This page shows what was measured, who it was measured in, and what that does not settle.
What Pioglitazone does in the body
Type 2 diabetes — a tablet that makes the body respond to its own insulin
Fat cells decide what to do with fat by switching genes on and off, and a protein inside their nucleus makes that decision. Pioglitazone binds that protein and changes the decision: store fat in fat, not in liver and muscle. Once fat leaves the liver and muscle, the insulin the body already makes starts working again. Because the drug works by changing gene transcription rather than by blocking something, it takes weeks to show its full effect — and the same protein in the kidney tells the body to hold on to salt and water, which is where the swelling and the heart failure risk come from.
What happened in people
A hazard ratio of 0.84 (95% CI 0.72 to 0.98, p=0.027) on the main secondary composite of death, non-fatal myocardial infarction and stroke in the same trial
✎ 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 only thiazolidinedione in routine use in the United States, and the only oral diabetes drug that measurably clears fat from the liver
Where it acts
Nuclei of adipocytes, skeletal muscle and hepatocytes; and the collecting duct of the kidney, where the same receptor drives the fluid retention
Kind of result
Living longer, or avoiding a major event
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
24 registered substances share the start of this name, which is why a search for it can return more than one thing.
FDA substance registry · RX5TJ6429Q · 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 154 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.
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.
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.
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 was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Blood sugar
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
△Only a number moved11 registered test measure.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Focus
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Body weight
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
△Only a number moved1 registered test measure.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Cholesterol
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
△Only a number moved1 registered test measure.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Blood sugar
hba1c at week 24; hba1c; hba1c after 24 weeks; hba1c from baseline to week 24; hba1c at 52 weeks; endogenous glucose production; glucose rates of disappearance; aim 2 acute insulin resistance to intravenous glucose
Focus
verbal memory; selective attention
Body weight
body weight
Cholesterol
fasting triglyceride level
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
△ Only a number moved
11 registered test measure.
— Not recorded
Harms were not a registered measure for this goal.
… Waiting for a reviewer
Who was studied is listed further down the page.
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.
Composite of all-cause mortality, non-fatal myocardial infarction including silent infarction, stroke, acute coronary syndrome, coronary or leg-artery intervention, and above-ankle amputation
✗ The study did not show it
Who was studied
PROactive (NCT00174993)
How many people
5238
Study design
Prospective randomised double-blind placebo-controlled outcome trial, average 34.5 months
Compared against
A dummy treatment
Kind of result
Living longer, or avoiding a major event
What was found
Hazard ratio 0.90 (95% CI 0.80 to 1.02, P = 0.095) — primary endpoint not met. Main secondary endpoint hazard ratio 0.84 (95% CI 0.72 to 0.98, P = 0.027)
Repeated elsewhere
Partially Replicated
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. Hospital admission for heart failure occurred in 149 patients on pioglitazone against 108 on placebo (6% against 4%), though heart-failure mortality did not differ. The drug is generally cited for the secondary endpoint, not for the endpoint it was designed around.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, once daily, in 15 mg, 30 mg and 45 mg strengths
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Fatal or non-fatal stroke or myocardial infarction in patients without diabetes with recent ischaemic stroke or TIA and HOMA-IR above 3.0
✓ The study showed what it set out to show
Who was studied
IRIS — Insulin Resistance Intervention after Stroke
How many people
3876
Study design
Multicentre randomised double-blind placebo-controlled trial, 4.8 years
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
P = 0.007; hazard ratio 0.76 (95% CI 0.62 to 0.93). New-onset diabetes hazard ratio 0.48 (95% CI 0.33 to 0.69, P < 0.001)
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. All-cause mortality did not differ (HR 0.93, 95% CI 0.73 to 1.17, P = 0.52). Weight gain above 4.5 kg occurred in 52.2% against 33.7%, oedema in 35.6% against 24.9%, and fracture requiring surgery or hospitalisation in 5.1% against 3.2% (P = 0.003).
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, once daily, in 15 mg, 30 mg and 45 mg strengths
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Improvement in histological features of non-alcoholic steatohepatitis, composite of steatosis, lobular inflammation, hepatocellular ballooning and fibrosis scores
✗ The study did not show it
Who was studied
PIVENS (NCT00063622)
How many people
247
Study design
Randomised double-blind placebo-controlled trial with paired liver biopsies, 96 weeks
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Pioglitazone 34% against placebo 19%, P = 0.04 against a prespecified significance threshold of 0.025 — not met. Vitamin E 43% against 19%, P = 0.001 — met
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. Neither agent improved fibrosis scores (P = 0.12 for pioglitazone). Subjects receiving pioglitazone gained more weight than either other group.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, once daily, in 15 mg, 30 mg and 45 mg strengths
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Incident bladder cancer associated with ever use, duration, cumulative dose and time since initiation of pioglitazone
✗ The study did not show it
Who was studied
Lewis 2015 Kaiser Permanente Northern California bladder cancer cohort
How many people
193099
Study design
Population cohort with nested case-control analysis, 1997 to December 2012
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Adjusted hazard ratio 1.06 (95% CI 0.89 to 1.26) for ever use — no significant association; nested case-control adjusted odds ratio 1.18 (95% CI 0.78 to 1.80)
Repeated elsewhere
Failed to Replicate
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. In a parallel cohort of 236,507 persons examining ten other cancers, ever use was associated with prostate cancer (HR 1.13, 95% CI 1.02 to 1.26) and pancreatic cancer (HR 1.41, 95% CI 1.16 to 1.71). The authors state an increased bladder cancer risk still could not be excluded.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, once daily, in 15 mg, 30 mg and 45 mg strengths
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 4 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.20 registered measures 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.
■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.
Where a source records it acting
Liver: Decreases insulin resistance in the periphery and in the liver, resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output
US prescribing information · 0331400c-b163-4856-bfb0-965470247cb3 · read 2026-08-27
Muscle: Agonist for PPAR-gamma receptors found in tissues important for insulin action such as adipose tissue, skeletal muscle, and liver
US prescribing information · 0331400c-b163-4856-bfb0-965470247cb3 · read 2026-08-27
Start
Pioglitazone
What a person takes: Oral tablet, once daily, in 15 mg, 30 mg and 45 mg strengths.
