This page shows what was measured, who it was measured in, and what that does not settle.
What Resmetirom does in the body
Liver fat falls, and on biopsy inflammation and scarring improve.
Thyroid hormone tells the liver to burn fat and clear cholesterol, but flooding the body with thyroid hormone damages heart and bone. Resmetirom is shaped to be taken up almost entirely by the liver and to prefer the version of the thyroid receptor the liver mostly uses, so it delivers that instruction to the liver and largely nowhere else.
Why people take it. Fatty liver disease with inflammation and moderate to advanced scarring
What happened in people
LDL cholesterol reduction of 13.6% and 16.3% from baseline against 0.1% on placebo at week 24
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
MAESTRO-NASH OUTCOMES: a phase 3 study to evaluate the effect of resmetirom on clinical outcomes in patients with well-compensated MASH cirrhosis (NCT05500222) · a recorded source, not a stored snapshot
The limit that matters most
Brand-only with no generic; the label restricts use to non-cirrhotic disease with fibrosis consistent with stages F2 to F3
Where it acts
Hepatocyte nucleus (liver)
Kind of result
A number that stands in for health
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · RE0V0T1ES0 · read 2026-08-29
Its recorded molecular formula is C17H12Cl2N6O4, weighing 435.22.
US prescribing information · e67ea09f-a840-439c-86c8-f98585f978b2 · read 2026-08-30
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 98 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
Placebo
A placebo is a dummy treatment given so the real one can be compared with it.
A picture of it, and where the picture fails
A placebo is like a blank control in an experiment.
Where that stops being true. A blank does nothing. People given a placebo often do get better.
What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.
An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Co-primary at week 52: NASH resolution with no worsening of fibrosis, and fibrosis improvement by at least one stage with no worsening of the NAFLD activity score
Resolution 25.9% and 29.9% against 9.7%; fibrosis improvement 24.2% and 25.9% against 14.2%; P < 0.001 for all four comparisons
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Both endpoints are histological readings at one year. No clinical outcome — cirrhosis, decompensation, hepatocellular carcinoma, transplantation or death — was measured. Placebo rates were 9.7% and 14.2%, reflecting lifestyle response, regression to the mean and biopsy variability.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, two strengths, dosed by body weight
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
MAESTRO-NASH OUTCOMES: a phase 3 study to evaluate the effect of resmetirom on clinical outcomes in patients with well-compensated MASH cirrhosis (NCT05500222) · a recorded source, not a stored snapshot
Drugs@FDA: REZDIFFRA (resmetirom), NDA 217785, accelerated approval 14 March 2024 (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.p… · a recorded source, not a stored snapshot
Incidence of treatment-emergent adverse events over 52 weeks
Treatment-emergent adverse events 86.1% and 88.4% against 81.8% on placebo; secondary lipid and hepatic fat endpoints P < 0.0001
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Enrolled patients with presumed rather than biopsy-confirmed disease, and measured imaging and laboratory endpoints rather than histology. The excess over placebo was diarrhoea and nausea at initiation.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, two strengths, dosed by body weight
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
MAESTRO-NASH OUTCOMES: a phase 3 study to evaluate the effect of resmetirom on clinical outcomes in patients with well-compensated MASH cirrhosis (NCT05500222) · a recorded source, not a stored snapshot
Drugs@FDA: REZDIFFRA (resmetirom), NDA 217785, accelerated approval 14 March 2024 (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.p… · a recorded source, not a stored snapshot
Composite of clinical outcomes in well-compensated MASH cirrhosis — as designed, not yet reported
✗ The study did not show it
Who was studied
MAESTRO-NASH OUTCOMES (NCT05500222)
How many people
845
Study design
Phase 3 clinical outcomes trial, active and not recruiting
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
No result. The trial is active and not recruiting as of August 2026, and is the confirmatory requirement attached to the accelerated approval.
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. `endpoint met: false` here means "no result exists yet", not "the endpoint was missed". The trial also enrols a cirrhotic population the current label excludes.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, two strengths, dosed by body weight
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
MAESTRO-NASH OUTCOMES: a phase 3 study to evaluate the effect of resmetirom on clinical outcomes in patients with well-compensated MASH cirrhosis (NCT05500222) · a recorded source, not a stored snapshot
Drugs@FDA: REZDIFFRA (resmetirom), NDA 217785, accelerated approval 14 March 2024 (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.p… · a recorded source, not a stored snapshot
What we know
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
□Living longer, or avoiding a major eventNo evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
□Symptoms and quality of lifeNo evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.1 registered measure of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
□AnimalsNo evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.No animal record is stored.
