2026-07-05 · resmetirom, Rezdiffra, MASH, MASLD, NASH, NAFLD, fatty liver, fibrosis, thyroid hormone receptor beta, hepatology · 20 min read

What is resmetirom and why is it a landmark FDA approval?

Resmetirom (brand name Rezdiffra) is a liver-selective thyroid hormone receptor beta (THR-beta) agonist made by Madrigal Pharmaceuticals. On 2024-03-14 the FDA granted accelerated approval under Subpart H for adults with metabolic dysfunction-associated steatohepatitis (MASH, previously called NASH) and moderate-to-advanced non-cirrhotic fibrosis (stages F2 or F3). It is the first drug the FDA has ever approved specifically for MASH. Two decades of trials — including obeticholic acid, which failed in 2020 and again in 2023 on the fibrosis endpoint (Sanyal 2021 Lancet REGENERATE analysis) — preceded this approval. The pivotal trial was Harrison 2024 MAESTRO-NASH (NEJM), which showed MASH resolution without fibrosis worsening in about 25.9 percent (80 mg) and 29.9 percent (100 mg) of patients at 52 weeks versus 9.7 percent on placebo, and fibrosis improvement of at least one stage in 24.2 percent and 25.9 percent versus 14.2 percent.

How much MASH resolution and fibrosis improvement should I expect?

In Harrison 2024 MAESTRO-NASH at 52 weeks, the absolute over-placebo improvement was about 15 to 20 percentage points on MASH resolution (roughly 26 to 30 percent on resmetirom versus 10 percent on placebo) and about 10 to 12 percentage points on fibrosis improvement (roughly 24 to 26 percent on resmetirom versus 14 percent on placebo). That means about one in four adults on resmetirom will see meaningful histologic improvement over a year — a real signal after decades of failed MASH trials, but far from a majority. The trial required biopsy-confirmed MASH with stage F1B, F2, or F3 fibrosis; benefit in adults outside that biopsy-defined phenotype is unproven. Confirmatory outcome data — whether the histologic improvement translates into fewer cases of cirrhosis, hepatocellular carcinoma, and liver-related death — will not be available until MAESTRO-NASH-OUTCOMES reads out around 2028.

Should I take 80 mg or 100 mg of resmetirom?

Body weight decides. The FDA label uses a 100 kg threshold: adults under 100 kg (about 220 lb) take 80 mg once daily, and adults at 100 kg or above take 100 mg once daily. Both doses were studied in MAESTRO-NASH and both are approved. The 100 mg arm showed slightly higher rates of MASH resolution and fibrosis improvement at 52 weeks, but the differences were modest and both doses beat placebo cleanly. Do not adjust the dose yourself. If you cross the 100 kg threshold in either direction on treatment, the change is a prescriber decision, not a self-titration.

Does resmetirom replace the 5 to 10 percent weight loss that reverses fatty liver?

No. This is the single most important thing to understand about the drug. Vilar-Gomez 2015 (Gastroenterology) established the dose-response between weight loss and MASH histology: roughly 5 to 7 percent body-weight loss resolves simple steatosis in most patients, and about 10 percent resolves MASH in around 64 percent and improves fibrosis in about 45 percent. Those numbers are as good as or better than resmetirom on paper, and they also improve cardiovascular risk, blood pressure, glycemic control, and lipid profile in ways the drug does not. In MAESTRO-NASH, the mean weight change on resmetirom was only about 3 kg — the drug works largely independent of weight. The correct framing is that resmetirom is additive on top of the 5 to 10 percent weight-loss foundation, not a substitute for it. If a patient loses the weight, resmetirom's job becomes closing the remaining fibrosis gap. If a patient does not lose the weight, resmetirom alone is doing much less than the combined package is capable of.

Can I take resmetirom with a GLP-1 like semaglutide or tirzepatide?