The measurement behind this step
A conventional immediate-release tablet of the hydrochloride salt. The clinically important property is not the formulation but the time course: because the drug acts through gene transcription and adipose tissue remodelling, the full glycaemic effect takes weeks to appear and persists for weeks after stopping. The label states the antihyperglycaemic effect occurs only in the presence of endogenous insulin.
Getting in
Absorbed and carried into the cell nucleus
The tablet is absorbed and the drug moves into cells, and then into their nuclei — the compartment where genes are read. That is unusual: most drugs act on the cell surface.
╌╌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
Pioglitazone is a lipophilic thiazolidinedione that crosses membranes passively and enters the nucleus. It is metabolised largely by CYP2C8 and, to a lesser extent, CYP3A4, and several of its metabolites are pharmacologically active, which is why the effect outlasts the parent compound.
Inside the nucleus sits a protein whose job is to sit on DNA and decide whether nearby genes get read. The drug slots into a pocket in that protein and changes its shape.
╌╌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
PPAR-gamma is a ligand-activated nuclear receptor. The thiazolidinedione head hydrogen-bonds within the ligand-binding pocket, stabilising helix 12 of the activation function 2 surface. The label states that PPAR receptors are found in tissues important for insulin action — adipose tissue, skeletal muscle and liver.
The changed switch pairs up and rewrites which genes get read
The reshaped protein pairs with a partner, sits down on specific stretches of DNA, and recruits the machinery that turns genes on. Dozens of genes controlling how fat is handled change their output.
╌╌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
Ligand binding releases corepressors and recruits coactivators. PPAR-gamma heterodimerises with the retinoid X receptor and binds PPAR response elements, modulating transcription of insulin-responsive genes controlling glucose and lipid metabolism — adiponectin, lipoprotein lipase, fatty acid transporters and GLUT4 among them.
Fat is redirected out of liver and muscle and back into fat tissue
Fat cells become better at their job of storing fat, so fat stops accumulating in the liver and in muscle. Those are the tissues where fat interferes with insulin working.
╌╌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
Subcutaneous adipocytes proliferate and increase triglyceride storage capacity while adiponectin secretion rises; ectopic lipid in hepatocytes and myocytes falls, restoring insulin signalling in both. In PIVENS, hepatic steatosis improved significantly against placebo (p<0.001) — the mechanism visible directly on biopsy.
Circulating insulin starts working again — over weeks, not hours
The insulin the body already makes becomes more effective, so blood sugar and insulin levels both fall. This takes weeks, because the drug works by changing which proteins the cell makes.
──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
The label states that decreased insulin resistance produces lower plasma glucose, lower plasma insulin and lower HbA1c, that pioglitazone is not an insulin secretagogue, and that it does not lower glucose in models lacking endogenous insulin. Triglycerides fall and HDL cholesterol rises, with no consistent change in LDL or total cholesterol.
The same receptor in the kidney holds on to salt and water
The gene switch this drug flips is not only in fat. In the kidney it tells the body to keep sodium, which means keeping water. That is why ankles swell and why the drug can tip a weak heart into failure.
──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
PPAR-gamma activation in the renal collecting duct increases epithelial sodium channel-mediated sodium reabsorption and plasma volume expansion. The label describes the fluid retention as dose-related and most common in combination with insulin. In IRIS oedema occurred in 35.6% against 24.9% on placebo; in PROactive, 149 pioglitazone patients against 108 on placebo were hospitalised for heart failure.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 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.
hba1c at week 24
hemoglobin a1c at week 24
hba1c
hba1c after 24 weeks
hba1c from baseline to week 24
hba1c at 52 weeks
endogenous glucose production
glucose rates of disappearance
aim 2 acute insulin resistance to intravenous glucose
plasma beta amyloid levels
and 10 more.
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.
Names that fit none of the three (20)
overall response
virologic response
aim 1 apnea hypopnea index
time till the first cardiovascular composite endpoint
verbal memory
selective attention
beta amyloid in spinal fluid
carotid intima media thickness
nominal change from baseline in atheroma volume
adverse events
physical examination
hypoglycemic events
electrocardiogram
vital signs
liver histology
beta cell function c peptide auc
reduction in conversion of igt to diabetes
intima media thickness of carotid artery
sputum neutrophil
fat after 16 weeks treatment using a hologic qdr 4500 dexa
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
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. three to seven hours hours
Read from the label, which states: “The mean serum half-life (t 1/2 ) of pioglitazone and its metabolites (M-III and M-IV) range from three to seven hours and 16 to 24 hours, respectively.”
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 type 2 diabetes and marked insulin resistance, usually after metformin. Use collapsed after 2011 when a bladder cancer restriction was added, and has partly recovered since the definitive cohort study reported.
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.
Who a named study recorded including and excluding
NCT00174993 recorded its participants as: Ages eligible for study: 35 to 75 years, all sexes, as registered.
ClinicalTrials.gov record · NCT00174993 · read 2026-08-28
It included: Type 2 diabetes mellitus; Glycosylated hemoglobin above the upper limit of normal; Established history of macrovascular disease, defined as 1 or more of: myocardial infarction at least 6 months before entry into the study; stroke at least 6 months before entry into the study; percutaneous coronary intervention or coronary artery bypass graft at least 6 months before entry into the study; acute coronary syndrome at least 3 months before entry into the study; objective evidence of coronary artery disease; peripheral arterial obstructive disease.
ClinicalTrials.gov record · NCT00174993 · read 2026-08-28
It excluded: Signs of type 1 diabetes; Myocardial infarction, stroke, coronary artery bypass graft, or percutaneous cardiac intervention in the 6 months prior to enrolment; Acute coronary syndrome in the 3 months prior to enrolment; Heart failure at entry defined as patient having a New York Heart Association functional score of II or above; Significantly impaired hepatic function, defined as alanine aminotransferase greater than 2.5 times the upper limit of normal; Required dialysis.
