This page shows what was measured, who it was measured in, and what that does not settle.
What Troglitazone does in the body
A tablet for type 2 diabetes that made the body respond to insulin
Fat cells carry a switch that decides how much fat they store and how sensitively the whole body responds to insulin. Troglitazone flips that switch on. Fat gets pulled back into fat cells and out of muscle and liver, so insulin starts working again and blood sugar falls without the pancreas being pushed harder. The liver injury was separate from all of that: an unpredictable reaction, in a minority of patients, that could go from normal liver tests to irreversible failure inside a month.
What happened in people
Diabetes incidence 3.0 versus 12.0 cases per 100 person-years against placebo in the Diabetes Prevention Program
✎ 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.
The case is the standard example that a laboratory monitoring requirement is a risk-management strategy only if patients actually receive the tests and the injury is slow enough for the tests to catch it
Where it acts
Adipocyte and hepatocyte nuclei; the toxicity site is the hepatocyte
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. It is a prescription or clinician-administered medicine where it is approved.
What the registries record it as
Its recorded molecular formula is C24H27NO5S, weighing 441.5.
PubChem record · 5591 · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 117 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.
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.
Enzyme
An enzyme is a protein that speeds up one chemical change.
A picture of it, and where the picture fails
An enzyme is like a machine on a production line doing one cut.
Where that stops being true. A machine is switched on and off by a person. Enzymes are controlled by the cell.
What people get wrong. Enzymes are thought to be used up. They are not; they work again and again.
A catalytic protein that lowers the activation energy of a specific reaction.
Receptor
A receptor is a part of a cell that a signal fits into.
A picture of it, and where the picture fails
A receptor is like a lock waiting for one key.
Where that stops being true. A lock either opens or does not. A receptor can be half-triggered, or worn out.
What people get wrong. Fitting a receptor is read as causing a benefit. It causes a step, and nothing more.
A protein that binds a specific ligand and converts that binding into a cellular response.
Pathway
A pathway is a chain of steps inside a cell, each one setting off the next.
A picture of it, and where the picture fails
A pathway is like a row of dominoes.
Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.
What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.
An ordered series of molecular interactions producing a defined cellular change.
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.
Incidence of type 2 diabetes across four arms — troglitazone, metformin, placebo and intensive lifestyle intervention
✓ The study showed what it set out to show
Who was studied
Diabetes Prevention Program, troglitazone arm
How many people
2343
Study design
Phase 3 randomised prevention trial
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
3.0 versus 12.0 cases/100 person-years against placebo, P < 0.001; versus metformin 6.7, P = 0.02; versus lifestyle 5.1, P = 0.18
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. The troglitazone arm was terminated in June 1998 after a mean 0.9 years for liver toxicity, so the comparison rests on a much shorter exposure than the other three arms. The prevention effect did not persist after withdrawal.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, once daily with food (200, 300 and 400 mg)
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Clinical features, time course and cumulative incidence of troglitazone-associated liver failure
✓ The study showed what it set out to show
Who was studied
FDA liver failure case series (Graham et al.)
How many people
94
Study design
Postmarketing case series with survival analysis
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Not a hypothesis test; estimated number needed to harm 600 to 1,500 patients at 26 months after adjustment for under-reporting
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. Nineteen patients progressed from normal liver function to irreversible injury within one month and were clinically indistinguishable beforehand from those with a longer course.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, once daily with food (200, 300 and 400 mg)
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
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 eventEvidence recorded. Death, a heart attack, a stroke, a hospital stay.2 registered measures of this kind. No reviewed result.
□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 healthNo evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.No registered study measures this.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Mouse, Rat. A result in animals says what to test next. It does not say what happens in people.
■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
Troglitazone
What a person takes: Oral tablet, once daily with food (200, 300 and 400 mg).
The measurement behind this step
Once-daily lipophilic tablet whose absorption depends on being taken with a meal. Hepatic metabolism by sulfation and glucuronidation with a CYP3A4 oxidative route; troglitazone is also a CYP3A4 inducer, which reduced the exposure of co-administered oral contraceptives.
Getting in
A once-daily tablet with food
Taken once a day with a meal, because it is fat-soluble and absorbed much better that way.
╌╌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
Highly lipophilic; oral absorption is substantially increased by food. Extensively metabolised in the liver, principally by sulfation and glucuronidation with a CYP3A4-mediated oxidative route that generates the reactive species.
