Rezdiffra
Resmetirom – First-in-Class Thyroid Hormone Receptor Beta (THR-β) Agonist for MASH
Quick Facts About Rezdiffra
Key Takeaways About Rezdiffra
- First-ever MASH therapy: Rezdiffra (resmetirom) received accelerated FDA approval on 14 March 2024 as the first medicine specifically indicated for non-cirrhotic MASH with moderate to advanced fibrosis (stages F2–F3)
- Liver-targeted thyroid receptor activation: Resmetirom selectively activates thyroid hormone receptor beta (THR-β) in hepatocytes, increasing fat oxidation and reducing liver fat, inflammation, and fibrosis while largely sparing the cardiac and bone effects of classic thyroid hormones
- Weight-based once-daily dosing: Take 80 mg once daily if you weigh less than 100 kg (220 lb), and 100 mg once daily if you weigh 100 kg or more. A 60 mg strength is available for dose modification
- Adjunct to lifestyle therapy, not a replacement: Rezdiffra must be used together with a healthy diet, physical activity, and treatment of related conditions such as obesity, type 2 diabetes, hypertension, and dyslipidaemia
- Careful monitoring required: Liver function tests should be checked before starting and at regular intervals during treatment. Rezdiffra interacts with many statins and CYP2C8 inhibitors and must not be used with gemfibrozil or in decompensated cirrhosis
What Is Rezdiffra and What Is It Used For?
Rezdiffra is the brand name of resmetirom, a liver-directed, oral, selective thyroid hormone receptor beta (THR-β) agonist. It is approved for use together with diet and exercise to treat adults with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) who have moderate to advanced liver fibrosis, corresponding to histological stages F2 to F3. It is the first and only drug therapy developed specifically for MASH.
Metabolic dysfunction-associated steatohepatitis (MASH), formerly called non-alcoholic steatohepatitis (NASH), is the progressive and inflammatory form of metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD). MASH is characterised by excess fat accumulation in the liver (hepatic steatosis), cellular damage (hepatocyte ballooning), lobular inflammation, and progressive scarring (fibrosis). If left untreated in patients with advanced fibrosis, MASH can progress to cirrhosis, liver failure, hepatocellular carcinoma, and the need for liver transplantation. MASLD is estimated to affect around 30% of adults worldwide, and MASH affects approximately 5%, making it one of the leading causes of chronic liver disease globally.
Until the approval of Rezdiffra, there was no medicine approved specifically for MASH. Management relied on weight loss, dietary change, physical activity, and treatment of coexisting conditions such as obesity, type 2 diabetes, and dyslipidaemia. While these interventions remain central to MASH care, they are often insufficient on their own, and many patients continue to progress to advanced fibrosis and cirrhosis. The approval of Rezdiffra therefore represents a landmark in hepatology.
Rezdiffra belongs to a novel drug class called thyroid hormone receptor beta (THR-β) selective agonists. Thyroid hormones have potent effects on lipid metabolism in the liver, but classical thyroid hormones (such as levothyroxine) also activate the alpha subtype of the thyroid hormone receptor, which is expressed in the heart, bone, and brain – leading to unwanted effects such as tachycardia, bone loss, and heat intolerance. Resmetirom was designed specifically to activate THR-β, the dominant thyroid receptor subtype in the liver, while having minimal activity at the cardiac and skeletal THR-α subtype. The result is a drug that harnesses the lipid-lowering and anti-steatotic benefits of thyroid hormone signalling within the liver without the systemic thyrotoxic effects.
The approved indication limits Rezdiffra to adults with non-cirrhotic MASH (i.e. fibrosis stages F2 or F3 on the METAVIR or equivalent scale). It should not be used in patients with decompensated cirrhosis (Child-Pugh B or C), and its use in compensated cirrhosis (F4) is not recommended because clinical benefit has not been established and there are concerns about risk in advanced liver disease. It is meant to be added to – not substituted for – appropriate management of obesity, diabetes, and dyslipidaemia.
Rezdiffra was granted accelerated approval by the US Food and Drug Administration (FDA) in March 2024, based on improvements in surrogate histological endpoints (MASH resolution and fibrosis improvement) at 52 weeks of the phase 3 MAESTRO-NASH trial. Continued approval is contingent on verification of clinical benefit in ongoing outcome studies demonstrating reductions in progression to cirrhosis, liver decompensation, liver transplantation, and liver-related death. Regulatory review is also ongoing in Europe, the United Kingdom, and other jurisdictions.