Yes, and the layered mechanism is one of the strongest reasons to consider it. Semaglutide in NASH (Newsome 2021, NEJM) produced MASH resolution in 59 percent of patients at 72 weeks but did not significantly improve fibrosis. Tirzepatide showed a similar dissociation in SYNERGY-NASH. Resmetirom addresses the fibrosis gap that GLP-1s do not consistently close. There is no clinically important pharmacokinetic interaction between resmetirom and semaglutide, tirzepatide, or other GLP-1 agonists, and the combination is common in practice for adults with obesity plus biopsy-confirmed F2 to F3 MASH. Watch for LFT changes at 4, 8, and 12 weeks after resmetirom initiation as with any patient. See our fatty liver and weight loss and GLP-1 medications compared guides for the fuller layering framework.

What are the statin interactions I need to know about?

Resmetirom raises exposure to certain statins that go through CYP3A4, so statin choice matters. Chalasani 2024 published practical guidance: pravastatin, rosuvastatin, and pitavastatin are preferred because they are not CYP3A4 substrates and interact minimally. Simvastatin is dose-limited on resmetirom (typically capped at 20 mg per day) because the interaction is more clinically important. Atorvastatin usually requires dose reduction depending on the starting dose. If you are on a statin when you start resmetirom, do not change your regimen without talking to your prescriber — the interaction is manageable in almost every case, but the choice of statin should be made deliberately.

How much does Rezdiffra cost in 2026 and will insurance cover it?

The list price at launch was about 47,400 US dollars per year (roughly 3,950 US dollars per month), placing resmetirom in the high-specialty tier alongside other novel hepatology drugs. Commercial insurance coverage consolidated through 2025 and 2026 with prior-authorization criteria typically including biopsy-confirmed MASH with F2 to F3 fibrosis, or a documented non-invasive fibrosis workup (VCTE, FIB-4, and ELF or similar). Medicaid coverage varies substantially by state. Medicare Part D coverage requires meeting the same clinical criteria and is typically subject to a specialty-tier copay. Madrigal Pharmaceuticals operates a patient-assistance program that reduces or eliminates out-of-pocket cost for eligible commercially insured or uninsured adults. Discuss the specific coverage pathway with the prescribing hepatologist or an obesity-medicine or endocrinology clinic that has staff experienced with the Rezdiffra prior authorization.

Is resmetirom approved for compensated cirrhosis (stage F4)?

No. MAESTRO-NASH excluded adults with cirrhosis and the FDA label explicitly restricts use to non-cirrhotic MASH with stage F1B, F2, or F3 fibrosis. Compensated cirrhosis (F4 without decompensation) was not tested and off-label use is not recommended outside a clinical trial. Decompensated cirrhosis — a history of ascites, variceal bleeding, hepatic encephalopathy, or jaundice from liver dysfunction — is a categorical exclusion. Screening for cirrhosis before starting resmetirom is standard: transient elastography (VCTE) with liver stiffness measurement, FIB-4 score, and where indicated a formal ELF or magnetic resonance elastography, plus imaging to rule out portal-hypertension features. Anyone with cirrhosis should be under a hepatologist, and the treatment conversation there is about cirrhosis management, not resmetirom.

What is the FDA Subpart H accelerated approval and why does it matter?

Resmetirom was approved under Subpart H, the FDA's accelerated approval pathway for serious conditions where a surrogate endpoint (in this case histology — MASH resolution and fibrosis improvement) is reasonably likely to predict clinical benefit (cirrhosis, hepatocellular carcinoma, liver-related death, liver transplant, all-cause mortality). Confirmatory clinical outcome data are due from MAESTRO-NASH-OUTCOMES, projected to read out around 2028. If the confirmatory trial fails to show a clinical outcome benefit, the FDA can withdraw approval. This is the same regulatory pathway used for many oncology drugs. Practically, the drug is fully available and fully insured under normal criteria in 2026, but the honest framing includes that we do not yet know the hard-outcome benefit.