Enters fat cells and liver cells and reaches the nucleus
Because it is greasy it passes straight through cell membranes and into the cell nucleus, where the switch it acts on lives.
╌╌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
Passive diffusion into adipocytes, hepatocytes and skeletal muscle. The target is a nuclear receptor, so the drug must reach the nuclear compartment rather than a surface receptor.
Binds PPAR-gamma and recruits the transcription machinery
It clamps onto a protein that sits on DNA and turns a whole programme of genes on at once.
╌╌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 thiazolidinedione head binds the PPAR-gamma ligand-binding domain, stabilising helix 12, releasing corepressors and recruiting coactivators. The PPAR-gamma:RXR heterodimer then drives transcription at peroxisome proliferator response elements.
Fat is redistributed and insulin sensitivity returns
Fat is pulled back into fat cells and out of muscle and liver, so insulin starts working properly again without the pancreas being pushed harder.
╌╌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
Upregulation of adipocyte lipid storage genes, adiponectin secretion and GLUT4 expression, with reduced circulating free fatty acids and reduced ectopic lipid in liver and skeletal muscle. In DPP the effect was attributed to improved insulin sensitivity with maintenance of insulin secretion; in TRIPOD it was closely tied to reduced endogenous insulin requirement at three months.
Diabetes incidence falls; in a minority, the liver fails
New diabetes dropped to a quarter of the placebo rate. In a much smaller number of people the liver failed, sometimes within a month of being normal.
╌╌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 endpoints: 3.0 versus 12.0 diabetes cases per 100 person-years in DPP, 5.4% versus 12.1% annual incidence in TRIPOD, against 94 reported liver failures with 13% of acute cases recovering without transplantation and a number needed to harm of 600 to 1,500 at 26 months.
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.
No registered study measured anything of this kind.
Meaningful
Things that change how a life goes, not only a number.
hospitalization for incident heart failure
hospitalization for acute pancreatitis
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.
Names that fit none of the three (1)
incident pancreatic cancer
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
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.
Nobody now. Pioglitazone and rosiglitazone, which share the mechanism without the hepatotoxicity, took its place from 1999.
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
Withdrawn in the United Kingdom within weeks of its 1997 European launch on liver toxicity grounds
The Diabetes Prevention Program terminated its troglitazone arm in June 1998, less than two years into the trial
United States withdrawal on 21 March 2000, after over US$2 billion of sales
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
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, once daily with food (200, 300 and 400 mg)
✎ 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. It is a prescription or clinician-administered medicine where it is approved.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
A register records the withdrawal of an approval.
No source is stored against this line.
What is in the pack
Once-daily lipophilic tablet whose absorption depends on being taken with a meal. Hepatic metabolism by sulfation and glucuronidation with a CYP3A4 oxidative route; troglitazone is also a CYP3A4 inducer, which reduced the exposure of co-administered oral contraceptives.
✎ 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
Withdrawn from the United States on 21 March 2000 for idiosyncratic hepatocellular injury progressing to acute liver failure. The measured harms are 94 reported liver failure cases, 67% of acute cases in women, 13% recovering without transplantation, and an estimated number needed to harm of 600 to 1,500 at 26 months. Risk was elevated from the first month through at least the 26th, and progression to irreversibility within a single month was documented.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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∅Nothing 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, once daily with food (200, 300 and 400 mg)
✎ 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
Hepatic metabolism by sulfation and glucuronidation with a CYP3A4 oxidative route; troglitazone is also a CYP3A4 inducer, which reduced the exposure of co-administered oral contraceptives.
✎ 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 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.
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 Troglitazone 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 monthly aminotransferase monitoring could prevent troglitazone hepatic failure, when 19 documented patients went from normal to irreversible inside one month
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 fulminant hepatotoxicity was a PPAR-gamma class effect rather than a property of troglitazone's chromanol tail
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 a prevention effect measured during treatment implies a lasting change in disease course — DPP showed the incidence returned to placebo levels after withdrawal
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.
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.
How fast does the body clear it?
The sources RNAWiki checked hold nothing for this field.
Why it matters. Without this, nothing on this page can say how long anything lasts.
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 Troglitazone 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 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.
DPP: 3.0 versus 12.0 diabetes cases per 100 person-years against placebo
In plain words
In the largest diabetes prevention trial ever run, troglitazone cut new diabetes to a quarter of the placebo rate. It beat metformin. It also beat the intensive lifestyle programme, though not significantly.
