Skip to content

Benfluorex

  • Withdrawn substance
  • Withdrawn
  • Identity checked
  • Sources last checked 2026-09-04

This page shows what was measured, who it was measured in, and what that does not settle.

What Benfluorex does in the body

The leaflets thicken, stiffen and stop closing properly, so blood leaks backwards.

The body breaks benfluorex down into norfenfluramine, the same compound fenfluramine produces. Norfenfluramine switches on a serotonin receptor found on the cells inside heart valves, and those cells respond by multiplying and laying down fibrous tissue. The appetite-suppressing effect and the valve damage come from the same metabolite.

Why people take it. Formerly sold in France for blood fats and weight in diabetes.

What happened in people

Among 27 people with unexplained heart-valve leakage, 19 had taken benfluorex, compared with 3 of 54 controls.

Reviewed first-read answer

Where this came from

A person wrote this and a reviewer approved it against this exact record. It carries no effect size.

A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.

No source is stored against this line.

The limit that matters most

It was licensed for blood fats but was chemically and practically used as an appetite suppressant.

Where it acts
Cardiac valve interstitial cells; 5-HT2B receptors on mitral and aortic leaflets
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.

What the registries record it as

  • Its recorded molecular formula is C19H20F3NO2, weighing 351.4.

    PubChem record · 2318 · read 2026-08-29

Where each sentence above came from

A person wrote this explanation into the record, with the studies named in the path below.

A reviewer approved this sentence against this exact record and its sources.

The limit a reviewer approved as the one that matters most here.

The four opening statements run to 88 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.

Absolute difference

An absolute difference is how many more people in a hundred were affected.

A picture of it, and where the picture fails

It is like counting heads in two rooms of a hundred.

Where that stops being true. Heads are easy to count. Study results carry a margin of error too.

What people get wrong. It is confused with a percentage change, which can look far larger.

The arithmetic difference in event rates between arms.

Confidence interval

A confidence interval is the range the true answer is likely to sit in.

A picture of it, and where the picture fails

It is like a weather forecast giving a range rather than one number.

Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.

What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.

An interval estimate that would contain the true parameter in a stated proportion of repeated studies.

What happened in peopleRead 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.

Hospitalisation in 2007 and 2008 for valvular insufficiency of any cause, mitral insufficiency, aortic insufficiency, or valve replacement with cardiopulmonary bypass, in diabetic patients exposed to benfluorex in 2006

The study showed what it set out to show

Who was studied
SNIIRAM-PMSI linked national cohort study (Weill et al.)
How many people
1048173
Study design
National comparative cohort study using linked insurance and hospitalisation databases
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Any valvular insufficiency: crude relative risk 2.9 (95% CI 2.2 to 3.7), adjusted 3.1 (2.4 to 4.0); mitral 2.5 (1.9 to 3.7); aortic 4.4 (3.0 to 6.6); valve replacement 3.9 (2.6 to 6.1)
Repeated elsewhere
Replicated

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. Only 4.1 per cent of the cohort was exposed, and the analysis covers hospitalisations in the two years following exposure, so subclinical and later-presenting disease is not captured.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral tablet

Interval reported. 95% CI 2

Written into the record, not signed off as a reviewed claim.

Benfluorex exposure in patients with unexplained mitral regurgitation versus matched controls with explained mitral regurgitation

The study showed what it set out to show

Who was studied
Hospital case-control study of unexplained mitral regurgitation (Frachon et al.)
How many people
81
Study design
Single-centre matched case-control study, 2003-2009
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Benfluorex reported in 19 of 27 cases against 3 of 54 controls; odds ratio 17.1 (95% CI 3.5 to 83), adjusted for body mass index, diabetes and dexfenfluramine use
Repeated elsewhere
Replicated

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. Twenty-seven cases from 682 eligible patients at a single centre gives a wide confidence interval, from 3.5 to 83. Exposure was assessed blind to case status, which addresses the principal bias of the design.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral tablet

Interval reported. 95% CI 3

Written into the record, not signed off as a reviewed claim.

What we know
RNAWiki holds 2 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 it changes in the bodyRead 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.

  1. Start

    Benfluorex

    What a person takes: Oral tablet.