ClinicalTrials.gov record · NCT00174993 · read 2026-08-28
What the label states about particular groups
On pediatric, the label states: “Safety and effectiveness of pioglitazone hydrochloride in pediatric patients have not been established.”
US prescribing information · fbdaaa34-06c4-49af-85b4-91a85922b30b · read 2026-08-30
On older people, the label states: “A total of 92 patients (15.2%) treated with pioglitazone hydrochloride in the three pooled 16 to 26 week double-blind, placebo-controlled, monotherapy trials were ≥ 65 years old and two patients (0.3%) were ≥ 75 years old.”
US prescribing information · fbdaaa34-06c4-49af-85b4-91a85922b30b · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Limited data with pioglitazone in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage.”
US prescribing information · fbdaaa34-06c4-49af-85b4-91a85922b30b · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There is no information regarding the presence of pioglitazone in human milk, the effects on the breastfed infant, or the effects on milk production.”
US prescribing information · fbdaaa34-06c4-49af-85b4-91a85922b30b · read 2026-08-30
Where the result stopped carrying
PROactive missed the primary composite endpoint it was designed and powered around, and the drug is remembered for the secondary one
Hospital admissions for heart failure rose from 4% to 6% in PROactive, producing the boxed warning the drug still carries
PIVENS did not meet its prespecified significance threshold in non-alcoholic steatohepatitis, in a trial where vitamin E did
The 2011 bladder cancer signal drove regulatory restriction and a collapse in prescribing that a decade of follow-up in 193,099 people did not confirm
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
Prescription only
❝ 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, in 15 mg, 30 mg and 45 mg strengths
✎ 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
A conventional immediate-release tablet of the hydrochloride salt.
✎ 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. The rest of the recorded wording: The clinically important property is not the formulation but the time course: because the drug acts through gene transcription and adipose tissue remodelling, the full glycaemic effect takes weeks to appear and persists for weeks after stopping. The label states the antihyperglycaemic effect occurs only in the presence of endogenous insulin.
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
A boxed warning states that thiazolidinediones including pioglitazone cause or exacerbate congestive heart failure in some patients; the drug is not recommended in symptomatic heart failure and is contraindicated in NYHA class III or IV. Dose-related oedema occurs and is most common in combination with insulin. Fractures are increased, particularly in female patients. Bladder cancer is listed under warnings and precautions with advice not to use in active bladder cancer and caution with prior history. Postmarketing reports include hepatic failure, sometimes fatal, and macular oedema. Hypoglycaemia is not caused by pioglitazone alone but can occur when it is combined with insulin or an insulin secretagogue. The label states there have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with pioglitazone.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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.
Pioglitazone appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 2688 reaction mentions were counted. One report can name several reactions.
open-targets-adr · recorded 2026-06-24 · 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, once daily, in 15 mg, 30 mg and 45 mg strengths
✎ 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
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: The clinically important property is not the formulation but the time course: because the drug acts through gene transcription and adipose tissue remodelling, the full glycaemic effect takes weeks to appear and persists for weeks after stopping. The label states the antihyperglycaemic effect occurs only in the presence of endogenous insulin.
No source is stored against this line.
What is recorded as being sold
134 products list this as an active ingredient in the United States drug directory. 91 of them contain it and nothing else.
FDA National Drug Code directory · 71610-495 · read 2026-08-29
They are sold as powder, tablet and tablet, film coated, taken oral.
FDA National Drug Code directory · 71610-495 · read 2026-08-29
The regulator's established pharmacologic class for it is ppar alpha [cs], ppar gamma [cs] and peroxisome proliferator receptor alpha agonist [epc].
FDA National Drug Code directory · 71610-495 · read 2026-08-29
54 published labels name it as an active ingredient. 41 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · a7e8d5a3-b0da-1d70-e053-2a95a90aa435 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · a7e8d5a3-b0da-1d70-e053-2a95a90aa435 · read 2026-08-29
Pioglitazone Hydrochloride is tablets at Tablets: 15 mg, 30 mg, and 45 mg, recorded as prescription product; fda label in effect 2025-05-17 in the United States.
US prescribing information · 0331400c-b163-4856-bfb0-965470247cb3 · read 2026-08-27
Recorded price in US: 0.0647–0.11115 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 55 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
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 Pioglitazone 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 PROactive demonstrated a macrovascular benefit — the primary endpoint returned p=0.095, and the label states there is no conclusive evidence of macrovascular risk reduction with pioglitazone
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 IRIS result transfers to people with type 2 diabetes — IRIS enrolled patients who did not have diabetes, selected on a HOMA-IR score above 3.0 after a stroke
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 bladder cancer question is closed — the definitive cohort found no significant association and its authors state an increased risk could not be excluded, while the label warning remains
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 pioglitazone treats fatty liver disease — it missed the prespecified primary histological endpoint in PIVENS and improved no fibrosis score
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.
Formulation uncertainty
Several salts, forms or products of Pioglitazone 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.
PROactive missed its primary endpoint and is remembered for its secondary one
In plain words
The trial that was supposed to prove pioglitazone prevents cardiovascular events enrolled 5,238 people with type 2 diabetes and existing vascular disease. On the endpoint it had declared in advance, the result was not statistically significant. On a narrower endpoint declared as secondary, it was.
