Drug · FAERS side-effect profile with label screen

Pioglitazone and Metformin side effects: what 1,267 FDA adverse event reports show

Pioglitazone And Metformin Hydrochloride · 30 reaction terms · 707 drug–reaction co-reports · data 2026-09-14

Drug class

Not stated in label

Label matched

Pioglitazone (Pioglitazone)

closest FDA label found for this product string; brand list suppressed because the label is a related product, not an exact match

Who reports

1,267 reports · 62% serious · 117 with death outcome · 47% female

openFDA FAERS counts, all years, deduplication not applied

Used for

Monotherapy and Combination Therapy Pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings [ see Clinical Studies ( 14 ) ]. Important Limitations of Use Pioglitazone tablets exert their antihyperglycemic effect only in the presence of endogenous insulin.

FDA label, Indications and Usage

What it is

Pioglitazone Tablets, USP are a thiazolidinedione and an agonist for peroxisome proliferator-activated receptor (PPAR) gamma that contains an oral antidiabetic medication: pioglitazone. Piogli.

FDA label, Description section

Boxed warning

CONGESTIVE HEART FAILURE Thiazolidinediones, including pioglitazone hydrochloride, cause or exacerbate congestive heart failure in some patients [ see Warnings and Precautions ( 5.1 ) ]. After initiation of pioglitaz.

FDA label

How to read this page. FAERS is a spontaneous-reporting system: counts are not incidence rates and a signal is not proof of causation. Each reaction below is run through an automated screen — is the term in the FDA label (known), in the indications (the disease being treated), an administrative/coding term, or none of these (unlabeled)? That screen is mechanical text matching, not a causality assessment. The 30 hand-written Bradford Hill assessments are on the causality assessment page. Not medical advice.

Causality screen of the 23 strongest signals

Labeled — boxed warning 2Labeled adverse reaction 1Labeled (related wording) 2Reporting / coding artifact 3Lab value / disease marker 2Not in label — unassessed 13

What the badges mean

Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.

Strongest disproportionality signals

Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 7 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.

Show: hide coding/lab/outcome terms hide indication terms unlabeled only hide PRR-only

