Rezdiffra also appears to have direct anti-inflammatory effects.
• Slows fibrosis: With less ongoing damage, the liver's scarring process slows down and may even partially reverse.

The key innovation is selectivity. Older thyroid hormone treatments couldn't target just the liver — they affected the whole body, causing side effects like heart problems and bone loss. Rezdiffra was designed from the ground up to avoid those issues.

How Long Does Rezdiffra Take to Work?

Rezdiffra is not an overnight fix. In clinical trials, improvements were measured over 52 weeks (about one year) of treatment. Here's what patients can expect:

• Liver fat reduction: Measurable decreases in liver fat (as seen on imaging) may begin within a few months, but the full benefit develops over time.
• Fibrosis improvement: Improvement in liver fibrosis — the primary goal of treatment — was assessed at the 52-week mark in clinical trials. Some patients saw a one-stage improvement in fibrosis.
• Lab markers: Changes in liver enzymes and lipid levels may be noticeable within the first few months of treatment.

It's important to keep taking Rezdiffra as prescribed, even if you don't "feel" different right away. NASH/MASH is a slow-progressing disease, and the medication works gradually alongside diet and exercise.

How Long Does Rezdiffra Last in Your System?

Rezdiffra is taken once daily, meaning its effects are maintained with consistent daily dosing. The drug is designed to be taken continuously as long as your doctor recommends. If you stop taking it, its effects will gradually wear off — liver fat may begin to reaccumulate over time.

This is similar to how blood pressure or cholesterol medications work: they manage the condition as long as you take them, but they're not a one-time cure.

What Makes Rezdiffra Different from Similar Medications?

Before Rezdiffra, there were no FDA-approved medications for NASH/MASH. Doctors relied on off-label treatments and lifestyle changes. Here's how Rezdiffra compares to the most commonly discussed alternatives:

Rezdiffra vs. Pioglitazone

Pioglitazone is a diabetes medication sometimes used off-label for NASH. It improves insulin sensitivity and has shown some benefit for liver inflammation, but it often causes weight gain and fluid retention — problematic for patients who already struggle with metabolic syndrome. Rezdiffra targets liver fat directly through a completely different mechanism and does not cause weight gain.

Rezdiffra vs. Vitamin E

High-dose Vitamin E has been used off-label for NASH in non-diabetic patients. While it has shown some benefit for inflammation, it does not meaningfully improve fibrosis and carries long-term safety concerns (including a potential link to prostate cancer in men). Rezdiffra demonstrated improvement in both NASH resolution and fibrosis in clinical trials.

Rezdiffra vs. Semaglutide (Ozempic/Wegovy)

Semaglutide — the GLP-1 receptor agonist behind Ozempic and Wegovy — is being actively studied for MASH and has shown promising results for NASH resolution. However, as of 2026, Semaglutide is not FDA-approved for NASH/MASH. It also requires injection and works primarily through weight loss and metabolic pathways, rather than directly targeting liver THR-β like Rezdiffra.

Rezdiffra vs. Obeticholic Acid (Ocaliva)

Obeticholic Acid is an FXR agonist that was studied for NASH but did not receive FDA approval for this indication. It is approved for primary biliary cholangitis. Rezdiffra has a completely different mechanism and is currently the only FDA-approved treatment for NASH/MASH.

For a more detailed comparison of alternatives, see our post on alternatives to Rezdiffra.

Final Thoughts

Rezdiffra works by flipping a specific switch in your liver — the THR-β receptor — that tells it to burn fat, reduce inflammation, and slow scarring. Its selective design means it can do this without causing the heart and bone problems that older thyroid-based treatments caused.

If your doctor has prescribed Rezdiffra, understanding how it works can help you stay motivated during a treatment that takes months to show its full effect. Stay consistent, keep up with lab work, and talk to your doctor about any questions.

Ready to get started? Learn how to find a prescriber, or use Medfinder to check pharmacy availability near you.