What was measured
Hazard ratios for the prespecified primary composite endpoint and the main secondary composite endpoint over an average 34.5 months in 5,238 patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
PROactive randomised 5,238 patients with type 2 diabetes and evidence of macrovascular disease to pioglitazone titrated from 15 mg to 45 mg (n=2,605) or matching placebo (n=2,633), on top of existing therapy, and observed them an average of 34.5 months. The prespecified primary endpoint was a composite of all-cause mortality, non-fatal myocardial infarction including silent infarction, stroke, acute coronary syndrome, endovascular or surgical intervention in the coronary or leg arteries, and above-ankle amputation. It occurred in 514 of 2,605 on pioglitazone and 572 of 2,633 on placebo: hazard ratio 0.90 (95% CI 0.80 to 1.02, p=0.095). The main secondary endpoint — the narrower composite of all-cause mortality, non-fatal myocardial infarction and stroke — occurred in 301 against 358 patients: hazard ratio 0.84 (95% CI 0.72 to 0.98, p=0.027). The published interpretation states that pioglitazone reduces the secondary composite. It does not claim the primary was met, because it was not.
Written into the record, not signed off as a reviewed claim
In the same trial it put half as many people again into hospital with heart failure
In plain words
Alongside the cardiovascular result, PROactive counted admissions for heart failure. There were 149 in the pioglitazone group and 108 on placebo — 6% against 4%. This finding is the reason the drug carries a boxed warning.
What was measured
Hospital admissions for heart failure by arm in a 5,238-patient randomised trial, and the resulting boxed warning text
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
In PROactive, 149 patients in the pioglitazone group and 108 in the placebo group were admitted to hospital with heart failure, 6% against 4%; mortality from heart failure did not differ between the groups. The United States label carries a boxed warning stating that thiazolidinediones including pioglitazone cause or exacerbate congestive heart failure in some patients, that patients must be monitored after initiation and after dose increases for excessive rapid weight gain, dyspnoea and oedema, that the drug is not recommended in symptomatic heart failure, and that initiation in established New York Heart Association class III or IV heart failure is contraindicated. The mechanism is not idiosyncratic: PPAR-gamma activation in the renal collecting duct promotes sodium reabsorption, and the label describes the fluid retention as dose-related and most common in combination with insulin.
Written into the record, not signed off as a reviewed claim
IRIS found a 24% reduction in stroke and heart attack — in people without diabetes
In plain words
A different trial gave pioglitazone to 3,876 people who had recently had a stroke or mini-stroke, were insulin resistant, and did not have diabetes. Over almost five years, strokes and heart attacks fell from 11.8% to 9.0%, and new diabetes fell by half.
What was measured
Hazard ratios for fatal or non-fatal stroke or myocardial infarction, new-onset diabetes and all-cause mortality by 4.8 years in 3,876 non-diabetic patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
IRIS (Insulin Resistance Intervention after Stroke) was a multicentre double-blind trial randomising 3,876 patients with a recent ischaemic stroke or transient ischaemic attack, without diabetes, and with a HOMA-IR score above 3.0, to pioglitazone at a target dose of 45 mg daily or placebo. The primary outcome — fatal or non-fatal stroke or myocardial infarction — occurred by 4.8 years in 175 of 1,939 (9.0%) on pioglitazone and 228 of 1,937 (11.8%) on placebo: hazard ratio 0.76 (95% CI 0.62 to 0.93, p=0.007). New-onset diabetes occurred in 73 (3.8%) against 149 (7.7%): hazard ratio 0.48 (95% CI 0.33 to 0.69, p<0.001). All-cause mortality did not differ: hazard ratio 0.93 (95% CI 0.73 to 1.17, p=0.52). This is the only trial in which pioglitazone met its own prespecified primary endpoint, and it was run in a population without the disease the drug is licensed for.
Written into the record, not signed off as a reviewed claim
The same trial measured what it cost: weight, oedema and fractures
In plain words
IRIS reported the harms alongside the benefit. Over half the pioglitazone group gained more than 4.5 kg, a third developed swelling, and fractures serious enough to need surgery or hospital admission rose from 3.2% to 5.1%.
What was measured
Proportions with weight gain above 4.5 kg, oedema and fracture requiring surgery or hospitalisation, by arm, over 4.8 years
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
In IRIS, weight gain exceeding 4.5 kg occurred in 52.2% of the pioglitazone group against 33.7% on placebo (p<0.001); oedema in 35.6% against 24.9% (p<0.001); and bone fracture requiring surgery or hospitalisation in 5.1% against 3.2% (p=0.003). The fracture signal is a class effect of thiazolidinediones with a mechanistic explanation: PPAR-gamma activation drives mesenchymal stem cells toward adipocyte rather than osteoblast lineage, reducing bone formation. The United States label lists fractures among warnings and precautions, noting an increased incidence in female patients and advising that current standards of care for bone health be applied. Set against the primary result, the arithmetic is that treating for 4.8 years avoided about 2.8 strokes or heart attacks per 100 patients and caused about 1.9 additional serious fractures per 100.
Written into the record, not signed off as a reviewed claim
The bladder cancer restriction of 2011 was not supported by the definitive cohort
In plain words
An interim analysis in 2011 suggested pioglitazone raised bladder cancer risk. France and Germany suspended it, the FDA added a warning, and prescribing collapsed. When the same cohort was followed for a decade and fully analysed, there was no significant association.
What was measured
Adjusted hazard ratio for bladder cancer with ever use of pioglitazone in 193,099 persons over up to fifteen years, with matched case-control confirmation
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Lewis and colleagues followed 193,099 people aged 40 or over in the Kaiser Permanente Northern California cohort from 1997-2002 until December 2012, of whom 34,181 (18%) received pioglitazone for a median 2.8 years (range 0.2 to 13.2), with 1,261 incident bladder cancers. Crude incidence was 89.8 per 100,000 person-years in users and 75.9 in non-users. Ever use of pioglitazone was not associated with bladder cancer risk: adjusted hazard ratio 1.06 (95% CI 0.89 to 1.26). A nested case-control analysis of 464 cases and 464 matched controls agreed, adjusted odds ratio 1.18 (95% CI 0.78 to 1.80). No clear pattern of risk appeared for time since initiation, duration or cumulative dose. In a parallel cohort of 236,507 people examining ten further cancers, eight showed no association, while ever use was associated with prostate cancer (HR 1.13, 95% CI 1.02 to 1.26) and pancreatic cancer (HR 1.41, 95% CI 1.16 to 1.71), which the authors state merit further investigation as to whether they are causal or reflect chance, residual confounding or reverse causality. The authors are explicit that an increased bladder cancer risk could not be excluded. The current United States label still lists bladder cancer under warnings and precautions and advises against use in active bladder cancer.