What Should You Know Before Taking Rezdiffra?
Before starting Rezdiffra, your doctor will review your medical history, perform blood tests (including liver function tests, thyroid function, and a lipid panel), and confirm the stage of liver fibrosis. Tell your doctor about all medicines, supplements, and herbal products you take – Rezdiffra has many drug interactions, particularly with statins, gemfibrozil, and CYP3A4 or OATP1B1 substrates.
Contraindications
You must not take Rezdiffra if any of the following apply:
- Decompensated cirrhosis – Rezdiffra is contraindicated in patients with decompensated hepatic impairment (Child-Pugh class B or C), because these patients were excluded from clinical trials and the safety and efficacy have not been established. Signs of decompensation include ascites, encephalopathy, variceal bleeding, or jaundice due to liver failure
- Concomitant use of strong CYP2C8 inhibitors – particularly gemfibrozil (a fibrate) and clopidogrel (an antiplatelet). Co-administration substantially increases resmetirom plasma concentrations and the risk of drug-induced liver injury and other adverse effects
- Known hypersensitivity to resmetirom or any of the tablet’s excipients
Warnings and Precautions
Rezdiffra can cause drug-induced liver injury, including elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. In rare cases liver enzyme elevations have been severe. Your doctor will check liver function tests before starting treatment, after the first 3 months, and periodically thereafter. Contact your doctor promptly if you develop yellowing of the skin or eyes (jaundice), dark urine, pale stools, unexplained nausea, right upper abdominal pain, or fatigue that cannot otherwise be explained.
Discuss the following with your doctor before and during Rezdiffra treatment:
- Existing liver disease – especially cirrhosis, portal hypertension, or any prior episode of liver decompensation. Rezdiffra should not be started in decompensated cirrhosis and should be used cautiously if there is any evidence of portal hypertension
- Thyroid disease or abnormal thyroid function – resmetirom may transiently lower free thyroxine (T4) through its pharmacological action. Clinically meaningful thyroid dysfunction has been uncommon in clinical trials, but thyroid function should be assessed before starting, and patients on thyroid hormone replacement (such as levothyroxine) may need dose adjustment
- Gallbladder disease (cholelithiasis/cholecystitis) – a small increase in gallbladder-related events has been observed with resmetirom. Tell your doctor if you experience sudden severe pain in the upper right side of the abdomen, especially after eating fatty foods
- Chronic kidney disease – no dose adjustment is generally required, but close monitoring is advised in advanced renal impairment
- Current or planned pregnancy – reliable contraception is recommended because data on human pregnancy are limited (see Pregnancy and Breastfeeding below)
- Statin therapy – Rezdiffra raises plasma concentrations of many statins through OATP1B1 and CYP3A4 interactions; your doctor will review your lipid-lowering regimen and may reduce the statin dose or change statin
- Use of other medicines – including over-the-counter products, herbal supplements, and vitamins, because Rezdiffra has extensive drug interactions
Monitoring During Treatment
Because Rezdiffra is a new medicine, and because MASH itself is a progressive liver disease with metabolic comorbidities, ongoing monitoring is an integral part of treatment. Typical monitoring includes:
- Liver function tests (ALT, AST, bilirubin, alkaline phosphatase) before starting, at month 3, and at least every 6 months thereafter – with additional testing at any sign of liver injury
- Lipid panel before and during treatment; resmetirom often reduces low-density lipoprotein (LDL) cholesterol, apolipoprotein B, and triglycerides, and lipid-modifying therapy may need dose adjustment
- Thyroid function tests (TSH, free T4) at baseline and periodically
- Non-invasive assessment of liver fibrosis and steatosis (FibroScan®/VCTE, FIB-4, MR-PDFF or MRE) to evaluate response
- Blood pressure, weight, glycaemic control, and cardiovascular risk factors, as MASH is a systemic metabolic disease
Pregnancy and Breastfeeding
The safety of Rezdiffra during pregnancy has not been established in humans. Animal studies have shown some effects on fetal development at high doses. Women of childbearing potential should use effective contraception during treatment and should discuss Rezdiffra with their doctor before planning pregnancy. If you become pregnant while taking Rezdiffra, tell your doctor promptly so that the benefits and risks can be reviewed.