■Cells in a dishEvidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Resmetirom
What a person takes: Oral tablet, two strengths, dosed by body weight.
The measurement behind this step
Once daily with or without food. The strength used depends on body weight because exposure scales with it. Hepatic uptake through organic anion transporting polypeptides is what confines the drug largely to liver, and those same transporters are the basis of its interaction limits with certain statins.
Getting in
Swallowed, and taken up almost entirely by the liver
The molecule is built so that liver cells pull it in and other tissues largely do not. That is the whole reason it can be given at all.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Hepatic uptake is mediated by organic anion transporting polypeptides, principally OATP1B1 and OATP1B3, giving preferential distribution to liver. Resmetirom is a substrate and inhibitor of several transporters, so the label carries interaction limits with certain statins. Earlier thyromimetics failed in development because they reached heart and bone; transporter-driven hepatic selectivity is the design response.
MAESTRO-NASH OUTCOMES: a phase 3 study to evaluate the effect of resmetirom on clinical outcomes in patients with well-compensated MASH cirrhosis (NCT05500222) · a recorded source, not a stored snapshot
Reaching the cell
Inside the hepatocyte it reaches a receptor sitting on DNA
The target is not on the cell surface. It is a receptor already parked on the genes it controls, holding them switched off until a hormone arrives.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Thyroid hormone receptor beta, encoded by THRB, occupies thyroid hormone response elements as a heterodimer with the retinoid X receptor, bound to the corepressors NCoR and SMRT in the unliganded state. The beta isoform predominates in liver, while the alpha isoform predominates in heart and bone — the distinction that makes isoform selectivity a safety property.
MAESTRO-NASH OUTCOMES: a phase 3 study to evaluate the effect of resmetirom on clinical outcomes in patients with well-compensated MASH cirrhosis (NCT05500222) · a recorded source, not a stored snapshot
What it acts on
It activates the liver isoform and largely leaves the cardiac one alone
The drug is shaped to fit the version of the receptor the liver uses in preference to the version the heart and bones use, which is what stops it behaving like an overdose of thyroid hormone.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The dichlorinated diaryl ether core preserves the twisted conformation thyroid hormone adopts in the receptor pocket, while the pyridazinone and cyanoazauracil substitutions replace the phenol and amino acid groups of triiodothyronine. Together with hepatic uptake, this produces selective THRB agonism. Full thyroid hormone action through THRA in cardiac and skeletal tissue causes tachyarrhythmia and bone loss, which is why unselective thyromimetics were never usable.
MAESTRO-NASH OUTCOMES: a phase 3 study to evaluate the effect of resmetirom on clinical outcomes in patients with well-compensated MASH cirrhosis (NCT05500222) · a recorded source, not a stored snapshot
The change it makes
The liver burns more fat and clears more LDL
The activated receptor switches on genes for burning fat inside the cell and for building more LDL collection receptors on its surface. Liver fat falls and blood cholesterol falls with it.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Corepressor release and coactivator recruitment raise transcription of genes for mitochondrial and peroxisomal fatty acid beta-oxidation, mitochondrial biogenesis and autophagy, and upregulate LDLR and CPT1A. Hepatic triglyceride content falls, and reduced lipotoxic stress is the proposed route to less hepatocellular ballooning and lobular inflammation, and in turn to reduced fibrogenesis.
MAESTRO-NASH OUTCOMES: a phase 3 study to evaluate the effect of resmetirom on clinical outcomes in patients with well-compensated MASH cirrhosis (NCT05500222) · a recorded source, not a stored snapshot
What that does for a person
Biopsy scores improve at one year, and nothing clinical has yet been counted
A quarter to three tenths of patients had their steatohepatitis resolve and about a quarter had their scarring improve. Whether that means fewer people go on to liver failure is not yet known.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
At week 52, NASH resolution with no worsening of fibrosis occurred in 25.9% and 29.9% against 9.7%, and fibrosis improvement by at least one stage in 24.2% and 25.9% against 14.2%. Hepatic fat by imaging fell 28.8% and 33.9% at 52 weeks in MAESTRO-NAFLD-1. No trial has reported progression to cirrhosis, hepatic decompensation, hepatocellular carcinoma, transplantation or death.