Resmetirom (Rezdiffra) for MASH: What the First FDA-Approved Fatty Liver Drug Means for Weight and Fibrosis

Resmetirom (brand name Rezdiffra) is the first medication the FDA has ever approved specifically for metabolic dysfunction-associated steatohepatitis (MASH) — the inflammatory stage of the disease previously called NASH, and the stage that can progress to fibrosis and cirrhosis. Approval came on 2024-03-14 under FDA Subpart H accelerated approval, based on Harrison 2024 MAESTRO-NASH (New England Journal of Medicine), the pivotal 966-adult phase 3 trial in biopsy-confirmed MASH with stage F1B, F2, or F3 fibrosis. At 52 weeks, MASH resolution without fibrosis worsening occurred in 25.9 percent (80 mg) and 29.9 percent (100 mg) of resmetirom-treated adults versus 9.7 percent on placebo, and fibrosis improvement of at least one stage occurred in 24.2 percent and 25.9 percent versus 14.2 percent on placebo. Roughly one in four adults on resmetirom saw meaningful histologic improvement over a year — a real signal after two decades of failed MASH trials, but far from a majority.

The honest framing: resmetirom is a milestone, not a cure. It produces about 15 to 20 percentage points of absolute MASH resolution over placebo and about 10 to 12 percentage points of absolute fibrosis improvement at 52 weeks. It is approved on histologic surrogate endpoints under FDA Subpart H — the confirmatory MAESTRO-NASH-OUTCOMES clinical outcome trial is not due to read out until roughly 2028. Mean weight change on the drug was only about 3 kg, so resmetirom is not a weight-loss drug and does not replace the 5 to 10 percent body-weight loss that resolves steatosis in the majority of patients (Vilar-Gomez 2015, Gastroenterology) — it is additive on top of the lifestyle foundation, not a substitute for it. At a launch list price of roughly US$47,400 per year, insurance coverage and prior authorization are the practical bottleneck for many patients. This guide covers who qualifies under the FDA label, how the drug works, dose and monitoring, how it compares with GLP-1 therapy and bariatric surgery, statin drug-drug interactions, and the red flags that warrant same-day evaluation.

Quick stats

• MAESTRO-NASH MASH resolution at 52 weeks: 25.9% (80 mg) and 29.9% (100 mg) vs 9.7% placebo (Harrison 2024, NEJM).
• MAESTRO-NASH fibrosis improvement at 52 weeks (≥ 1 stage): 24.2% (80 mg) and 25.9% (100 mg) vs 14.2% placebo.
• FDA accelerated approval date: 2024-03-14, under Subpart H; confirmatory MAESTRO-NASH-OUTCOMES due ~2028.
• US MASLD prevalence: ~30% of adults; MASH ~5%; ~20% of MASH progresses to cirrhosis over 10 to 15 years (Younossi 2019, Hepatology).
• Foundation still required: 5 to 10% body-weight loss remains the primary lever for MASH histology (Vilar-Gomez 2015, Gastroenterology).
• List price: ~US$47,400/year at launch; commercial coverage consolidating in 2026; Medicaid variability by state.
• 911 red flag: new jaundice with abdominal pain, confusion, or bleeding — evaluate for drug-induced liver injury or hepatic decompensation.

Who qualifies for resmetirom under the FDA label

The FDA label is narrow, and honest patient framing starts with whether a specific person is inside or outside it. Resmetirom is approved for adults with non-cirrhotic MASH and moderate-to-advanced fibrosis (stage F1B, F2, or F3). It is not approved for MASLD without significant fibrosis, and it is categorically not approved for cirrhosis.

The AASLD 2024 practice guidance update (Hepatology) formalized the noninvasive diagnostic pathway used in most US practices in 2026: VCTE (transient elastography) with a liver stiffness measurement in the 8 to 15 kPa range, plus a FIB-4 score above 1.3 or an ELF (enhanced liver fibrosis) score above 9.8, is now considered acceptable evidence of F2 or F3 fibrosis in many clinical settings — biopsy remains the gold standard but is no longer required for prescribing in most workflows. See our fatty liver and weight loss guide for the fuller diagnostic pathway.