It is not known whether resmetirom is excreted in human milk, or the effects on the breastfed infant or on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions, breastfeeding is generally not recommended while taking Rezdiffra. Your doctor can help you weigh the importance of breastfeeding against the expected benefits of Rezdiffra.
Driving and Operating Machinery
Rezdiffra has not been specifically studied for effects on driving. Dizziness has been reported and, if this occurs, you should not drive or use machines until the symptoms resolve.
Alcohol and Diet
Alcohol intake accelerates MASH and any liver disease and can increase the risk of drug-induced liver injury. Patients taking Rezdiffra should limit alcohol intake, and complete abstinence is often recommended. A Mediterranean-style diet, regular physical activity, and weight loss remain cornerstone interventions and should continue throughout treatment.
How Does Rezdiffra Interact with Other Drugs?
Resmetirom is metabolised by CYP2C8 and CYP3A4 and is a substrate and inhibitor of the hepatic transporter OATP1B1. As a result it has extensive interactions with statins, fibrates, antiplatelet drugs, azole antifungals, rifampin, and cyclosporine. Some combinations are absolutely contraindicated (such as gemfibrozil) while others require dose adjustment or extra monitoring.
Drug-drug interactions with Rezdiffra arise through two main mechanisms. First, resmetirom is primarily metabolised by the cytochrome P450 enzymes CYP2C8 and CYP3A4, so inhibitors of these enzymes can increase resmetirom exposure (risk of toxicity) while inducers can reduce exposure (risk of treatment failure). Second, resmetirom inhibits the organic anion-transporting polypeptide 1B1 (OATP1B1), which is responsible for hepatic uptake of several drugs – most notably statins – increasing their plasma concentrations and the risk of adverse events such as myopathy.
Contraindicated Combinations
The following medicines must not be taken together with Rezdiffra:
| Medicine | Therapeutic Area | Reason for Contraindication |
|---|---|---|
| Gemfibrozil | Lipid-lowering (fibrate) | Strong CYP2C8 inhibitor; substantially raises resmetirom exposure and risk of hepatotoxicity |
| Clopidogrel | Antiplatelet | Strong CYP2C8 inhibitor; markedly increases resmetirom levels. An alternative antiplatelet (e.g. prasugrel or ticagrelor) should be considered |
| Simvastatin (>20 mg/day) and rosuvastatin (>20 mg/day) | Lipid-lowering (statins) | High-dose co-administration markedly increases statin exposure and the risk of myopathy and rhabdomyolysis. Dose limits apply; in some cases the combination is avoided altogether |
Major Interactions Requiring Dose Adjustment
| Medicine / Drug Class | Mechanism | Recommendation |
|---|---|---|
| Pravastatin, pitavastatin, rosuvastatin, atorvastatin, simvastatin | OATP1B1 and/or CYP3A4 – raises statin concentrations | Limit statin dose; review by prescriber; monitor for muscle pain, weakness, dark urine |
| Itraconazole, ketoconazole, posaconazole, voriconazole | Strong CYP3A4 inhibitors | Avoid co-administration or reduce Rezdiffra dose as advised in prescribing information |
| Clarithromycin, erythromycin | Moderate-to-strong CYP3A4 inhibition | Use with caution; consider azithromycin as an alternative |
| Rifampin, phenytoin, carbamazepine, phenobarbital | Strong CYP3A4 inducers | May reduce resmetirom efficacy; avoid co-administration |
| Cyclosporine | OATP1B1 inhibition; multi-transporter interaction | Avoid concomitant use where possible; specialist supervision required |
| St. John’s wort (Hypericum perforatum) | CYP3A4 inducer | Avoid. Reduces Rezdiffra plasma levels and efficacy |
| Levothyroxine and other thyroid hormone replacement | Pharmacodynamic – both act on thyroid hormone signalling | Monitor TSH and free T4; adjust levothyroxine dose if required |
| Oral contraceptives | Potential CYP3A4-mediated interaction | Monitor for breakthrough bleeding; additional non-hormonal contraception may be advised |
| Warfarin and direct oral anticoagulants | Potential CYP-mediated interaction | Monitor INR or anticoagulant activity; dose adjustment may be needed |
Minor Interactions and Everyday Considerations
- Proton pump inhibitors (omeprazole, esomeprazole) – no clinically important interaction expected, but liver function should continue to be monitored as with all patients on Rezdiffra
- Metformin, GLP-1 receptor agonists (semaglutide, liraglutide, tirzepatide) – often co-prescribed for type 2 diabetes or obesity in MASH; no clinically relevant pharmacokinetic interaction with Rezdiffra, and combinations are frequently used in clinical practice
- Fish oil and omega-3 supplements – no known interaction
- Grapefruit and grapefruit juice – contain furanocoumarins that inhibit intestinal CYP3A4; large amounts are best avoided, as is common advice with other CYP3A4 substrates
- Vitamin E (high-dose α-tocopherol) – sometimes used in non-diabetic MASH; no major pharmacokinetic interaction, but combined use should be guided by your hepatologist
The interactions listed above are representative but not exhaustive. Always keep an up-to-date list of all medicines, supplements, and herbal products you take, and share it with your doctor and pharmacist before starting Rezdiffra or any new drug.