MAESTRO-NASH OUTCOMES: a phase 3 study to evaluate the effect of resmetirom on clinical outcomes in patients with well-compensated MASH cirrhosis (NCT05500222) · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
No registered study measured anything of this kind.
Measured
Things only a test, a scale or a device shows.
maximum observed concentration at steady state
Meaningful
Things that change how a life goes, not only a number.
No registered study measured anything of this kind.
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
What it would be like to take◇Read from sources, not yet reviewed
How long anything takes
Nine different lengths of time that get confused with each other. None of them is worked out from another.
Before anything is noticed.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before a test result moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before performance moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
How long the result was watched.No finished study window is recorded for a study that tested this substance.
How long people took it.How long people actually took it is not stored. The study window is not the same thing.
How long people were followed.Follow-up length is not stored separately. It is never read off the study window, which would be a different thing.
How fast the body clears it. 4.5 hours hours
Read from the label, which states: “Elimination Resmetirom median terminal plasma half-life (t½) is 4.5 hours and the steady state apparent clearance (CL/F) is 17.5 (56.3%) L/h.”
How long effects linger.RNAWiki does not store this separately, and never works it out from another figure on this page.
Beyond the studies. Nothing is recorded about the long term.
The longest finished study sets the edge of what anyone measured.
A study window is not how long people took it, and neither is how long they were followed. Where RNAWiki holds only one of the three, it shows one.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults with biopsy-confirmed non-cirrhotic steatohepatitis and fibrosis at stage F2 or F3. Not indicated in cirrhosis, where it has not been shown to be safe or effective.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety and effectiveness of REZDIFFRA have not been established in pediatric patients.”
US prescribing information · e67ea09f-a840-439c-86c8-f98585f978b2 · read 2026-08-30
On older people, the label states: “In Trial 1, of the 594 patients with MASH who received at least one dose of REZDIFFRA, 149 (25%) were 65 years of age and older and 13 (2%) were 75 years of age and older [see Clinical Studies (14) ].”
US prescribing information · e67ea09f-a840-439c-86c8-f98585f978b2 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary There are no available data on REZDIFFRA use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.”
US prescribing information · e67ea09f-a840-439c-86c8-f98585f978b2 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There is no information regarding the presence of REZDIFFRA in human or animal milk, the effects on the breast-fed infant, or the effects on milk production.”
US prescribing information · e67ea09f-a840-439c-86c8-f98585f978b2 · read 2026-08-30
On people with reduced liver function, the label states: “The safety and effectiveness of REZDIFFRA have not been established in patients with MASH cirrhosis.”
US prescribing information · e67ea09f-a840-439c-86c8-f98585f978b2 · read 2026-08-30
On people with reduced kidney function, the label states: “The recommended dosage of REZDIFFRA in patients with mild, moderate, or severe renal impairment is the same as in patients with normal kidney function [see Clinical Pharmacology (12.3) ] .”
US prescribing information · e67ea09f-a840-439c-86c8-f98585f978b2 · read 2026-08-30
Where the result stopped carrying
No outcome has failed, because none has been measured — the confirmatory trial has not reported
Every earlier unselective thyromimetic was abandoned in development for cardiac and skeletal toxicity through the alpha receptor isoform
The placebo arm achieved fibrosis improvement in 14.2% of patients, which is the size of the background effect any histological trial in this disease has to beat
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Not established
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral tablet, two strengths, dosed by body weight
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
Once daily with or without food. The strength used depends on body weight because exposure scales with it. Hepatic uptake through organic anion transporting polypeptides is what confines the drug largely to liver, and those same transporters are the basis of its interaction limits with certain statins.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Diarrhoea and nausea were more frequent than placebo and cluster at treatment initiation. Serious adverse events in MAESTRO-NASH were 10.9% on 80 mg, 12.7% on 100 mg and 11.5% on placebo. The label carries warnings for drug-induced liver toxicity and for gallbladder-related adverse reactions, and restricts co-administered doses of certain statins because resmetirom affects the transporters that clear them. It has not been shown to be safe or effective in cirrhosis, which is outside the indication.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
MAESTRO-NASH OUTCOMES: a phase 3 study to evaluate the effect of resmetirom on clinical outcomes in patients with well-compensated MASH cirrhosis (NCT05500222) · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral tablet, two strengths, dosed by body weight
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
The strength used depends on body weight because exposure scales with it. Hepatic uptake through organic anion transporting polypeptides is what confines the drug largely to liver, and those same transporters are the basis of its interaction limits with certain statins.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
15 products list this as an active ingredient in the United States drug directory. 15 of them contain it and nothing else.