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Bladder cancer	299	83.5 75.6–92.2ROR 108.9 · χ² 24,226 / p <1e-300	82.6 EB05 75.1 · IC025 +6.0 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 76.0 · ♀ 23% (drug 47%)	no trial data cached
Blood glucose decreased	45	15.5 11.6–20.6ROR 16.0 · χ² 595 / p 9e-132	15.3 EB05 11.8 · IC025 +3.2 3/3 methods agree	Labeled — boxed warning synonym match	serious PRR 9.8 · 85% consumer	no trial data cached
End stage renal disease	12	10.8 6.1–18.9ROR 10.9 · χ² 97 / p 3e-23	9.0 EB05 5.0 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 10.0	no trial data cached
Injection site nodule	7	10.6 5.0–22.1ROR 10.6 · χ² 51 / p 4e-13	7.6 EB05 3.6 · IC025 +1.4 3/3 methods agree	Not in label — unassessed	serious n=1	no trial data cached
Blood glucose fluctuation	7	10.5 5.0–22.1ROR 10.6 · χ² 51 / p 4e-13	7.6 EB05 3.6 · IC025 +1.4 3/3 methods agree	Lab value / disease marker	serious n=2	no trial data cached
Anorexia	8	10.1 5.1–20.2ROR 10.2 · χ² 57 / p 2e-14	7.6 EB05 3.8 · IC025 +1.5 3/3 methods agree	Labeled adverse reaction exact term	–	no trial data cached
Blood glucose increased	109	9.5 8.0–11.4ROR 10.3 · χ² 832 / p 3e-183	9.4 EB05 7.9 · IC025 +2.9 3/3 methods agree	Labeled (related wording) related wording	serious PRR 6.4 · 84% consumer	no trial data cached
Flushing	52	8.4 6.5–11.0ROR 8.7 · χ² 335 / p 5e-75	8.0 EB05 6.3 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 1.2 · 90% consumer	no trial data cached
Diabetes mellitus inadequate control	9	8.4 4.4–16.1ROR 8.5 · χ² 52 / p 3e-13	6.4 EB05 3.5 · IC025 +1.5 3/3 methods agree	Labeled (related wording) related wording	serious PRR 9.2	no trial data cached
Coronary artery occlusion	6	7.2 3.2–16.0ROR 7.2 · χ² 26 / p 2e-7	5.0 EB05 2.4 · IC025 +0.9 3/3 methods agree	Not in label — unassessed	serious PRR 6.7	no trial data cached
Eructation (belching)	8	7.0 3.5–13.9ROR 7.0 · χ² 35 / p 2e-9	5.2 EB05 2.8 · IC025 +1.2 3/3 methods agree	Not in label — unassessed	serious n=1	no trial data cached
Metastases to liver	7	6.6 3.2–13.8ROR 6.6 · χ² 28 / p 6e-8	4.8 EB05 2.5 · IC025 +1.0 3/3 methods agree	Not in label — unassessed	serious PRR 6.2	no trial data cached
Erectile dysfunction	10	6.4 3.5–11.9ROR 6.5 · χ² 41 / p 9e-11	5.1 EB05 3.0 · IC025 +1.3 3/3 methods agree	Not in label — unassessed	serious PRR 6.9	no trial data cached
Hunger	5	6.2 2.6–14.8ROR 6.2 · χ² 17 / p 2e-5	4.2 EB05 2.0 · IC025 +0.5	Not in label — unassessed	–	no trial data cached
Glycosylated haemoglobin increased	9	5.9 3.1–11.3ROR 5.9 · χ² 32 / p 8e-9	4.7 EB05 2.6 · IC025 +1.1 3/3 methods agree	Lab value / disease marker	serious PRR 2.8	no trial data cached
Metastases to bone	5	5.1 2.1–12.1ROR 5.1 · χ² 12 / p 2e-4	3.7 EB05 1.7 · IC025 +0.3	Not in label — unassessed	serious PRR 4.7	no trial data cached
Pharmaceutical product complaint	8	5.0 2.5–10.0ROR 5.1 · χ² 22 / p 1e-6	4.0 EB05 2.2 · IC025 +0.8 3/3 methods agree	Not in label — unassessed	serious PRR 0.9	no trial data cached
Injection site haemorrhage	21	4.4 2.9–6.7ROR 4.4 · χ² 52 / p 3e-13	4.0 EB05 2.8 · IC025 +1.3 3/3 methods agree	Not in label — unassessed	serious PRR 1.4 · 95% consumer	no trial data cached
Drug prescribing error	5	4.2 1.8–10.2ROR 4.3 · χ² 9 / p 0.001	3.2 EB05 1.6 · IC025 +0.2	Reporting / coding artifact	serious n=2	no trial data cached
Injection site bruising	20	4.2 2.7–6.5ROR 4.2 · χ² 46 / p 7e-12	3.9 EB05 2.7 · IC025 +1.2 3/3 methods agree	Not in label — unassessed	serious PRR 2.4 · ♀ 75% (drug 47%)	no trial data cached
Drug effect decreased	11	3.3 1.8–6.0ROR 3.4 · χ² 16 / p 4e-5	3.0 EB05 1.8 · IC025 +0.6	Reporting / coding artifact	–	no trial data cached
Wrong technique in drug usage process	6	2.7 1.2–6.0ROR 2.7 · χ² 5 / p 0.014	2.4 EB05 1.2 · IC025 -0.2 PRR-only: not supported by EBGM or IC	Reporting / coding artifact	serious PRR 4.1	no trial data cached
Renal cancer	7	2.4 1.1–5.0ROR 2.4 · χ² 4 / p 0.018	2.2 EB05 1.2 · IC025 -0.2 PRR-only: not supported by EBGM or IC	Not in label — unassessed	serious PRR 2.2	no trial data cached

Trial evidence (ClinicalTrials.gov)

Trial cross-check not yet run for this drug (ClinicalTrials.gov pull covers the 800 most-reported drugs first).