What was measured
Diabetes incidence per 100 person-years during troglitazone exposure
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Diabetes Prevention Program randomised participants from 1996 to 1998 to metformin (n=587), troglitazone (n=585), double placebo (n=582) or intensive lifestyle intervention (n=589). The troglitazone arm was discontinued in June 1998 over liver toxicity, after a mean 0.9 years of treatment (range 0.5 to 1.5 years). During that exposure the diabetes incidence rate was 3.0 cases per 100 person-years on troglitazone against 12.0 on placebo (p<0.001), 6.7 on metformin (p=0.02 favouring troglitazone) and 5.1 on intensive lifestyle (p=0.18). The mechanism was improved insulin sensitivity with maintained insulin secretion.
Written into the record, not signed off as a reviewed claim
The prevention effect vanished the moment the drug stopped
In plain words
In the three years after the troglitazone arm was stopped, new diabetes appeared at almost exactly the placebo rate. The drug had suppressed the disease, not altered its course.
What was measured
Diabetes incidence in the three years after troglitazone withdrawal
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Following withdrawal of troglitazone in June 1998, the DPP continued follow-up of all participants. Over the subsequent three years the diabetes incidence rate in the former troglitazone group was almost identical to that of the placebo group. The authors' conclusion is precise and worth quoting in structure: troglitazone "markedly reduced the incidence of diabetes during its limited period of use, but this action did not persist." Whether a longer safe exposure to another thiazolidinedione would produce a durable effect they explicitly left undetermined.
Written into the record, not signed off as a reviewed claim
TRIPOD: annual diabetes incidence halved in women with prior gestational diabetes
In plain words
In 266 Hispanic women who had had diabetes in pregnancy, the yearly rate of developing type 2 diabetes fell from 12.1% to 5.4%. Here the protection did persist for eight months after stopping.
What was measured
Average annual diabetes incidence over a median 30 months
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Double-blind randomisation of women with previous gestational diabetes to placebo (n=133) or troglitazone 400 mg daily (n=133), with oral glucose tolerance tests annually and intravenous glucose tolerance tests at baseline and three months. Among the 236 women who returned for at least one follow-up visit, average annual diabetes incidence over a median 30 months on blinded medication was 12.1% on placebo and 5.4% on troglitazone (p<0.01). Protection was closely related to the reduction in endogenous insulin requirement at three months, persisted eight months after study medication stopped, and was associated with preserved beta-cell compensation for insulin resistance.
Written into the record, not signed off as a reviewed claim
94 cases of liver failure; 13% of acute cases recovered without transplantation
In plain words
The FDA reviewed every reported case. Ninety-four people went into liver failure. Of the acute cases, only eleven recovered without needing a new liver.
What was measured
Reported liver failure cases and proportion recovering without transplant
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Graham and colleagues at the FDA Office of Drug Safety abstracted all liver failure cases reported to the agency. Ninety-four cases were reported (89 acute, 5 chronic). Of the acute cases 58 (67%) were women and only 11 (13%) recovered without liver transplantation. The incidence of liver failure was elevated from the first month through at least the 26th month of use, so risk did not decline with continued exposure — it accumulated. Accounting for under-reporting, the estimated number needed to harm was between 600 and 1,500 patients treated for 26 months.
Written into the record, not signed off as a reviewed claim
Monthly liver monitoring could not have worked, and it was not being done anyway
In plain words
The plan for managing the risk was monthly blood tests. Nineteen patients went from normal liver function to irreversible injury inside a single month, and fewer than one user in twenty ever got the full test schedule.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Two findings, from the same FDA group, dismantle the risk-management strategy from both ends. Biologically: progression from normal hepatic function to irreversible liver injury occurred within one month in 19 patients, who were clinically indistinguishable from the 70 whose time course was unknown, leading the authors to cast doubt on the value of monthly aminotransferase monitoring as a means of prevention. Operationally: across four cohorts totalling 7,603 patients spanning April 1997 to September 1999, baseline testing rose from 15% before any FDA recommendation to 44.6% after four separate interventions, but follow-up testing after one month reached only 33.4% and fell to 13% by five months, and in every cohort fewer than 5% received all recommended tests by the third month. The conclusion was that FDA risk management efforts did not achieve meaningful or sustained improvement.