FDA National Drug Code directory · 43265-7779 · read 2026-08-29
They are sold as powder, tablet and tablet, coated, taken oral.
FDA National Drug Code directory · 43265-7779 · read 2026-08-29
The regulator's established pharmacologic class for it is breast cancer resistance protein inhibitors [moa], cytochrome p450 2c8 inhibitors [moa] and organic anion transporting polypeptide 1b1 inhibitors [moa].
FDA National Drug Code directory · 43265-7779 · read 2026-08-29
1 published label names it as an active ingredient. 1 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · e67ea09f-a840-439c-86c8-f98585f978b2 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · e67ea09f-a840-439c-86c8-f98585f978b2 · read 2026-08-29
REZDIFFRA is oral at 3 DOSAGE FORMS AND STRENGTHS REZDIFFRA Tablets: 60 mg: white oval-shaped film-coated tablets debossed with “P60” on one side and plain on the other side. 80 mg: yellow, oval-shaped, film-coated tablets debossed with “P8…, recorded as fda label in effect 2026-07-29 in the United States.
US prescribing information · e67ea09f-a840-439c-86c8-f98585f978b2 · read 2026-08-30
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Resmetirom studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That improving a liver biopsy score prevents cirrhosis, liver failure, liver cancer, transplantation or death — the premise of the accelerated approval and not yet tested
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the confirmatory outcome trial will validate the indicated population — it is enrolling patients with compensated cirrhosis, which the label excludes
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the LDL reduction translates into fewer cardiovascular events — no trial on this drug has counted one, in a population whose commonest cause of death is cardiovascular
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the 52-week histological effect is sustained — no longer-term biopsy comparison against placebo has been reported
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
MAESTRO-NASH: both histological endpoints beat placebo at 52 weeks
In plain words
Roughly a quarter to three tenths of patients had their steatohepatitis resolve on the drug against one in ten on placebo, and about a quarter had their scarring improve by at least one stage against one in seven.
What was measured
NASH resolution without worsening fibrosis, and fibrosis improvement by at least one stage, on liver biopsy at week 52
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
MAESTRO-NASH randomised patients 1:1:1 to once-daily resmetirom 80 mg, resmetirom 100 mg or placebo, with 966 forming the primary analysis population (322, 323 and 321 respectively). At week 52, NASH resolution — including a reduction of at least 2 points in the NAFLD activity score, which ranges from 0 to 8 — with no worsening of fibrosis was achieved in 25.9% on 80 mg and 29.9% on 100 mg against 9.7% on placebo, p<0.001 for both. Fibrosis improvement by at least one stage with no worsening of the NAFLD activity score was achieved in 24.2% and 25.9% against 14.2%, p<0.001 for both. LDL cholesterol fell 13.6% and 16.3% from baseline to week 24 against 0.1% on placebo, p<0.001 for both. Diarrhoea and nausea were more frequent on resmetirom. Serious adverse events were similar across groups: 10.9%, 12.7% and 11.5%.
Written into the record, not signed off as a reviewed claim
The approval rests on a biopsy score, and no clinical outcome has been measured
In plain words
Nothing in the trial that led to approval counted a death, a liver transplant, an episode of liver failure or a case of liver cancer. The endpoints were what a pathologist saw under a microscope at one year.
What was measured
That improving a liver biopsy score at one year prevents cirrhosis, liver failure or death — the premise of the accelerated approval, and the thing the confirmatory trial exists to test
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Both primary endpoints of MAESTRO-NASH are histological readings at week 52. The NAFLD activity score is a composite of steatosis, lobular inflammation and hepatocellular ballooning scored 0 to 8 by a pathologist; fibrosis staging is a separate ordinal scale. Both are subject to sampling variability — a liver biopsy samples roughly one fifty-thousandth of the organ — and to inter-reader variability, which the trial addressed by using paired reads but cannot eliminate. What was not measured at all: progression to cirrhosis, hepatic decompensation, hepatocellular carcinoma, liver transplantation and death. The drug received accelerated approval on 14 March 2024 precisely because the surrogate was accepted as reasonably likely to predict clinical benefit, with a confirmatory requirement attached. MAESTRO-NASH OUTCOMES (NCT05500222), a trial in compensated cirrhosis with a clinical composite, is active and has not reported.