Written into the record, not signed off as a reviewed claim
In fatty liver disease it missed the primary endpoint that vitamin E met
In plain words
A trial of 247 adults with fatty liver inflammation and no diabetes compared pioglitazone, vitamin E and placebo over almost two years, with liver biopsies at both ends. Vitamin E met the prespecified threshold. Pioglitazone did not, though it improved several individual measurements.
What was measured
Proportion with histological improvement in non-alcoholic steatohepatitis at 96 weeks against a prespecified significance threshold of 0.025, with secondary biochemical and histological components
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
PIVENS randomised 247 adults with non-alcoholic steatohepatitis and without diabetes to pioglitazone 30 mg daily (n=80), vitamin E 800 IU daily (n=84) or placebo (n=83) for 96 weeks. Because two primary comparisons were planned, p values below 0.025 were prespecified as significant. Vitamin E improved histology in 43% against 19% on placebo (p=0.001); pioglitazone improved histology in 34% against 19% (p=0.04), which does not meet the threshold. Both agents reduced alanine and aspartate aminotransferase against placebo (p<0.001 for both), hepatic steatosis (p=0.005 vitamin E, p<0.001 pioglitazone) and lobular inflammation (p=0.02 and p=0.004), but neither improved fibrosis scores (p=0.24 and p=0.12). Subjects on pioglitazone gained more weight than either other group. The authors state there was no benefit of pioglitazone over placebo for the primary outcome, with significant benefits on some secondary outcomes.
This order is fixed in code and does not count clicks or time on the page.
What is not here
3 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 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 nuclear receptor agonist that reprograms fat cells to restore insulin sensitivity rather than forcing insulin release — which missed its primary composite endpoint in a 5,238-patient cardiovascular outcome trial (HR 0.90, 95% CI 0.80 to 1.02, p=0.095) while hitting the secondary one (HR 0.84, 95% CI 0.72 to 0.98, p=0.027), reduced stroke and heart attack by 24% in 3,876 non-diabetic patients after a stroke, and does all of this at the cost of oedema, weight gain, fractures and a boxed warning for congestive heart failure.
Recorded evidence blocks (16)
Q1
What did Pioglitazone's largest trial (1499650 people) and its longest (18 years) measure?
1499650 people in Pioglitazone's largest registered study, 18 years in its longest registered window, measuring Time to the Composite of All Cause Mortality, Non-Fatal Myocardial Infarction, Stroke, Acute Coronary Syndrome, Major Leg Amputation, Cardiac Intervention, Bypass Surgery or Leg Revascularization. ClinicalTrials.gov · 2026-09-01
111 phase2, 105 phase4, 84 phase3, 52 phase1, 42 na, 16 na or unstated, 11 early phase1; NCT02958956; 2015-05-29. Last human test completed 2026, NCT07444424.
Interpretation These counts include studies where Pioglitazone 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
phase2
111
phase4
105
phase3
84
phase1
52
na
42
na or unstated
16
2 more recorded rows
early phase1
11
Last recorded human testNCT07444424
2026-07-02
recorded 2026-09-01 · last checked 2026-09-04
Q2
From mouse to human: where has Pioglitazone shown lifespan?
Interpretation Time to the Composite of All Cause Mortality, Non-Fatal Myocardial Infarction, Stroke, Acute Coronary Syndrome, Major Leg Amputation, Cardiac Intervention,… — the recorded outcome words.
Show the evidence
mouse
lifespan
rat
mechanism-only
humanNCT00174993
lifespan; Time to the Composite of All Cause Mortality, Non-Fatal Myocardial Infarction, Stroke, Acute Coronary Syndrome, Major Leg Amputation, Cardiac Intervention, Bypass Surgery or Leg Revascularization.; 403
"inclusion was finished"; 58 of 403 registered studies
Show the evidence
Trial
NCT00159211
terminated; "inclusion was finished"
NCT00203996
terminated; "Did not meet target patient accrual goals"
NCT00212004
terminated; "Limited budget to continue this study"
NCT00226330
terminated; "The development program has been terminated"
NCT00229684
terminated; "The development program has been terminated"
NCT00232362
withdrawn; "This study was not conducted as the Principal Investigator left the institution"
14 further recorded trials
NCT00306826
withdrawn; "financial support withdrawn"
NCT00368017
terminated; "unable to replace Fellow conducting the study who left institution in 2007"
NCT00376181
terminated; "Combination formulation concerns"
NCT00411892
terminated; "See termination reason in detailed description"
NCT00437970
withdrawn; "Unable to secure supply of the study medication"
NCT00521820
terminated; "Higher incidence of hospitalization for congestive heart failure in pioglitazone-treated subjects compared to glyburide treated subjects."
NCT00571519
terminated; "DSPD focusing on Study 301 to confirm the clinical profile before proceeding. Daiichi Sankyo Pharma Development terminated this study on 23 Apr 2008 because of changes in the clinical development plan with 94 of 2600 planned, randomized…"
NCT00586261
terminated; "Low enrollment because of the specifics of the inclusion criteria"
NCT00690118
terminated; "The interim analysis showed no tendency in favour of the verum group. Therefore it was decided to stop the study prematurely."
NCT00722917
terminated; "Animal Toxicity Findings"
NCT00742326
terminated; "Enrollment stopped prior to complete enrollment due to slow accrual"
NCT00743327
terminated; "No Participants completed study"
NCT00775164
withdrawn; "Inadequate enrollment"
NCT00787644
terminated; "new safety concerns which emerged about pioglitazone during the trial"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Pioglitazone used Pioglitazone 45 mg PO QD — over how long?
More Pioglitazone was worse in human: at what point?