How resmetirom works

Four mechanistic threads describe how resmetirom improves MASH histology, and one describes what the drug is not.

1. Liver-selective THR-beta agonism

Sinha 2018 (Nature Reviews Endocrinology) and Kokkorakis 2024 (Nature Reviews Endocrinology) describe the primary mechanism. Resmetirom is a liver-selective thyroid hormone receptor beta (THR-beta) agonist. THR-beta is the dominant thyroid receptor isoform in liver cells; activating it increases hepatic mitochondrial fatty-acid oxidation, boosts LDL clearance through upregulated LDL-receptor expression, and reduces de novo lipogenesis. Because the drug preferentially targets THR-beta and is concentrated in the liver, it produces minimal cardiac (THR-alpha) or skeletal effects — the safety profile does not include the tachycardia, atrial fibrillation, or bone-loss signals of systemic thyroid hormone excess.

2. Independent of weight loss

Harrison 2024 documented that mean weight change on resmetirom in MAESTRO-NASH was only about 3 kg, and the histologic improvement occurred with or without meaningful weight change. This mechanistically distinguishes resmetirom from GLP-1 receptor agonists, where most of the hepatic benefit tracks with the weight loss the drugs produce (Wilding 2021 STEP-1 sub-analysis; Newsome 2021, NEJM). Resmetirom’s histologic effect is a direct hepatic effect, not a weight-mediated one.

3. Additive to weight loss and GLP-1 therapy

There is no clinically important pharmacokinetic interaction between resmetirom and semaglutide or tirzepatide, and the mechanisms are complementary — GLP-1s reduce hepatic steatosis largely through weight loss and modest direct hepatic effects; resmetirom addresses fibrosis directly. The layered combination is common in practice for adults with obesity plus biopsy-confirmed F2 to F3 MASH. Newsome 2021 semaglutide in NASH showed MASH resolution of 59 percent at 72 weeks but no significant fibrosis improvement; adding resmetirom addresses that gap.

4. What resmetirom is not

Resmetirom is not a cirrhosis drug — F4 was excluded from MAESTRO-NASH and the FDA label. It is not a weight-loss drug — the mean weight change of about 3 kg is far below what a GLP-1 or bariatric surgery delivers. It is not appropriate for MASLD without significant fibrosis — F0 and F1A patients are outside the trial-tested and label-approved population. And it is not a substitute for the 5 to 10 percent weight-loss foundation — Vilar-Gomez 2015 showed lifestyle-driven weight loss produces MASH resolution rates that meet or exceed the drug’s effect size while also improving cardiovascular risk. Resmetirom is additive.

Dose and monitoring

Dose is decided by body weight at initiation. The 100 kg (about 220 lb) threshold in the FDA label separates the two available doses.

The FDA 2024-06 post-marketing requirements flagged drug-induced liver injury (DILI) monitoring and statin drug-drug interactions as the two most important safety programs on the drug. The LFT monitoring pattern above is the practical implementation.

Time-course and outcomes

The resmetirom histologic effect builds over the first 52 weeks and appears to hold or extend with continued therapy. Confirmatory hard-outcome data from MAESTRO-NASH-OUTCOMES is due around 2028.

5-step protocol for resmetirom therapy

This is the practical clinical rhythm most hepatologists and obesity-medicine prescribers use in 2026 for a candidate patient.

Step 1: Confirm MASH with F1B, F2, or F3 fibrosis

Biopsy is the historical gold standard, but the AASLD 2024 practice guidance update and Rinella 2024 (Hepatology) support the noninvasive workup — VCTE liver stiffness measurement 8 to 15 kPa plus FIB-4 > 1.3 or ELF > 9.8 — as acceptable evidence in most US practices. Steatosis alone (MASLD without significant fibrosis) is not an indication; F4 cirrhosis is an exclusion.