Written into the record, not signed off as a reviewed claim
The placebo response was 9.7% and 14.2%, which is why the trial had to be this large
In plain words
Roughly one in ten placebo patients had their steatohepatitis resolve and one in seven had their scarring improve, without any drug at all. That is the background against which the drug effect has to be read.
What was measured
Placebo-arm rates of NASH resolution and fibrosis improvement at week 52, and the resulting absolute treatment differences
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the placebo arm, NASH resolution with no worsening of fibrosis occurred in 9.7% and fibrosis improvement by at least one stage in 14.2% at 52 weeks. Both figures reflect a mixture of genuine improvement on lifestyle intervention, regression to the mean, and biopsy sampling and reading variability in an organ where disease is patchy. The absolute treatment differences are therefore 16.2 and 20.2 percentage points for resolution at the two doses, and 10.0 and 11.7 points for fibrosis improvement. Those are substantial effects for a disease with no prior approved therapy. They also mean that in the fibrosis endpoint, roughly three in five patients who improved on the 100 mg dose would have been expected to improve anyway, which is what a 14.2% placebo rate implies.
Written into the record, not signed off as a reviewed claim
MAESTRO-NAFLD-1: a 52-week safety trial with lipid and imaging endpoints, not histology
In plain words
A companion trial of more than a thousand patients tested safety and measured cholesterol, liver fat by scan and liver stiffness. It did not use biopsies and did not measure inflammation or scarring directly.
What was measured
Treatment-emergent adverse event incidence, and changes in LDL cholesterol, apolipoprotein B, triglycerides, hepatic fat and liver stiffness at 52 weeks
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
MAESTRO-NAFLD-1 was a 52-week randomised double-blind placebo-controlled phase 3 trial with three double-blind arms — resmetirom 100 mg (n=325), 80 mg (n=327) and placebo (n=320) — plus an open-label 100 mg arm (n=171). The primary endpoint was incidence of treatment-emergent adverse events, which occurred in 86.1%, 88.4% and 81.8% of the double-blind arms and 86.5% of the open-label arm; the excess over placebo was diarrhoea and nausea at treatment initiation. Key secondary endpoints as least-squares mean differences from placebo at 80 mg and 100 mg were LDL cholesterol -11.1% and -12.6%, apolipoprotein B -15.6% and -18.0%, triglycerides -15.4% and -20.4%, 16-week hepatic fat -34.9% and -38.6% (all p<0.0001), liver stiffness -1.02 and -1.70, and 52-week hepatic fat -28.8 and -33.9. These are imaging and laboratory measures; the trial enrolled patients with presumed rather than biopsy-confirmed disease.
Written into the record, not signed off as a reviewed claim
The confirmatory outcome trial is running in a population the label excludes
In plain words
The trial that must prove clinical benefit is enrolling patients with cirrhosis. The approved indication stops short of cirrhosis. So the confirmation, when it comes, will be in a different group.
What was measured
That the confirmatory outcome trial will confirm benefit in the indicated non-cirrhotic F2-F3 population — it is enrolling patients with compensated cirrhosis, which the label excludes
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
MAESTRO-NASH OUTCOMES (NCT05500222) is a phase 3 trial evaluating the effect of resmetirom on clinical outcomes, with an estimated enrolment of 845 participants, listed as active and not recruiting. It enrols patients with well-compensated MASH cirrhosis. The approved indication, by contrast, covers non-cirrhotic disease with fibrosis consistent with stages F2 to F3, and the label states the drug has not been shown to be safe or effective in cirrhosis. If the outcome trial succeeds it will demonstrate clinical benefit in a population outside the current indication, and if it fails it will not directly refute the histological result in the indicated population. Either way the inference from one to the other is a bridging assumption, not a measurement. This is a factual description of two trial populations, not a criticism of the design, which is constrained by the fact that clinical events accrue too slowly at stage F2 to F3 to power a trial of reasonable size.
Written into the record, not signed off as a reviewed claim
The LDL reduction is real and is not what the drug was approved for
In plain words
Resmetirom lowers LDL cholesterol by around 13 to 16%, along with apolipoprotein B and triglycerides. That is a genuine effect on the thing most of these patients actually die of, and no trial has counted those events.