Hormetic in human: "Hormetic-biphasic dose response relationships are reported herein for human endothelial progenitor cells involving estradiol, nicotine, the anti-diabetic agent pioglitazone, resveratrol, and progesterone." Europe PMC · dose-response search · 2022-05-24
5 recorded sentences naming Pioglitazone; Hormetic, U-shaped, dose-response
Show the evidence
HormeticPMID 35221821
"Hormetic-biphasic dose response relationships are reported herein for human endothelial progenitor cells involving estradiol, nicotine, the anti-diabetic agent pioglitazone, resveratrol, and progesterone."
U-shapedPMID 31548602
"It seems that pioglitazone protects the injured rat kidney in a U-shaped manner."
dose-response
PMID 35741327
"To achieve this, a pioglitazone dose-response assay was determined over a range varying from 0 to 10 µM."
PMID 28025963
"Pooled results derived from a random-effects model, and the dose-response analyses were conducted for the association between cumulative dose or duration of pioglitazone use and BC risk."
PMID 28912917
"To find out the efficacy and safety of the low-dose (7.5 mg/day) pioglitazone therapy, we reviewed the dose-response of pioglitazone on favorable effects and adverse effects due to pioglitazone, by searching the reports on effects of daily dose of 7.5 mg and/or 15 mg and/or 30 mg of pioglitazone."
recorded 2022-05-24 · last checked 2026-09-04
Q6
Pioglitazone's half-life is three to seven hours — which schedules were studied?
three to seven hours, the half-life Pioglitazone's label states. openfda-label · 060e3169-46a7-419d-9acc-05586cb2406b · 2026-08-27
Show the evidence
half life
three to seven hours hours; The mean serum half-life (t 1/2 ) of pioglitazone and its metabolites (M-III and M-IV) range from three to seven hours and 16 to 24 hours, respectively.
tmax
Absorption Following oral administration of pioglitazone, T max of pioglitazone was within two hours.
metabolism
Metabolism Pioglitazone is extensively metabolized by hydroxylation and oxidation; the metabolites also partly convert to glucuronide or sulfate conjugates.
recorded 2026-08-27 · last checked 2026-09-04
Q7
Could one person measure Pioglitazone's effect on hba1c at week 24?
Hba1c at week 24: measured in Pioglitazone's trials.
hba1c at week 24 is the recorded endpoint.
Show the evidence
biomarkers
hba1c at week 24; 2026-09-01
hemoglobin a1c at week 24; 2026-09-01
hba1c; 2026-09-01
overall response; 2026-09-01
hba1c after 24 weeks; 2026-09-01
hba1c from baseline to week 24; 2026-09-01
14 more recorded rows
biomarkers
hba1c at 52 weeks; 2026-09-01
biomarkers
endogenous glucose production; 2026-09-01
biomarkers
glucose rates of disappearance; 2026-09-01
biomarkers
virologic response; 2026-09-01
biomarkers
aim 1 apnea hypopnea index; 2026-09-01
biomarkers
aim 2 acute insulin resistance to intravenous glucose; 2026-09-01
biomarkers
time till the first cardiovascular composite endpoint; 2026-09-01
biomarkers
verbal memory; 2026-09-01
biomarkers
selective attention; 2026-09-01
biomarkers
plasma beta amyloid levels; 2026-09-01
biomarkers
cerebral glucose metabolism; 2026-09-01
biomarkers
inflammatory markers in spinal fluid; 2026-09-01
biomarkers
beta amyloid in spinal fluid; 2026-09-01
biomarkers
carotid intima media thickness; 2026-09-01
half life
2026-09-04; halfLife; hours; three to seven hours; 2026-08-27
human trials at or under30
133
smallest human trial
0; NCT00232362; PHASE1; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; WITHDRAWN
Q8
Which of adverse events, aim 1 apnea hypopnea index and aim 2 acute insulin resistance to intravenous glucose did Pioglitazone's trials measure?
adverse events, aim 1 apnea hypopnea index and aim 2 acute insulin resistance to intravenous glucose lead 40 outcome terms across Pioglitazone's trials. ClinicalTrials.gov · 2026-09-01
overall response, hba1c after 24 weeks, hba1c from baseline to week 24, hba1c at 52 weeks, endogenous glucose production and glucose rates of disappearance follow.
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hba1c at week 24
1
hemoglobin a1c at week 24
1
hba1c
1
overall response
1
hba1c after 24 weeks
1
hba1c from baseline to week 24
1
14 more recorded rows
hba1c at 52 weeks
1
endogenous glucose production
1
glucose rates of disappearance
1
virologic response
1
aim 1 apnea hypopnea index
1
aim 2 acute insulin resistance to intravenous glucose
1
time till the first cardiovascular composite endpoint
1
verbal memory
1
selective attention
1
plasma beta amyloid levels
1
cerebral glucose metabolism
1
inflammatory markers in spinal fluid
1
beta amyloid in spinal fluid
1
carotid intima media thickness
1
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which of Pioglitazone's 29 ongoing trials reports first?