Step 2: Screen exclusions

The main exclusions are decompensated cirrhosis (categorical contraindication), F4 compensated cirrhosis (off-label, not recommended outside a study), pregnancy (teratogenicity data limited), and potent CYP3A4 inhibitors without adjustment. Review the complete medication list — statins, azole antifungals, macrolide antibiotics, and grapefruit juice are the most common practical concerns.

Step 3: Baseline labs and statin review

Order a comprehensive LFT panel (AST, ALT, alkaline phosphatase, total bilirubin), a lipid panel, a TSH to rule out primary thyroid dysfunction as a competing explanation for hepatic biomarker changes, a pregnancy test in women of childbearing potential, and a review of the current statin regimen per Chalasani 2024. Pravastatin, rosuvastatin, and pitavastatin are the preferred statin partners; simvastatin is dose-limited; atorvastatin often requires dose reduction.

Step 4: Dose by body weight and titrate LFT monitoring

Under 100 kg receives 80 mg once daily; 100 kg or above receives 100 mg once daily. Monitor LFTs at 4, 8, and 12 weeks, then quarterly for the first year, then every 6 months if stable. Hold the drug for ALT above 5 times upper limit of normal, any new bilirubin elevation, or any clinical hepatic-injury symptom.

Step 5: Reassess at 52 weeks

At the one-year mark, repeat VCTE and FIB-4 as noninvasive fibrosis tracking, and consider a repeat biopsy in selected cases where the noninvasive picture is ambiguous or where continued therapy is being reconsidered. The clinical decision is whether the histologic and biomarker signals justify continuation, and confirmatory outcome data will accumulate through 2028 to inform the longer decision.

What resmetirom actually does — compared to alternatives

The honest comparison table places resmetirom next to the therapies with the strongest MASH histology data.

The single most important row is lifestyle 5 to 10% weight loss. When achieved, it matches or exceeds resmetirom on histology and delivers the cardiovascular, blood-pressure, glycemic, and lipid benefits the drug does not. Resmetirom’s honest role is closing the fibrosis gap that GLP-1s do not consistently close, and providing a histologic option for adults who cannot or do not lose enough weight.

MASH with type 2 diabetes

Coexisting type 2 diabetes roughly doubles the rate of fibrosis progression compared with MASLD alone, and it is the most common comorbidity in MAESTRO-NASH candidates. Layer resmetirom on top of the standard T2D framework rather than as a substitute: metformin as an anchor, a GLP-1 receptor agonist as the weight and glycemic driver, and an SGLT2 inhibitor where cardiovascular or renal indications support it. See our diabetes and weight loss, metformin and weight, and SGLT2 inhibitors and weight guides for the layered logic. Resmetirom’s mechanism is complementary — hepatic direct effect on top of the metabolic and weight-mediated improvements the T2D regimen already produces.

MASH with obesity on a GLP-1 receptor agonist

This is the population that benefits most obviously from adding resmetirom. Newsome 2021 semaglutide in NASH resolved MASH in 59 percent at 72 weeks but did not significantly improve fibrosis; SYNERGY-NASH showed a similar signal with tirzepatide. If the GLP-1 has produced substantial weight loss and improved steatosis but the fibrosis stage on repeat noninvasive workup has not changed, resmetirom is a reasonable second addition. Watch LFTs at 4, 8, and 12 weeks after resmetirom initiation as with any patient; no dose adjustment of the GLP-1 is needed. See our Wegovy weight loss and Zepbound weight loss guides for the GLP-1-specific management.

MASH in the “lean MASH” phenotype

About 10 to 20 percent of MASLD occurs in adults with normal or near-normal BMI. The mechanism is similar to obesity-associated MASLD — insulin resistance and visceral adiposity disproportionate to weight — but the therapeutic conversation changes because there is less weight to lose. Genetic variants (PNPLA3, TM6SF2) are more common in this phenotype. When lean-phenotype adults meet the biopsy or noninvasive fibrosis criteria for F1B, F2, or F3 MASH, resmetirom is a legitimate primary pharmacologic option — the weight-loss lever that dominates the intervention conversation in most MASH patients is smaller here, and a direct hepatic-effect drug fits the biology.