What was measured
Percentage change in LDL cholesterol, apolipoprotein B and triglycerides against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In MAESTRO-NASH the change in LDL cholesterol from baseline to week 24 was -13.6% on 80 mg and -16.3% on 100 mg against 0.1% on placebo, p<0.001 for both. In MAESTRO-NAFLD-1 the least-squares mean differences from placebo were LDL -11.1% and -12.6%, apolipoprotein B -15.6% and -18.0%, and triglycerides -15.4% and -20.4%. The mechanism is direct: thyroid hormone receptor beta activation in hepatocytes upregulates the LDL receptor and stimulates fatty acid oxidation, which is the same downstream programme statins and ezetimibe engage from different starting points. Cardiovascular disease rather than liver failure is the leading cause of death in this population, so a lipid effect of this size is potentially the most clinically consequential thing the drug does — and no trial has measured a cardiovascular event on this drug. A generic statin produces a larger LDL reduction for about 2.3 cents a tablet.
This order is fixed in code and does not count clicks or time on the page.
What is not here
4 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
The first approved treatment for MASH, granted accelerated approval on histology alone: steatohepatitis resolved in 25.9% and 29.9% at two doses against 9.7% on placebo, and fibrosis improved by at least one stage in 24.2% and 25.9% against 14.2%, with no clinical outcome measured and the confirmatory trial not yet reported.
Recorded evidence blocks (10)
Q1
What did Resmetirom's largest trial (1759 people) and its longest (8.8 years) measure?
1759 people in Resmetirom's largest registered study, 8.8 years in its longest registered window, measuring Area under the concentration-time curve during a dosing interval (tau) at steady state (AUC0-tau). ClinicalTrials.gov · 2026-09-01
7 phase1, 4 phase3, 3 phase2, 1 na or unstated, 1 phase4; NCT03900429; 2028-01; no ageing endpoint recorded. Last human test completed 2025, NCT07216313.
Interpretation These counts include studies where Resmetirom was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase1
7
phase3
4
phase2
3
na or unstated
1
phase4
1
Last recorded human testNCT07216313
2025-10-20
recorded 2026-09-01 · last checked 2026-09-04
Q2
Resmetirom was tested only in human — what did it show?
Resmetirom's half-life is 4.5 hours — which schedules were studied?
4.5 hours, the half-life Resmetirom's label states. openfda-label · e67ea09f-a840-439c-86c8-f98585f978b2 · 2026-08-30
Show the evidence
half life
4.5 hours hours; Elimination Resmetirom median terminal plasma half-life (t½) is 4.5 hours and the steady state apparent clearance (CL/F) is 17.5 (56.3%) L/h.
tmax
Table 5: Resmetirom Estimated Systemic Exposure at Steady State in Patients with MASH with Fibrosis (F2 and F3) Abbreviations: AUC t au,ss = area under the concentration-versus-time curve over one dosing interval at steady state; C max,ss = maximum concentration at steady state; CV = arithmetic coefficient of variation Parameter Resmetirom 80 mg Once Daily Mean (CV%) Resmetirom 100 mg Once Daily…
metabolism
Metabolism Resmetirom is metabolized by CYP2C8 and is not metabolized by other CYP enzymes in vitro.
recorded 2026-08-30 · last checked 2026-09-04
Q5
Could one person measure Resmetirom's effect on maximum observed concentration at steady state?
Maximum observed concentration at steady state: measured in Resmetirom's trials.
Interpretation maximum observed concentration at steady state is the recorded endpoint.