Maximum Observed Plasma Concentration (Cmax); Determination of the variability of HbA1c (by measurement of standard deviation of HbA1c) between the 2 diabetes treatment thresholds; latest 2032-12-31
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Trial
NCT02592317
"A Study to Evaluate the Effect of Multiple Doses of JNJ-56021927 on the Pharmacokinetics of Multiple Cytochrome P450 and Transporter Substrates in Participants With Castration-Resistant Prostate Cancer"; n 23; "Maximum Observed Plasma Concentration (Cmax)"; 2027-12-31
NCT02879409
"HbA1c Variability in Type II Diabetes"; n 150; "Determination of the variability of HbA1c (by measurement of standard deviation of HbA1c) between the 2 diabetes treatment thresholds"; 2026-10-01
NCT02969798
"Pre-diabetes in Subject With Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)"; n 700; "Beta cell function"; 2027-07
NCT03109288
"Targeting Residual Activity By Precision, Biomarker-Guided Combination Therapies of Multiple Sclerosis (TRAP-MS)"; n 250; "Primary outcome will be change in CombiWISE progression rate at the end of monotherapy plus combination therapy period in comparison to projected baseline disability progression."; 2029-01-01
NCT03866408
"Insulin Regulation of Lipolysis and Lipolysis Proteins"; n 64; "Adipocyte response to insulin - perilipin 1 and FSP27 relative to HSL and ATGL"; 2026-12-31
NCT03878459
"Dapagliflozin Plus Pioglitazone in T1DM"; n 120; "Decrease in HbA1c"; 2027-12-31
14 further recorded trials
NCT04501406
"Low-Dose Pioglitazone in Patients With NASH (AIM 2)"; n 166; "The proportion of pioglitazone-treated patients relative to placebo achieving an improvement of ≥2 points in non-alcoholic fatty liver disease activity score (NAS) without an increase in fibrosis stage."; 2027-08-31
NCT05013255
"Pioglitazone Therapy Targeting Fatigue in Breast Cancer"; n 30; "Muscle Gene Expression"; 2026-12
NCT05028140
"Efficacy and Safety of Piemonte Association in the Treatment of Type II Diabetes Mellitus"; n 480; "Glycated hemoglobin"; 2027-09
NCT05305287
"Quantifying Hepatic Mitochondrial Fluxes in Humans"; n 60; "Effect of pioglitazone on hepatic mitochondrial TCA cycle fluxes"; 2027-03-31
NCT05501483
"Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes"; n 60; "Changes in fat cell lipolysis after 6 months of treatment"; 2032-12-31
NCT05753657
"A Pilot Study of Monitoring Insulin Levels and Treating Hyperinsulinemia and Hyperglycemia With Pioglitazone in Patients Treated With Alpelisib for Metastatic Breast Cancer."; n 30; "Rate of severe (grade 3 and 4) hyperglycemia in patients enrolled in the study and in patients treated per protocol"; 2027-12-31
NCT05838287
"Pioglitazone on Heart Failure in Type-2 Diabetes Mellitus Participants"; n 78; "Change in Systolic function"; 2030-01
NCT05919147
"The Neuroendocrine Effects of Pioglitazone in Patients With Cancer and Cachexia"; n 24; "Change in skeletal muscle insulin sensitivity"; 2026-06-30
NCT05946564
"A Trial to Evaluate the Efficacy of Pioglitazone to Promote Renal Tolerance in ANCA-associated Vasculitis - RENATO Trial"; n 126; "Appearance of a success defined as (1) Delta sCreat > 30% (between D0 and week 26) AND (2) urine protein-to-creatinine (uPCR) < 1g/mmol"; 2028-11
NCT06246799
"Comparative Effectiveness of Two Initial Combination Therapies in Patients With Recent Onset Diabetes"; n 256; "number of subjects achieving HbA1c <6.5% at 6 months (Efficacy)"; 2029-06-30
NCT06336798
"Bioenergetic Effect of Pioglitazone in CLD-PH"; n 20; "Change in Mitochondrial metabolism parameters: Spare respiratory capacity"; 2028-02
NCT06399835
"Enavogliflozin vs. Pioglitazone on Glucose and Atherosclerosis"; n 120; "Changes of HbA1c from the baseline"; 2027-12-31
NCT06446531
"Prevention of Progression of Prediabetes, Obesity and CV Risk"; n 64; "Hemoglobin A1c Level (HBA1c)"; 2027-07
NCT06594172
"Early Application of Memantine and Pioglitazone to Protect Cognitive Function After Radiotherapy"; n 67; "the cumulative incidence of cognitive failure"; 2027-06-30
recorded 2026-09-01 · last checked 2026-09-04
Q10
Which running trial of Pioglitazone could settle insulin sensitivity?
NCT05919147 measures Change in skeletal muscle insulin sensitivity, reading out 2026-06-30.
2 open trials; n 24; "The Neuroendocrine Effects of Pioglitazone in Patients With Cancer and Cachexia"
Show the evidence
Trial
NCT05919147
"The Neuroendocrine Effects of Pioglitazone in Patients With Cancer and Cachexia"; n 24; "Change in skeletal muscle insulin sensitivity"; 2026-06-30
NCT06657209
"Normal-weight Diabetes: Adipocyte-directed Therapy With Pioglitazone or Tirzepatide"; n 104; "Insulin resistance in normal weight women with diabetes compared to those with no diabetes"; 2027-12-15
Q11
Which 147 trials of Pioglitazone posted no result?
Posted no result
147 of 147 completed trials
Registrations
NCT00521742, NCT00649012, NCT00649558, NCT00280865, NCT00449553 and NCT01161394, and 141 more
Completion dates
oldest 2003-01; newest 2024-07-23
Show the evidence
Trial
NCT00521742
2003-01
NCT00649012
2003-03
NCT00649558
2003-03
NCT00280865
2003-06
NCT00449553
2003-09
NCT01161394
2003-10
14 further recorded trials
NCT00013598
2004-03
NCT00331487
2004-03
NCT00598793
2004-03
NCT01799850
2004-03
NCT00672919
2004-08
NCT00676260
2004-08
NCT00377975
2004-11
NCT00174993
2005-01
NCT00982202
2005-01
NCT00494312
2005-06
NCT00097279
2005-08
NCT00242177
2005-10
NCT00762736
2005-10
NCT00143520
2005-12
Q12
At the median, Pioglitazone's trials enrolled 60.5 people — anything larger?
Median enrolment
60.5
Largest enrolment
1499650
Registered trials counted
400
Q13
What do 2688 spontaneous reports say about Pioglitazone — 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.
Pioglitazone appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 2688 reaction mentions were counted: bladder cancer 990; hypoglycaemia 279; oedema peripheral 239; cardiac failure congestive 231. open-targets-adr · CHEMBL1715 · 2026-06-24
Show the evidence
bladder cancer
990
hypoglycaemia
279
oedema peripheral
239
cardiac failure congestive
231
weight increased
226
haematuria
162
4 more recorded rows
cardiac failure
161
bladder transitional cell carcinoma
145
blood glucose increased
130
oedema
125
recorded 2026-06-24 · last checked 2026-09-04
Q14
Pioglitazone and CYP2C8, CYP3A4 and CYP1A1: shared by which compounds?