    The measurement behind this step

    Oral benfluorex hydrochloride prescribed as an adjunct for hypertriglyceridaemia and for overweight in diabetes, frequently over extended periods. The benzoate ester is hydrolysed and the molecule N-dealkylated to norfenfluramine, which is the pharmacologically decisive species.

  2. Getting in

    An oral tablet, often taken for years

    Taken by mouth, prescribed for triglycerides or for weight in diabetes, frequently over long periods.

    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

    Oral benfluorex hydrochloride, prescribed as an adjunct in hypertriglyceridaemia and overweight in diabetes. Long treatment durations mean cumulative exposure, which the cohort data show is what drives the risk.

  3. Reaching the cell

    Metabolised to norfenfluramine

    The liver strips off part of the molecule, leaving the same compound fenfluramine leaves behind.

    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

    Hydrolysis of the benzoate ester and N-dealkylation yield norfenfluramine, the shared active metabolite of the fenfluramine series. Systemic exposure to the metabolite is what determines the valve risk, not the parent concentration.

  4. What it acts on

    Norfenfluramine agonises 5-HT2B on valve cells

    That metabolite switches on a serotonin receptor found on the cells inside heart valve leaflets.

    Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.

    The measurement behind this step

    Norfenfluramine is an agonist at 5-HT2B, a Gq-coupled receptor expressed on cardiac valve interstitial cells and largely absent from adult myocardium. The same receptor is the mechanism of ergot and carcinoid valve disease.

  5. The change it makes

    Valve interstitial cells proliferate and lay down fibrous tissue

    Those cells are told to multiply and produce matrix, so the leaflets thicken and stiffen.

    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

    5-HT2B-driven mitogenesis and transforming growth factor beta signalling produce plaque-like leaflet thickening with glycosaminoglycan deposition, apical displacement of coaptation and failure of leaflet closure.

  6. What that does for a person

    Regurgitation, hospitalisation and valve replacement

    Blood leaks backwards through the valve. In the French national data, exposed patients were three times as likely to be hospitalised for it and four times as likely to need surgery.

    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

    Measured: adjusted relative risk 3.1 (95% CI 2.4 to 4.0) for hospitalisation with any valvular insufficiency, 4.4 (3.0 to 6.6) for aortic insufficiency, 3.9 (2.6 to 6.1) for valve replacement surgery. Measured: odds ratio 17.1 (3.5 to 83) for benfluorex exposure in unexplained mitral regurgitation.

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 is missing or unclearRead 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.

  • Nobody. It was withdrawn in France in 2009 and its European authorisations were revoked. It never held a United States or United Kingdom licence.

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.

Where the result stopped carrying

  • Marketed from 1976 and withdrawn in France only in November 2009, twelve years after fenfluramine went for the same metabolite
  • Never approved in the United States or the United Kingdom, so the exposure was concentrated in the jurisdictions that licensed it
  • The 5-HT2B mechanism was established in 1997 and applied to a drug producing the same metabolite only in 2009
  • 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 takeRead 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 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 (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
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 takeRead 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

Withdrawn

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

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

Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Suppression classes recorded: S8.

No source is stored against this line.

What is in the pack

Oral benfluorex hydrochloride prescribed as an adjunct for hypertriglyceridaemia and for overweight in diabetes, frequently over extended periods. The benzoate ester is hydrolysed and the molecule N-dealkylated to norfenfluramine, which is the pharmacologically decisive species.

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

Not recorded.

Nothing recorded

Where this came from

RNAWiki holds nothing here and says so rather than guessing.

No register entry is recorded.

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 takeRead 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

Withdrawn in France in November 2009 for drug-induced valvular heart disease. In the linked national cohort of 1,048,173 diabetic patients, exposure carried an adjusted relative risk of 3.1 for hospitalisation with valvular insufficiency, 4.4 for aortic insufficiency and 3.9 for valve replacement surgery, with lower risk at lower cumulative dose. In a hospital case-control study the adjusted odds ratio for unexplained mitral regurgitation was 17.1. The mechanism is 5-HT2B agonism by the metabolite norfenfluramine, identical to that of fenfluramine. Pulmonary arterial hypertension is the other harm associated with the fenfluramine series.