Show the evidence
biomarkers
maximum observed concentration at steady state; 2026-09-01
Week 52 Dual Primary Objectives: To determine the effect of 80 or 100 mg MGL-3196 vs matching placebo on liver biopsy (NASH CRN score) at Week 52 compared with Baseline; The effect of once daily, oral administration of resmetirom on the incidence of adverse events.; latest 2030-04-08
Show the evidence
Trial
NCT03900429
"A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis"; n 1759; "Week 52 Dual Primary Objectives: To determine the effect of 80 or 100 mg MGL-3196 vs matching placebo on liver biopsy (NASH CRN score) at Week 52 compared with Baseline"; 2028-01
NCT04951219
"A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)"; n 810; "The effect of once daily, oral administration of resmetirom on the incidence of adverse events."; 2027-04
NCT05500222
"A Phase 3 Study to Evaluate the Effect of Resmetirom on Clinical Outcomes in Patients With Well-compensated NASH Cirrhosis (MAESTRO-NASH-OUTCOMES)"; n 845; "Incidence Of adjudicated Composite Clinical Outcome event"; 2027-01
NCT07143968
"A Study to Evaluate the Use of Resmetirom in Participants With MASLD and HIV"; n 120; "Change from baseline in hepatic fat content at week 24"; 2027-11
NCT07249788
"Resmiterom Efficacy & Safety in Patients With MASH"; n 165; "FIB-4 and CAP score/LSM on fibroscan"; 2026-12-31
NCT07335601
"Study to Evaluate Resmetirom in Post-Liver Transplant Patients With MASH"; n 120; "Percent change from baseline in liver fat content (LFC) as assessed by MRI-PDFF at Week 28"; 2029-03
2 further recorded trials
NCT07541469
"Rezdiffra Pregnancy and Lactation Registry"; n 10; "Pregnancy and Infant Outcomes Among Women Exposed to Rezdiffra During Pregnancy and/or Lactation"; 2030-04-08
NCT07763015
"Study of Resmetirom in Children and Adolescents With MASH"; n 61; "Safety and tolerability of multiple ascending doses of resmetirom"; 2029-07
recorded 2026-09-01 · last checked 2026-09-04
Q7
Which 6 trials of Resmetirom posted no result?
Posted no result
6 of 6 completed trials
Registrations
NCT01367873, NCT01519531, NCT02542969, NCT02749578, NCT03220165 and NCT04197479
Completion dates
oldest 2011-10; newest 2023-01-06
Show the evidence
Trial
NCT01367873
2011-10
NCT01519531
2012-11
NCT02542969
2015-10
NCT02749578
2016-05
NCT03220165
2017-09-03
NCT04197479
2023-01-06
Q8
At the median, Resmetirom's trials enrolled 66.5 people — anything larger?
Median enrolment
66.5
Largest enrolment
1759
Registered trials counted
16
Q9
Resmetirom and BCRP, OATP1B1 and OATP1B3: shared by which compounds?
BCRP, OATP1B1 and OATP1B3 appear in Resmetirom's recorded interaction sentences, 4 in all. openfda-label+europepmc · 2026-08-30
Interpretation clinical_pharmacology
Show the evidence
CYP2C8
clinical_pharmacology
Metabolism Resmetirom is metabolized by CYP2C8 and is not metabolized by other CYP enzymes in vitro.
clinical_pharmacology
Drug Interaction Studies Clinical Studies Moderate CYP2C8 Inhibitors: Resmetirom C max increased 1.3-fold and AUC 1.7-fold following concomitant use of multiple doses of resmetirom 100 mg/day with clopidogrel (a moderate CYP2C8 inhibitor) at steady-state in healthy subjects [see Drug Interactions (7.1) ] .
clinical_pharmacology
In Vitro Studies CYP450 Enzymes: Resmetirom is an inhibitor of CYP2C8.
clinical_pharmacology
CYP2C8 Substrates: Pioglitazone (a CYP2C8 substrate) C max was unchanged and AUC increased 1.5-fold following concomitant use of a single oral dose of pioglitazone (15 mg) with resmetirom at steady state (100 mg/day) in healthy subjects [see Drug Interactions (7.2) ] .
recorded 2026-08-30 · last checked 2026-09-04
Q10
What is recorded about Resmetirom and AMPK?
"We examine key metabolism-based therapeutics-pioglitazone, GLP-1 receptor agonists, SGLT2 inhibitors, resmetirom and statins-to delineate how distinct upstream triggers converge on AMPK." — where Resmetirom and AMPK appear together. Europe PMC · pathway abstract search · 2026-07-01
"CONCLUSION: Resmetirom and CUR showed significant renoprotective benefits against GS-induced nephrotoxicity by alleviating oxidative stress, modulating mitochondrial dynamics, and restoring cellular signaling pathways involving AKT1, DRP1, mTOR, and FOXO1."
PMID 42152469
"Thus, Bya is a promising therapeutic natural compound for MASH, and selective inhibition of MTORC1 is a potential approach to treat this disease.<b>Abbreviations:</b> aa, amino acids; AAV, adeno-associated virus; Bio, biotin; Bio-Bya, biotin-conjugated Bya; BSA, bovine serum albumin; BW, body weight; Bya, byakangelicin; CETSA, cellular thermal shift assay; CHIP-atlas, chromatin…"
recorded 2026-07-01 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 9 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.