CYP2C8, CYP3A4 and CYP1A1 appear in Pioglitazone's recorded interaction sentences, 5 in all. openfda-label+europepmc · 2026-08-30
Interpretation pharmacokinetics
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CYP1A1pharmacokinetics
In vitro data demonstrate that multiple CYP isoforms are involved in the metabolism of pioglitazone, which include CYP2C8 and, to a lesser degree, CYP3A4 with additional contributions from a variety of other isoforms including the mainly extrahepatic CYP1A1.
CYP2C8
pharmacokinetics
In vitro data demonstrate that multiple CYP isoforms are involved in the metabolism of pioglitazone, which include CYP2C8 and, to a lesser degree, CYP3A4 with additional contributions from a variety of other isoforms including the mainly extrahepatic CYP1A1.
pharmacokinetics
In vivo study of pioglitazone in combination with gemfibrozil, a strong CYP2C8 inhibitor, showed that pioglitazone is a CYP2C8 substrate [ see Dosage and Administration ( 2.3 ) and Drug Interactions ( 7 ) ].
CYP3A4
pharmacokinetics
In vitro data demonstrate that multiple CYP isoforms are involved in the metabolism of pioglitazone, which include CYP2C8 and, to a lesser degree, CYP3A4 with additional contributions from a variety of other isoforms including the mainly extrahepatic CYP1A1.
pharmacokinetics
Urinary 6ß-hydroxycortisol/cortisol ratios measured in patients treated with pioglitazone hydrochloride showed that pioglitazone is not a strong CYP3A4 enzyme inducer.
recorded 2026-08-30 · last checked 2026-09-04
Q15
Was Pioglitazone studied with fasting?
fasting is named in Pioglitazone's label sentences: "Objective The study assessed the bioequivalence of a fixed-dose combination (FDC) of dapagliflozin 10 mg/pioglitazone 15 mg co-administered with the reference products Forxiga® 10 mg: AstraZeneca Pharmaceuticals LP, Indiana, USA and Pioglit® 15 mg: Sun Pharma Laboratories Ltd., Assam, India in…" openfda-label+europepmc · 2026-08-30
1 recorded statement; fasting
Show the evidence
fasting
Objective The study assessed the bioequivalence of a fixed-dose combination (FDC) of dapagliflozin 10 mg/pioglitazone 15 mg co-administered with the reference products Forxiga® 10 mg: AstraZeneca Pharmaceuticals LP, Indiana, USA and Pioglit® 15 mg: Sun Pharma Laboratories Ltd., Assam, India in healthy adult participants under fasting conditions.
recorded 2026-08-30 · last checked 2026-09-04
Q16
What is recorded about Pioglitazone and mTOR?
"Interventions included Ca<sup>2+</sup> chelation (BAPTA-AM), endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyrate, mammalian target of rapamycin (mTOR) inhibitor rapamycin, redox modulator Tempol, calcineurin inhibitor cyclosporine A, peroxisome-proliferator-activated receptor γ (PPARγ) agonist pioglitazone, and SERCA2 agonist…" — where Pioglitazone and mTOR appear together. Europe PMC · pathway abstract search · 2026-07-27
"Interventions included Ca<sup>2+</sup> chelation (BAPTA-AM), endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyrate, mammalian target of rapamycin (mTOR) inhibitor rapamycin, redox modulator Tempol, calcineurin inhibitor cyclosporine A, peroxisome-proliferator-activated receptor γ (PPARγ) agonist pioglitazone, and SERCA2 agonist [6]-gingerol."
AMPKPMID 41021735
"Pioglitazone activates AMP-activated protein kinase (AMPK), enhance autophagy, and modulate endoplasmic reticulum stress responses, suggesting a potential effect on ZAAT clearance."
autophagyPMID 41021735
"Pioglitazone activates AMP-activated protein kinase (AMPK), enhance autophagy, and modulate endoplasmic reticulum stress responses, suggesting a potential effect on ZAAT clearance."
AMPKPMID 41021735
"Huh7.5 cells expressing ZAAT (HuhZ) and Pi*Z transgenic mice were used to investigate pioglitazone treatment on hepatic ZAAT accumulation, autophagy activation, and AMPK signaling."
autophagyPMID 41021735
"Huh7.5 cells expressing ZAAT (HuhZ) and Pi*Z transgenic mice were used to investigate pioglitazone treatment on hepatic ZAAT accumulation, autophagy activation, and AMPK signaling."
AMPKPMID 41021735
"These findings demonstrate pioglitazone reduces hepatic ZAAT accumulation by activating AMPK and inducing autophagy in AATD-associated liver disease, supporting its potential for therapeutic repurposing."
4 more recorded rows
autophagyPMID 41021735
"These findings demonstrate pioglitazone reduces hepatic ZAAT accumulation by activating AMPK and inducing autophagy in AATD-associated liver disease, supporting its potential for therapeutic repurposing."
mTORPMID 41702311
"Metformin and pioglitazone have been found to promote metabolic (mTOR2) while inhibiting neoplastic (mTOR 1) pathways of the AMPK signaling network."
sirtuin
"Critically, pharmacological PPARγ activation by pioglitazone rescued NPAS2-driven metabolic dysfunction in vitro.Our study reveals NPAS2 as a critical node connecting circadian dysfunction to MASLD-HCC progression and identifies the NPAS2-SIRT1-PPARγ axis as a therapeutic target."
mTORPMID 41291936
"Inhibition of mTOR disrupted this axis and reversed the tolerogenic state, while pharmacological activation of PPARγ with pioglitazone mitigated asthma pathology in vivo."
recorded 2026-07-27 · last checked 2026-09-04
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