Most frequently reported reactions

By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Bladder cancer	299	83.5 75.6–92.2ROR 108.9 · χ² 24,226 / p <1e-300	82.6 EB05 75.1 · IC025 +6.0 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 76.0 · ♀ 23% (drug 47%)	no trial data cached
Blood glucose increased	109	9.5 8.0–11.4ROR 10.3 · χ² 832 / p 3e-183	9.4 EB05 7.9 · IC025 +2.9 3/3 methods agree	Labeled (related wording) related wording	serious PRR 6.4 · 84% consumer	no trial data cached
Flushing	52	8.4 6.5–11.0ROR 8.7 · χ² 335 / p 5e-75	8.0 EB05 6.3 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 1.2 · 90% consumer	no trial data cached
Blood glucose decreased	45	15.5 11.6–20.6ROR 16.0 · χ² 595 / p 9e-132	15.3 EB05 11.8 · IC025 +3.2 3/3 methods agree	Labeled — boxed warning synonym match	serious PRR 9.8 · 85% consumer	no trial data cached
Injection site haemorrhage	21	4.4 2.9–6.7ROR 4.4 · χ² 52 / p 3e-13	4.0 EB05 2.8 · IC025 +1.3 3/3 methods agree	Not in label — unassessed	serious PRR 1.4 · 95% consumer	no trial data cached
Injection site bruising	20	4.2 2.7–6.5ROR 4.2 · χ² 46 / p 7e-12	3.9 EB05 2.7 · IC025 +1.2 3/3 methods agree	Not in label — unassessed	serious PRR 2.4 · ♀ 75% (drug 47%)	no trial data cached
End stage renal disease	12	10.8 6.1–18.9ROR 10.9 · χ² 97 / p 3e-23	9.0 EB05 5.0 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 10.0	no trial data cached
Drug effect decreased	11	3.3 1.8–6.0ROR 3.4 · χ² 16 / p 4e-5	3.0 EB05 1.8 · IC025 +0.6	Reporting / coding artifact	–	no trial data cached
Erectile dysfunction	10	6.4 3.5–11.9ROR 6.5 · χ² 41 / p 9e-11	5.1 EB05 3.0 · IC025 +1.3 3/3 methods agree	Not in label — unassessed	serious PRR 6.9	no trial data cached
Glycosylated haemoglobin increased	9	5.9 3.1–11.3ROR 5.9 · χ² 32 / p 8e-9	4.7 EB05 2.6 · IC025 +1.1 3/3 methods agree	Lab value / disease marker	serious PRR 2.8	no trial data cached
Diabetes mellitus inadequate control	9	8.4 4.4–16.1ROR 8.5 · χ² 52 / p 3e-13	6.4 EB05 3.5 · IC025 +1.5 3/3 methods agree	Labeled (related wording) related wording	serious PRR 9.2	no trial data cached
Prostate cancer	8	1.6 0.8–3.3ROR 1.6 · χ² 1 / p 0.120	1.6 EB05 0.9 · IC025 -0.6 PRR-only: not supported by EBGM or IC	Not in label — unassessed	serious PRR 1.5	no trial data cached
Pharmaceutical product complaint	8	5.0 2.5–10.0ROR 5.1 · χ² 22 / p 1e-6	4.0 EB05 2.2 · IC025 +0.8 3/3 methods agree	Not in label — unassessed	serious PRR 0.9	no trial data cached
Eructation (belching)	8	7.0 3.5–13.9ROR 7.0 · χ² 35 / p 2e-9	5.2 EB05 2.8 · IC025 +1.2 3/3 methods agree	Not in label — unassessed	serious n=1	no trial data cached
Anorexia	8	10.1 5.1–20.2ROR 10.2 · χ² 57 / p 2e-14	7.6 EB05 3.8 · IC025 +1.5 3/3 methods agree	Labeled adverse reaction exact term	–	no trial data cached

Unlabeled candidate signals

These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.

Flushing — n=52, PRR 8.4
Injection site haemorrhage — n=21, PRR 4.4
Injection site bruising — n=20, PRR 4.2

✓ A hand-written Bradford Hill causality assessment exists for this drug: Pioglitazone ↔ Bladder cancer.

Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.

Common questions

What are the most reported side effects of Pioglitazone and Metformin?

In FDA FAERS, the most frequently co-reported reaction terms for Pioglitazone and Metformin are bladder cancer, blood glucose increased, flushing, blood glucose decreased, injection site haemorrhage, injection site bruising. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.

Does Pioglitazone and Metformin have an FDA boxed warning?

Yes. The current FDA label carries a boxed warning: CONGESTIVE HEART FAILURE Thiazolidinediones, including pioglitazone hydrochloride, cause or exacerbate congestive heart failure in some patients [ see Warnings and Precautions ( 5.1 ) ]. After initiation of pioglitaz.

Do FAERS signals prove that Pioglitazone and Metformin causes these side effects?

No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.

Sources & methods

FDA label via openFDA (set ID 22569835-bc9f-7787-e063-6394a90a6232, effective 20260119; matched on openfda.generic_name.exact:"PIOGLITAZONE")
Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA count= aggregation, field patient.drug.openfda.generic_name.exact, 30 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction
Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
Seriousness and sex counts from openFDA count=serious, patient.patientsex, seriousnessdeath

Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.