Compensated cirrhosis (F4) — off-label and not recommended

MAESTRO-NASH excluded F4 compensated cirrhosis, and the FDA label restricts use to non-cirrhotic F1B through F3. Off-label use in compensated cirrhosis has been discussed in hepatology forums but is not supported by controlled data, and the safety of the drug in a fibrotic-plus-cirrhotic phenotype has not been established. Decompensated cirrhosis is a categorical contraindication. Anyone with cirrhosis should be under a hepatologist, and the treatment discussion there is about portal hypertension, HCC surveillance, transplant candidacy, and the broader cirrhosis-management framework — not resmetirom initiation. See our fatty liver and weight loss guide for the cirrhosis red-flag list and referral thresholds.

Statin co-management on resmetirom

Statin choice is the most common practical drug-drug interaction question. Chalasani 2024 published the practical guidance most prescribers now use.

• Pravastatin, rosuvastatin, pitavastatin — preferred; not CYP3A4 substrates; interact minimally with resmetirom.
• Simvastatin — dose-limited; typically capped at 20 mg per day on resmetirom.
• Atorvastatin — dose reduction consideration; the interaction is clinically important at higher doses.
• Lovastatin — avoid the combination where possible.

Do not switch statins yourself. If you are on a statin when you start resmetirom, the switch is a prescriber decision with a recent lipid panel and LFT panel in hand. See our statins and weight guide for the fuller statin framework.

Cost and insurance coverage in 2026

The launch list price was approximately US$47,400 per year (about US$3,950 per month), placing Rezdiffra in the high-specialty tier. Commercial insurance coverage has consolidated through 2025 and 2026 with prior-authorization criteria that typically require biopsy-confirmed MASH with F2 or F3 fibrosis, or a documented noninvasive workup (VCTE, FIB-4, and ELF or similar). Medicaid coverage varies substantially by state. Medicare Part D coverage requires meeting the same clinical criteria and is typically subject to a specialty-tier copay. Madrigal Pharmaceuticals operates a patient-assistance program that reduces or eliminates out-of-pocket cost for eligible commercially insured or uninsured adults. Practically, the coverage pathway is worth working through with a hepatologist or obesity-medicine clinic that has staff experienced with the Rezdiffra prior-authorization process — the first pass often needs supporting documentation.

The MASH pipeline that follows resmetirom

Resmetirom is the first FDA-approved MASH drug, not the last. Ratziu 2024 summarized the near-term pipeline: pegozafermin (FGF-21 analogue) and efruxifermin (another FGF-21 analogue) are in phase 3 with signal on both MASH resolution and fibrosis improvement; tirzepatide in SYNERGY-NASH showed both MASH and preliminary fibrosis benefit; pemvidutide is a dual GLP-1/glucagon agonist in phase 2 and 3 trials. Several combination trials are testing resmetirom plus a GLP-1 or plus an FGF-21 analogue. The likely 2028 landscape includes several approved MASH agents with different mechanisms, and combination therapy will be a live clinical question. Resmetirom’s first-mover position gives it a durable role, especially for the non-cirrhotic F1B through F3 phenotype where it has trial-level data.

Red flags — when to call your doctor

These findings warrant same-week or same-day evaluation rather than waiting for routine follow-up.

• New jaundice with abdominal pain, confusion, or bleeding — evaluate for drug-induced liver injury (DILI) or hepatic decompensation; 911 if confusion, altered mental status, or bleeding is present.
• Persistent ALT above 5 times upper limit of normal — hold resmetirom; call the prescribing hepatologist; do not self-discontinue without a plan.
• Severe diarrhea with dehydration — GI intolerance is common in the first 12 weeks; hold and hydrate; call the prescriber if not improving.
• New gallstone symptoms (right upper quadrant pain, nausea, fever) — the combination of weight loss, statin, and resmetirom may modestly increase gallstone risk; call for imaging and evaluation.
• Pregnancy or unplanned conception — stop resmetirom immediately; teratogenicity data are limited; contact the prescribing clinician.
• Accidental over-ingestion in a child or adult — call 1-800-222-1222 (US Poison Control) for immediate guidance.