What Is the Correct Dosage of Rezdiffra?
Rezdiffra is taken orally once daily, with or without food, at about the same time each day. The standard adult dose is 80 mg once daily for patients weighing less than 100 kg (220 lb) and 100 mg once daily for patients weighing 100 kg or more. A 60 mg strength is available for dose modification in specific clinical situations. Always take Rezdiffra exactly as prescribed and do not stop without speaking to your doctor.
Adults
Standard Weight-Based Dosing
Less than 100 kg (<220 lb): 80 mg once daily.
100 kg or more (≥220 lb): 100 mg once daily.
Swallow the tablet whole with water. Rezdiffra may be taken with or without food, and may be taken at any time of day that best supports adherence. Doses should be taken at approximately the same time each day.
Dose Modification with 60 mg Tablets
A 60 mg tablet strength is available. It may be used when a prescriber decides to reduce the dose in response to side effects, significant drug interactions (for example co-administration with moderate CYP3A4 inhibitors), or laboratory abnormalities. Dose modification should always be directed by the prescribing physician.
Children and Adolescents
Not Recommended Under 18 Years
The safety and efficacy of Rezdiffra have not been established in children or adolescents under 18 years of age. It is not currently approved for paediatric use. Management of paediatric MASLD/MASH should focus on weight management, diet, and exercise under the care of a paediatric hepatologist.
Elderly Patients (65 years and older)
Same Weight-Based Dosing
No dose adjustment is required for older adults based on age alone. Dosing follows the same weight-based recommendations as for younger adults. However, older patients are more likely to have impaired hepatic or renal function, concomitant medications, and comorbid conditions, and should therefore be monitored more closely – especially for drug interactions with statins and anticoagulants.
Patients with Liver Impairment
Compensated vs Decompensated Cirrhosis
Rezdiffra is not recommended in patients with compensated cirrhosis (Child-Pugh A) outside of the narrow indication, because clinical benefit in F4 fibrosis has not been established. It is contraindicated in decompensated cirrhosis (Child-Pugh B or C) where systemic exposure is expected to be much higher and the risk of serious adverse effects is unacceptably increased. In mild-to-moderate hepatic impairment without cirrhosis, the standard dosing applies, with close monitoring.
Patients with Kidney Impairment
No Routine Dose Adjustment
No dose adjustment is generally recommended in mild to moderate renal impairment. Data in severe renal impairment and end-stage renal disease are limited, and Rezdiffra should be used with caution and close monitoring in these patients.
Missed Dose
If you miss a dose of Rezdiffra:
- Take it as soon as you remember on the same day, unless it is close to the time of your next scheduled dose
- If it is almost time for your next dose, skip the missed dose and continue with your regular schedule
- Never take two doses to make up for a missed one
Overdose
Experience with resmetirom overdose in humans is limited. In case of accidental overdose, contact your local poison control centre or go to the nearest emergency department. There is no specific antidote. Treatment is supportive and guided by clinical and laboratory findings, including monitoring of liver and thyroid function. Hemodialysis is unlikely to be effective because resmetirom is highly protein-bound.
MASH is a chronic, progressive disease. Stopping Rezdiffra can lead to return of hepatic steatosis and loss of the reduction in fibrosis that was achieved during treatment. Any change in therapy should be discussed with your hepatologist, because the underlying metabolic condition requires ongoing management even if Rezdiffra is discontinued.