Nobody counted how many people took this and were fine, so this cannot be turned into a rate.

Where this came from

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 unclearNothing found in the sources checked

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

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 benzoate ester is hydrolysed and the molecule N-dealkylated to norfenfluramine, which is the pharmacologically decisive species.

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.

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 takeRead 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.

Self-experiment planning is not offered for a prescription or clinician-supervised medicine, withdrawn medicine. The questions below are for a clinician or pharmacist.

Questions worth asking

  • Which of the trials of Benfluorex 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 unclearRead 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 a metabolic indication distinguishes benfluorex pharmacologically from the anorectics withdrawn in 1997

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 two-year hospitalisation window captures the full burden; subclinical and later-presenting valve disease is outside it

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 unclearRead from sources, not yet reviewed

What nobody knows yet

Open questions, each with why it is open and what would close it.

How much did people take in the studies?

The sources RNAWiki checked hold nothing for this field.

Why it matters. A result belongs to an amount. Without the amount the result floats free.

What would answer it

A stored source that records 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 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.

Formulation uncertainty

Several salts, forms or products of Benfluorex are recorded. Results from one form may not transfer to another.

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 peopleRead 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.

Odds ratio 17.1 for unexplained mitral regurgitation
In plain words
In a hospital case-control study, 19 of 27 patients with otherwise unexplained mitral valve leakage had taken benfluorex, against 3 of 54 controls.
What was measured
Adjusted odds ratio for benfluorex exposure in unexplained versus explained mitral regurgitation
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A case-control study screened patients admitted to cardiology or cardiac surgery units at a French hospital between 1 January 2003 and 30 June 2009 with mitral insufficiency diagnostic codes. Patients with a primary cause — degenerative, rheumatic, infectious endocarditis, congenital, radiation-induced, connective tissue or vasculitic disease, trauma, tumour — or a secondary functional cause were classed as having explained regurgitation; the remainder were cases. Each case was matched to two controls by sex and nearest date of birth from the explained group, with drug exposure assessed blind to case status. Of 682 eligible patients, 27 cases and 54 matched controls were identified. Benfluorex use was reported in 19 of 27 cases against 3 of 54 controls, odds ratio 17.1 (95% CI 3.5 to 83), adjusted for body mass index, diabetes and dexfenfluramine use.
Source
Frachon I, Etienne Y, Jobic Y, Le Gal G, Humbert M, Leroyer C. PLoS One 2010;5:e10128
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
A million-patient national cohort: relative risk 3.1, and 3.9 for valve replacement
In plain words
Linking French national insurance and hospital records for over a million diabetic patients, those exposed to benfluorex were about three times as likely to be hospitalised with a leaking valve and about four times as likely to need valve replacement surgery.
What was measured
Adjusted relative risk of hospitalisation for valvular insufficiency and valve replacement surgery with benfluorex exposure
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A French comparative cohort study linked the national health insurance database (SNIIRAM) and the hospitalisation database (PMSI). Patients aged 40 to 69 reimbursed for oral antidiabetic drugs or insulin in 2006 were eligible; exposed patients had at least one benfluorex reimbursement in 2006. Admission diagnoses of interest in 2007 and 2008 were valvular insufficiency of any cause, mitral insufficiency, aortic insufficiency, and valve replacement with cardiopulmonary bypass. Of 1,048,173 diabetic patients, 43,044 (4.1 per cent) were exposed. Hospitalisation for any cardiac valvular insufficiency was more frequent in the exposed: crude relative risk 2.9 (95% CI 2.2 to 3.7), adjusted 3.1 (2.4 to 4.0) after adjustment for sex, age and history of chronic cardiovascular disease, with lower risk at lower cumulative dose. Adjusted relative risk was 2.5 (1.9 to 3.7) for mitral insufficiency, 4.4 (3.0 to 6.6) for aortic insufficiency and 3.9 (2.6 to 6.1) for valve replacement surgery.
Source
Weill A et al. Pharmacoepidemiol Drug Saf 2010;19:1256-1262
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
A dose-response relationship, in a database of a million people
In plain words
Patients who had taken less benfluorex were at lower risk. That gradient is what turns an association into a strong causal case.
What was measured
Risk of valvular hospitalisation by cumulative benfluorex dose within the exposed cohort