Written into the record, not signed off as a reviewed claim
Withdrawn in the UK within weeks; sold in the US for two and a half more years
In plain words
Britain pulled the drug within weeks of launching it. In the United States it went on to earn over two billion dollars before being withdrawn in March 2000.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Gale's contemporaneous account records the sequence: launched in the USA in March 1997, reached Europe later that year and was withdrawn within weeks on the grounds of liver toxicity, while generating sales of over US$2 billion in the USA and causing at least 90 cases of liver failure, 70 of which resulted in death or transplantation, before United States withdrawal in March 2000. His broader question about the class — how the glitazones achieved blockbuster status without clear evidence of advantage over existing therapy — was aimed at rosiglitazone and pioglitazone, and was answered seven years later by the rosiglitazone meta-analysis.
Written into the record, not signed off as a reviewed claim
The hepatotoxicity was inferred to be a class effect. It was not
In plain words
When troglitazone was pulled there was a reasonable fear that all drugs of its type would poison the liver. Two others in the same class have now been used for over twenty years without that signal.
What was measured
That fulminant hepatotoxicity is a property of PPAR-gamma agonism, rather than of troglitazone's chromanol substituent
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Troglitazone, pioglitazone and rosiglitazone share the thiazolidinedione head group and the PPAR-gamma target. Only troglitazone carries the alpha-tocopherol-derived chromanol tail, and only troglitazone produced fulminant hepatic failure at a measurable population rate. The distinction matters both ways: it means the receptor mechanism is not intrinsically hepatotoxic, and it means a shared pharmacological class tells you nothing reliable about a metabolic liability that arises from a substituent the other members do not have. The successor glitazones went on to fail for a different reason entirely — cardiovascular, in rosiglitazone's case — which is the same lesson from the other side.
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What is not here
5 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 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.
The first thiazolidinedione: it cut new-onset diabetes from 12.0 to 3.0 cases per 100 person-years in the Diabetes Prevention Program, and caused 94 reported cases of liver failure of which only 13% recovered without a transplant.
Recorded evidence blocks (8)
Q1
What did Troglitazone's largest trial (1499650 people) and its longest (3.2 years) measure?
1499650 people in Troglitazone's largest registered study, 3.2 years in its longest registered window, measuring rate of change of the right distal common carotid artery far wall intima-media thickness (IMT) measured every 6 months. ClinicalTrials.gov · 2026-09-01
3 na or unstated, 3 phase2, 1 phase3; NCT00116545; 2000-04; no ageing endpoint recorded. Last human test completed 2015, NCT02456428.
Interpretation These counts include studies where Troglitazone 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
na or unstated
3
phase2
3
phase3
1
Last recorded human testNCT02456428
2015-05
recorded 2026-09-01 · last checked 2026-09-04
Q2
From mouse to human: where has Troglitazone shown mechanism-only?
rate of change of the right distal common carotid artery far wall intima-media thickness (IMT) measured every 6 months — the recorded outcome words.
Show the evidence
mouse
mechanism-only
rat
mechanism-only
humanNCT00116545
mechanism-only; rate of change of the right distal common carotid artery far wall intima-media thickness (IMT) measured every 6 months; 6
recorded 2026-09-01 · last checked 2026-09-04
Q3
Could one person measure Troglitazone's effect on hospitalization for incident heart failure?
Hospitalization for incident heart failure: measured in Troglitazone's trials.
Interpretation hospitalization for incident heart failure is the recorded endpoint.
Show the evidence
biomarkers
hospitalization for incident heart failure; 2026-09-01
incident pancreatic cancer; 2026-09-01
hospitalization for acute pancreatitis; 2026-09-01
Not recorded for this substance
a recorded half-life; a small human trial reporting an effect
Q4
Which of hospitalization for acute pancreatitis, hospitalization for incident heart failure and incident pancreatic cancer did Troglitazone's trials measure?
hospitalization for acute pancreatitis, hospitalization for incident heart failure and incident pancreatic cancer lead 3 outcome terms across Troglitazone's trials. ClinicalTrials.gov · 2026-09-01
3 terms in all.
Show the evidence
hospitalization for incident heart failure
1
incident pancreatic cancer
1
hospitalization for acute pancreatitis
1
recorded 2026-09-01 · last checked 2026-09-04
Q5
Which 5 trials of Troglitazone posted no result?