What Are the Side Effects of Rezdiffra?
Like all medicines, Rezdiffra can cause side effects, though not every patient experiences them. The most common are gastrointestinal – diarrhoea and nausea – usually mild to moderate and often transient. Less common but more serious effects include drug-induced liver injury, gallbladder-related events, and symptomatic reductions in free thyroxine. Seek medical advice promptly if you notice jaundice, severe abdominal pain, or unexplained fatigue.
The safety profile of Rezdiffra has been characterised primarily through the placebo-controlled, phase 3 MAESTRO-NASH trial, which enrolled more than 900 patients with biopsy-confirmed MASH and F2–F3 fibrosis and followed them for 52 weeks, and through multiple supporting studies of shorter duration. The overall tolerability profile in MAESTRO-NASH was favourable, with most adverse events being mild to moderate and few patients discontinuing due to side effects.
Gastrointestinal effects typically appear in the first 1–4 weeks of treatment and tend to lessen with time. Taking Rezdiffra at a consistent time, eating smaller meals, and maintaining hydration can help with symptom management. If gastrointestinal symptoms are severe or persistent, your doctor may consider temporary dose reduction to the 60 mg strength.
Serious Side Effects – Seek Urgent Medical Attention
Stop taking Rezdiffra and contact your doctor or emergency services immediately if you experience:
- Signs of liver injury – yellowing of the skin or eyes (jaundice), dark (tea-coloured) urine, pale stools, persistent nausea or vomiting, loss of appetite, right upper abdominal pain, unexplained fatigue, or easy bruising
- Severe allergic reactions – swelling of the lips, tongue, face, or throat; widespread rash or hives; difficulty breathing; chest tightness
- Gallbladder emergencies – sudden severe pain in the upper right abdomen, often after fatty meals, that may radiate to the back or right shoulder; fever; jaundice
- Severe skin reactions – widespread rash, blistering, peeling, or rash accompanied by fever, mouth sores, or swollen lymph nodes
- Symptoms suggestive of thyroid dysfunction – unusual cold intolerance, severe fatigue, weight gain, or new-onset depression (hypothyroidism); or tremor, palpitations, and heat intolerance (hyperthyroidism)
Side Effects by Frequency
Very Common
May affect more than 1 in 10 patients
- Diarrhoea
- Nausea
Common
May affect up to 1 in 10 patients
- Vomiting
- Abdominal pain or discomfort
- Constipation
- Pruritus (itching)
- Dizziness
- Mild to moderate elevations in ALT or AST
- Headache
- Flatulence
- Transient decreases in free thyroxine (T4) on laboratory testing
Uncommon
May affect up to 1 in 100 patients
- Clinically significant drug-induced liver injury
- Gallstones (cholelithiasis)
- Cholecystitis (gallbladder inflammation)
- Symptomatic hypothyroidism requiring thyroid hormone adjustment
- Muscle aches or weakness (especially if combined with statins)
- Urticaria or non-severe skin rash
- Reduction in blood cholesterol below therapeutic target (benefit, but may require lipid-therapy adjustment)
Rare
May affect up to 1 in 1,000 patients
- Severe hepatotoxicity with marked transaminase elevation and jaundice
- Severe hypersensitivity reactions, including angioedema
- Serious cutaneous adverse reactions
- Clinically relevant thyroid-function abnormalities
Frequency not known: long-term effects on bone mineral density, cardiovascular events, and hepatocellular carcinoma incidence are being evaluated in ongoing outcome studies and post-marketing surveillance. Patients and physicians are encouraged to report any suspected adverse reactions to their national pharmacovigilance authority (for example the FDA MedWatch program in the United States, the EudraVigilance system in Europe, or the MHRA Yellow Card scheme in the United Kingdom).
Changes in Laboratory Values
Beyond clinical symptoms, Rezdiffra produces predictable changes in laboratory values that reflect its mechanism of action:
- Reductions in LDL-cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides – generally considered beneficial but may require lipid therapy adjustment
- Reductions in liver fat on imaging (MR-PDFF, CAP on FibroScan®)
- Improvement in non-invasive fibrosis markers such as liver stiffness (kPa) and the ELF test
- Mild reductions in free T4 at the population level; most patients remain clinically euthyroid with normal TSH
How Should You Store Rezdiffra?