Bottom line

Resmetirom is a genuine milestone. After two decades of failed MASH trials — including obeticholic acid, which failed FDA approval on the fibrosis endpoint (Sanyal 2021 REGENERATE analysis, Lancet) — the FDA has approved the first drug specifically for MASH. In MAESTRO-NASH at 52 weeks, resmetirom produced MASH resolution in roughly one in four patients and fibrosis improvement in roughly one in four, both about 10 to 20 percentage points over placebo (Harrison 2024, NEJM). The drug is approved for non-cirrhotic MASH with F1B through F3 fibrosis under FDA Subpart H accelerated approval; confirmatory hard-outcome data from MAESTRO-NASH-OUTCOMES are due around 2028. It is expensive, requires prior authorization in most insurance settings, and does not replace the 5 to 10 percent body-weight loss that resolves steatosis in the majority of patients (Vilar-Gomez 2015, Gastroenterology). The correct framing is additive: keep the weight-loss foundation and the GLP-1 or SGLT2 layering where indicated, and add resmetirom to close the fibrosis gap in the biopsy or noninvasively confirmed F1B through F3 population.

How this connects to the rest of the site

For the lifestyle and diagnostic context, start with fatty liver and weight loss, metabolic syndrome and weight loss, insulin resistance and weight loss, and visceral fat. For the T2D and drug-class layering, see diabetes and weight loss, metformin and weight, SGLT2 inhibitors and weight, and statins and weight. For the GLP-1 comparisons that are usually the parallel conversation, see Wegovy weight loss, Zepbound weight loss, semaglutide weight loss, and tirzepatide weight loss. For the surgical option that produces the largest histologic reversal, see gastric bypass surgery and sleeve gastrectomy. For the broader safety framing across the modern obesity pharmacopoeia, see weight loss drug safety.

Resmetirom and MASH FAQ

What is resmetirom and why is it a landmark FDA approval? It is a liver-selective THR-beta agonist approved 2024-03-14 as the first drug specifically for MASH, based on Harrison 2024 MAESTRO-NASH (NEJM).

How much MASH resolution and fibrosis improvement should I expect? At 52 weeks, MASH resolution in 26 to 30 percent (vs 10 percent placebo) and fibrosis improvement in 24 to 26 percent (vs 14 percent) — about 15 to 20 and 10 to 12 percentage points over placebo.

Should I take 80 mg or 100 mg? Body weight decides — under 100 kg takes 80 mg daily; 100 kg or above takes 100 mg daily.

Does resmetirom replace the 5 to 10 percent weight loss that reverses fatty liver? No. Vilar-Gomez 2015 showed lifestyle-driven weight loss produces MASH histology numbers as good as the drug and improves cardiovascular risk in ways the drug does not. Resmetirom is additive.

Can I take it with a GLP-1? Yes — layered therapy is common; the mechanisms are complementary; no clinically important pharmacokinetic interaction.

What are the statin interactions? Pravastatin, rosuvastatin, and pitavastatin are preferred; simvastatin is dose-limited; atorvastatin often requires dose reduction (Chalasani 2024).

How much does it cost in 2026? List price roughly US$47,400 per year; commercial coverage consolidating; Madrigal patient-assistance program available.

Is it approved for cirrhosis? No — non-cirrhotic F1B, F2, or F3 fibrosis only; F4 was excluded from MAESTRO-NASH and is not recommended outside a study.

What is FDA Subpart H accelerated approval? Approval on a surrogate endpoint (histology) reasonably likely to predict clinical benefit; confirmatory MAESTRO-NASH-OUTCOMES clinical outcome data due around 2028.