Posted no result
5 of 5 completed trials
Registrations
NCT00003058, NCT00116545, NCT02475499, NCT02476760 and NCT02456428
Completion dates
oldest 2000-01; newest 2015-05
Show the evidence
Trial
NCT00003058
2000-01
NCT00116545
2000-04
NCT02475499
2015-04
NCT02476760
2015-04
NCT02456428
2015-05
Q6
At the median, Troglitazone's trials enrolled 443230 people — anything larger?
Median enrolment
443230
Largest enrolment
1499650
Registered trials counted
6
Q7
Was Troglitazone studied with fasting?
fasting is named in Troglitazone's label sentences: "Fasting glucose, insulin, and HbA(1c) were significantly lower in troglitazone- versus placebo-treated subjects (P < 0.01)." openfda-label+europepmc · 2006-07-01
1 recorded statement; fasting
Show the evidence
fasting
Fasting glucose, insulin, and HbA(1c) were significantly lower in troglitazone- versus placebo-treated subjects (P < 0.01).
recorded 2006-07-01 · last checked 2026-09-04
Q8
What is recorded about Troglitazone and autophagy?
"Troglitazone weakened PrP (106‑126)‑mediated neurotoxicity via PPARγ activation and autophagy flux inhibition." — where Troglitazone and autophagy appear together. Europe PMC · pathway abstract search · 2021-04-13
"Troglitazone weakened PrP (106‑126)‑mediated neurotoxicity via PPARγ activation and autophagy flux inhibition."
PMID 33846779
"In conclusion, the present study demonstrated that troglitazone protected primary neuronal cells against PrP (106‑126)‑induced neuronal cell death by inhibiting autophagic flux and activating PPARγ signals."
IGF-1PMID 28257428
"The PPARγ activator troglitazone increased IGF-1 gene expression and secretion in a dose dependent manner."
AMPK
PMID 28526426
"HepG2 cells were treated with troglitazone and phosphorylation of AMPK was found to increase at both Thr<sup>172</sup> and Ser<sup>485</sup> in a dose- and time-dependent manner."
PMID 28526426
"Treatment of HepG2 cells with insulin and PMA led to increases in p-AMPK Ser<sup>485</sup> via Akt and PKD1 respectively; however these kinases were not found to be implicated in increases seen from troglitazone."
autophagyPMID 28460464
"This indicates that troglitazone induced autophagy flux activation in human lung cancer cells."
AMPKPMID 24144566
"We synchronously detected the effects of troglitazone on insulin secretion and AMP-activated protein kinase (AMPK) activity under various conditions in isolated rat islets and MIN6 cells."
IGF-1PMID 16452250
"We report here that oral administration of thiazolidinediones (rosiglitazone and troglitazone) remarkably inhibited insulin-like growth factor-I (IGF-I)-promoted skin tumor development by 73% in BK5.IGF-1 transgenic mice, although they were previously found to be ineffective in inhibiting UV- or chemically induced mouse skin tumorigenesis."
mTOR
PMID 16452250
"The anti-IGF-I effect of troglitazone in mouse skin keratinocytes was due to, at least partially, inhibition of IGF-I-induced phosphorylation of p70S6 kinase (p70S6K) at Thr(389), a site specifically phosphorylated by mammalian target of rapamycin (mTOR)."
PMID 16452250
"Troglitazone did not directly inhibit mTOR kinase activity as shown by mTOR in vitro kinase assay but rapidly activated AMP-activated protein kinase (AMPK) through a yet undefined peroxisome proliferator-activated receptor gamma-independent mechanism."
sirtuinPMID 17954559
"It appears that many of the group 2 genes repressed by SIRT1 in mature adipocytes correspond to the same set of genes that are selectively activated by treatment of fat cells with the PPARgamma ligand, troglitazone."
mTORPMID 16825603
"Furthermore, cotreatment with rapamycin, a specific mTOR inhibitor, and troglitazone additively inhibited both p70S6K activity and protein synthesis, suggesting that the inhibitory effects of troglitazone are not mediated by mTOR."
NAD+PMID 20387640
"This is the first report demonstrating that troglitazone and alpha-tocopherol C6, unlike a-tocopherol and pioglitazone substantially inhibited the activity of NAD(P)H:quinone oxidoreductase (DT-diaphorase) and this effect is increased with specific DT-diaphorase inhibitor, dicoumarol."
recorded 2021-04-13 · 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
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