Store Rezdiffra tablets in their original container at room temperature (20–25°C or 68–77°F), protected from moisture and excessive heat. Keep out of the sight and reach of children. Do not use tablets after the expiry date printed on the pack. Return unused medicine to a pharmacy for safe disposal.
Follow these practical storage guidelines to keep Rezdiffra effective and safe:
- Temperature: Store at room temperature, typically 20–25°C (68–77°F). Short excursions between 15–30°C (59–86°F) are generally permitted
- Humidity and light: Keep the tablets in the original pack, tightly closed, to protect from moisture. Avoid storing in the bathroom or kitchen where humidity is high
- Child-resistant storage: Keep Rezdiffra out of the sight and reach of children, ideally in a locked cupboard. Accidental ingestion by a child requires immediate medical attention
- Check the expiry date: Do not use Rezdiffra after the expiry date printed on the carton and bottle (after “EXP”). The expiry date refers to the last day of the month
- Disposal: Do not dispose of unused Rezdiffra in household waste or wastewater. Ask your pharmacist how to dispose of medicines you no longer use – this helps protect the environment
- Travelling: Carry Rezdiffra in its original labelled container in your hand luggage when travelling. If travelling through different time zones, ask your pharmacist for advice on maintaining the once-daily schedule
What Does Rezdiffra Contain?
Each Rezdiffra film-coated tablet contains resmetirom as the active ingredient, in strengths of 60 mg, 80 mg, or 100 mg. The tablets are round to oval, film-coated, and debossed with the strength on one side. Apart from resmetirom, they contain standard tablet excipients such as microcrystalline cellulose, lactose, croscarmellose sodium, magnesium stearate, and a film-coating.
Active Substance
- Resmetirom 60 mg, 80 mg, or 100 mg per tablet – the liver-selective thyroid hormone receptor beta (THR-β) agonist
Other Ingredients (Excipients)
Tablet core: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, hydroxypropyl cellulose, sodium lauryl sulfate, colloidal silicon dioxide, and magnesium stearate.
Film coating: hypromellose, titanium dioxide, triacetin, and colouring agents (iron oxides). The exact coating composition and tablet colour may differ between strengths to aid identification.
Refer to the official prescribing information or patient leaflet supplied with your medicine for the full list of excipients, which may be important if you have known allergies or intolerances (for example lactose intolerance).
Appearance and Packaging
Rezdiffra is supplied as film-coated tablets packaged in bottles with child-resistant caps, typically containing 30 tablets per bottle. Each strength has a distinct appearance and embossing to minimise the risk of dosing error. Always check the strength before each dose.
Rezdiffra received accelerated approval from the US Food and Drug Administration on 14 March 2024. Regulatory review is ongoing in the European Union through the European Medicines Agency and in other jurisdictions. Availability, reimbursement, and specific prescribing restrictions may differ between countries. Consult your national regulatory authority or your prescriber for the most up-to-date local information.
Frequently Asked Questions About Rezdiffra
Rezdiffra (resmetirom) is a prescription medicine used together with diet and exercise to treat adults with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) who have moderate to advanced liver fibrosis (stages F2 to F3). It is the first and only medicine specifically approved for MASH. Rezdiffra reduces liver fat, inflammation, and fibrosis, but it does not replace weight management or treatment of related conditions such as type 2 diabetes, obesity, hypertension, and dyslipidaemia.
Resmetirom selectively activates the beta subtype of the thyroid hormone receptor (THR-β). THR-β is the dominant thyroid receptor in the liver and regulates fat metabolism. Activation increases hepatic fat oxidation and lipophagy, reduces triglyceride accumulation in liver cells, and over time reduces inflammation and fibrosis. Because resmetirom is liver-selective and largely avoids THR-α (which is expressed in the heart and bone), it does not cause the typical systemic effects of excess thyroid hormone such as tachycardia and bone loss.
The recommended dose is based on body weight. Adults weighing less than 100 kg (220 lb) take 80 mg once daily. Adults weighing 100 kg (220 lb) or more take 100 mg once daily. Rezdiffra is taken orally, with or without food, at about the same time each day. A 60 mg strength is available for dose modification if your prescriber determines that a lower dose is appropriate (for example due to side effects or drug interactions). Always follow your doctor’s instructions.