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The national cohort reported lower risk of hospitalisation for valvular insufficiency in patients with lower cumulative benfluorex dose. A monotonic exposure-response gradient within an exposed population is one of the strongest features an observational study can present, because the most common alternative explanations — confounding by indication, surveillance bias — do not naturally produce a gradient within the exposed. Combined with a known mechanism through a shared metabolite and a hospital case-control odds ratio of 17.1 from independent investigators using a different design, the case does not depend on any single study.
Source
Weill A et al. Pharmacoepidemiol Drug Saf 2010;19:1256-1262
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Twelve years after fenfluramine, on a shared metabolite
In plain words
Fenfluramine was withdrawn worldwide in 1997 for valve damage. Benfluorex, which the body converts into the same damaging compound, stayed on the French market until 2009.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Fenfluramine and dexfenfluramine were withdrawn in 1997 after valvular heart disease was traced to 5-HT2B agonism by their metabolite norfenfluramine. Benfluorex is metabolised to the same compound. The published case-control study describes benfluorex explicitly as a fenfluramine derivative used in overweight diabetic patients and dyslipidaemia, and its own adjustment model includes dexfenfluramine exposure as a covariate — the investigators treated the two as sharing a risk pathway. It remained marketed in France until November 2009. The interval is not explained by absence of a mechanism, because the mechanism was established in 1997 for the metabolite this drug produces.
Source
Frachon I et al. PLoS One 2010;5:e10128; Weill A et al. Pharmacoepidemiol Drug Saf 2010;19:1256-1262
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
A metabolic indication for a molecule whose pharmacology is anorectic
In plain words
It was licensed as a drug for blood fats and for weight in diabetes. Chemically it is an appetite suppressant, and that is largely how it was used.
What was measured
That a metabolic indication makes a serotonergic anorectic something other than a serotonergic anorectic
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Benfluorex held indications for hypertriglyceridaemia and for overweight in diabetes. Its structure is a fenfluramine derivative and its active metabolite is norfenfluramine, the serotonergic anorectic metabolite. Marketing a compound of that class under a metabolic indication changes which regulatory precedents apply to it, which comparators it is judged against, and which safety literature is treated as relevant — even though the pharmacology is unchanged. The 1997 anorectic withdrawals did not automatically attach to a drug filed as a lipid agent. Whether an indication reflects the pharmacology or reframes it is a question the evidence record can and should ask.
Source
Frachon I et al. PLoS One 2010;5:e10128 — benfluorex described as a fenfluramine derivative used in overweight diabetic patients and dyslipidaemia
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
The record-linkage method was itself a finding
In plain words
The French investigators established the size of the harm by linking national prescription records to national hospital records, and said so as a conclusion in its own right.
What was measured
Complete national exposed population of 43,044 within 1,048,173 diabetic patients, identified by record linkage
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The cohort authors state as a conclusion that linkage between the SNIIRAM insurance database and the PMSI hospitalisation database is a valuable tool in France for quantifying the risk of serious adverse drug reactions. That is a methodological result alongside the pharmacological one. A country with linked, complete prescription and admission records can measure the size of a drug harm across its entire exposed population without assembling a study cohort, which is what made a relative risk of 3.1 available on 1,048,173 patients. The equivalent question in a fragmented health system requires either a much larger effect or a much longer wait.
Source
Weill A et al. Pharmacoepidemiol Drug Saf 2010;19:1256-1262
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The third drug on this page destroyed by 5-HT2B
In plain words
Fenfluramine in 1997, pergolide in 2007, benfluorex in 2009. Three different drugs for three different conditions, one receptor.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Fenfluramine was withdrawn for valvular disease via norfenfluramine at 5-HT2B. Pergolide was withdrawn in 2007 for valvular disease via ergoline 5-HT2B agonism, with clinically important regurgitation in 23.4 per cent of treated patients on echocardiography. Benfluorex was withdrawn in 2009 for valvular disease via the same metabolite as fenfluramine. The indications were obesity, Parkinson's disease and hypertriglyceridaemia — nothing in common. What they share is a receptor on valve interstitial cells that responds to agonism by proliferating. A 5-HT2B functional counter-screen costs almost nothing and answers the question directly, which is why it is now standard for any candidate with serotonergic or ergoline chemistry.
Source
Frachon I et al. PLoS One 2010;5:e10128; Zanettini R et al. N Engl J Med 2007;356:39-46
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim

Checks this page had to pass

  • Passed

    Identity resolved

    no open identity hold

  • Passed

    No unresolved merge across substance families

    no quarantine open

  • Passed

    Every public sentence names a source

    The opening statement carries the origin: Written into the record, not signed off.