The most common side effects (affecting more than 1 in 10 patients) are diarrhoea and nausea, which are usually mild and transient. Common side effects include vomiting, abdominal pain, constipation, itching, dizziness, and headache. Rezdiffra can also cause elevations in liver enzymes and transient reductions in free thyroxine. Rare but serious side effects include drug-induced liver injury, severe hypersensitivity reactions, and gallbladder problems. Contact your doctor promptly if you develop jaundice, severe abdominal pain, or any other unexpected symptom.
Rezdiffra is contraindicated in patients with decompensated cirrhosis (Child-Pugh B or C) and in those who must take gemfibrozil or clopidogrel (strong CYP2C8 inhibitors). It should not be used during pregnancy without a careful risk-benefit discussion, and breastfeeding is generally not recommended. Rezdiffra should be used with caution in people who take statins (especially rosuvastatin and simvastatin) because of the increased risk of myopathy, and in patients with thyroid disease or significant gallbladder disease. The decision to start Rezdiffra should be made by a clinician experienced in managing MASH, typically a hepatologist or gastroenterologist.
MASH is a chronic, progressive condition, and Rezdiffra is not a cure. The duration of therapy is individualised and is determined by your hepatologist based on response, side effects, and evolving evidence. Ongoing outcome studies are evaluating long-term benefits on progression to cirrhosis, liver decompensation, transplantation, and liver-related death. If Rezdiffra is stopped, you will still need comprehensive management of your metabolic health, including lifestyle interventions and treatment of obesity, diabetes, and dyslipidaemia.
Alcohol contributes independently to liver injury and can worsen MASH. While there is no specific pharmacokinetic interaction between resmetirom and alcohol, most hepatologists recommend either complete abstinence or strict limits on alcohol intake while taking Rezdiffra and throughout the treatment of MASH. Heavy or chronic alcohol use combined with any drug metabolised by the liver can increase the risk of drug-induced liver injury. Discuss your specific situation with your doctor.
References
- US Food and Drug Administration (FDA). Rezdiffra (resmetirom) Full Prescribing Information. Madrigal Pharmaceuticals. Approved 14 March 2024. Available at: accessdata.fda.gov/drugsatfda_docs/label/2024/217785s000lbl.pdf
- Harrison SA, Bedossa P, Guy CD, et al. “A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis.” N Engl J Med. 2024;390(6):497–509. doi.org/10.1056/NEJMoa2309000
- Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. “AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease.” Hepatology. 2023;77(5):1797–1835.
- European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). “EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD).” J Hepatol. 2024;81(3):492–542.
- Harrison SA, Taub R, Neff GW, et al. “Resmetirom for nonalcoholic steatohepatitis – overview of the MAESTRO development program.” Contemp Clin Trials. 2023;125:107056.
- Karim G, Bansal MB. “Resmetirom: An Orally Administered, Smallmolecule, Liver-directed, β-selective THR Agonist for the Treatment of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis.” touchREVIEWS in Endocrinology. 2023;19(1):60–70.
- Rinella ME, Lazarus JV, Ratziu V, et al. “A multi-society Delphi consensus statement on new fatty liver disease nomenclature.” J Hepatol. 2023;79(6):1542–1556.
- World Health Organization (WHO). “Non-alcoholic fatty liver disease and its comorbidities: global overview.” Available at: who.int
- National Institute for Health and Care Excellence (NICE). “Non-alcoholic fatty liver disease (NAFLD): assessment and management” (NG49). Updated 2024.
Editorial Team
This article has been written and medically reviewed by the iMedic Medical Editorial Team, consisting of licensed specialist physicians with expertise in hepatology, endocrinology, and clinical pharmacology.
Our medical writers hold advanced degrees in medicine, pharmacology, or biomedical sciences and are experienced in translating complex clinical data from journals such as the New England Journal of Medicine, The Lancet, and Journal of Hepatology into accessible, evidence-based patient information.
All content undergoes rigorous peer review by board-certified hepatologists, endocrinologists, and pharmacists who verify clinical accuracy, alignment with current guidelines (AASLD, EASL, FDA, EMA, NICE), and evidence quality using the GRADE framework.
Evidence standard: All medical claims in this article are supported by Level 1A evidence (systematic reviews and randomised controlled trials, including the phase 3 MAESTRO-NASH study) or current international treatment guidelines. We have no commercial relationships with pharmaceutical companies, and all content is editorially independent.
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