  • Not passed

    Trial roles classified for highlighted evidence

    No registered study is classified as testing this substance.

  • Passed

    No internal keys in reader text

    enforced by the copy-contract test over the rendered page

  • Passed

    Safety mode resolved

    Suppression classes recorded: S8.

  • Passed

    Canonical metadata present

    slug and display name present

What is missing or unclearRead from sources, not yet reviewed

How this medicine reached us

Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.

  1. Withdrawn in European Union, 2009, for "respiratory toxicity" (ChEMBL; Open Targets)

  2. Withdrawn in European Union, 2009, for "cardiotoxicity" (ChEMBL; Open Targets)

What is missing or unclearRead from sources, not yet reviewed

What to learn next

Ordered by what would most change how you read this page, starting with what is easiest to misunderstand.

This order is fixed in code and does not count clicks or time on the page.

What is not here

7 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.
  • How close this is to real life — found nothing in the sources checked.
  • Felt, measured, or meaningful — found nothing in the sources checked.
  • How long anything takes — 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.

A fenfluramine derivative sharing fenfluramine's valve-damaging metabolite, withdrawn in France in November 2009 — twelve years after fenfluramine — with a case-control odds ratio of 17.1 for unexplained mitral regurgitation and, in a cohort of 1,048,173 diabetic patients, an adjusted relative risk of 3.1 for hospitalisation with valvular insufficiency and 3.9 for valve replacement surgery.

Recorded evidence blocks (4)

1 registered trial of Benfluorex — at which phase?


Registered studies posting no result
1 of 1

1 registered study of Benfluorex: 1 phase2. CLINICALTRIALS_SNAPSHOT · 2026-09-01

23 with a PubMed record

Show the evidence
  • phase2
    1
  • unknown
    1

recorded 2026-09-01 · last checked 2026-09-04

Approved in 1974, withdrawn in 2009: what happened to Benfluorex in European Union?


Approved 1974, withdrawn 2009 in European Union; the register's words: "respiratory toxicity". Open Targets drug warning · CHEMBL400599 · 2026-06-24

4 recorded reasons; European Union

Show the evidence

Reason

  • "respiratory toxicity"
  • "cardiotoxicity"
  • "respiratory toxicity"
  • "cardiotoxicity"

recorded 2026-06-24 · last checked 2026-09-04

At the median, Benfluorex's trials enrolled 240 people — anything larger?


Median enrolment
240
Largest enrolment
240
Registered trials counted
1

What do 4 spontaneous reports say about Benfluorex — and not say?


These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.

Benfluorex appears in spontaneous reports to regulators. Across the 1 most-reported reaction term, 4 reaction mentions were counted: ventricular fibrillation 4. FAERS via Open Targets · CHEMBL400599 · 2026-06-24

Show the evidence
  • ventricular fibrillation
    4

recorded 2026-06-24 · last checked 2026-09-04

Where it is registered

Where it’s registered

Withdrawn in European Union, 2009, for "respiratory toxicity" (ChEMBL; Open Targets)

Withdrawn in European Union, 2009, for "cardiotoxicity" (ChEMBL; Open Targets)

Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL400599
PubChem CID
2318
CAS number
23602-78-0
RxCUI
18880
InChIKey
CJAVTWRYCDNHSM-UHFFFAOYSA-N
Also called
Mediaxal, BENFLUOREX [MI], Benfluorex [WHO-DD], benfluorex [INN]
Development code
NSC-757396
Trade name
Mediator
Sources (4)

Sources

ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0

How these records are assembled · Which registers were checked

Index-quality checks
  • identity passed: no open identity hold
  • 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: 4 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.