Trial Outcomes & Findings for Pioglitazone Special Drug Use Surveillance "Metabolic Syndrome in Patients With Type 2 Diabetes Mellitus" (NCT NCT02002975)

NCT ID: NCT02002975

Last Updated: 2019-01-24

Results Overview

Cerebral and cardiovascular events (Macroangiopathy) include the following: Sudden death, Cerebral infarction, Cerebral hemorrhage, Subarachnoid hemorrhage, Acute myocardial infarction, Angina pectoris requiring intervention or hospitalization for treatment, Cardiac failure requiring hospitalization for treatment, Atrial fibrillation, Aortic dissection. Reported data was frequency of participants who met at least one new cerebral and cardiovascular event throughout this study.

• Recruitment status: COMPLETED
• Target enrollment: 18223 participants
• Primary outcome timeframe: From Baseline, Up to 3 Years
• Results posted on: 2019-01-24

Participant Flow

Participants took part in the study at 1203 investigative sites in Japan, from 16 October 2007 to 30 June 2013.

Participants with a historical diagnosis of type 2 diabetes mellitus were enrolled to receive pioglitazone 15 milligram (mg) - 30 mg tablet, orally, once daily for up to 3 years.

Participant milestones

Measure	Pioglitazone Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Overall Study STARTED	18223
Overall Study COMPLETED	17651
Overall Study NOT COMPLETED	572

Reasons for withdrawal

Measure	Pioglitazone Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Overall Study Case Report Forms Uncollected	135
Overall Study Protocol Deviation	437

Baseline Characteristics

Pioglitazone Special Drug Use Surveillance "Metabolic Syndrome in Patients With Type 2 Diabetes Mellitus"

Baseline characteristics by cohort

Measure	Pioglitazone n=17651 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Age, Continuous	59.9 Years STANDARD_DEVIATION 10.0 • n=93 Participants
Sex: Female, Male Female	7037 Participants n=93 Participants
Sex: Female, Male Male	10614 Participants n=93 Participants
Region of Enrollment Japan	17651 Participants n=93 Participants
Duration of Type 2 Diabetes Mellitus < 1 year	3076 Participants 17.4 • n=93 Participants
Duration of Type 2 Diabetes Mellitus 1 - < 5 years	5620 Participants 31.8 • n=93 Participants
Duration of Type 2 Diabetes Mellitus 5 - < 10 years	3685 Participants 20.9 • n=93 Participants
Duration of Type 2 Diabetes Mellitus ≥ 10 years	2783 Participants 15.8 • n=93 Participants
Duration of Type 2 Diabetes Mellitus Unknown	2487 Participants 14.1 • n=93 Participants
BMI	25.78 Kilogram (kg)/m^2 STANDARD_DEVIATION 4.17 • n=93 Participants
Waist Circumference	89.31 Centimeter (cm) STANDARD_DEVIATION 10.22 • n=93 Participants
Fasting Blood Glucose	151.5 Milligram (mg)/dL STANDARD_DEVIATION 47.9 • n=93 Participants
Haemoglobin A1c (HbA1c) [National Glycohemoglobin Standardization Program (NGSP)]	8.12 Percent STANDARD_DEVIATION 1.58 • n=93 Participants
Clinical Systolic Blood Pressure (SBP)	134.4 mmHg STANDARD_DEVIATION 16.0 • n=93 Participants
Clinical Diastolic Blood Pressure (DBP)	78.5 mmHg STANDARD_DEVIATION 10.7 • n=93 Participants
Total Cholesterol	208.0 mg/dL STANDARD_DEVIATION 40.6 • n=93 Participants
HDL Cholesterol	54.0 mg/dL STANDARD_DEVIATION 15.2 • n=93 Participants
Fasting Triglyceride	157.4 mg/dL STANDARD_DEVIATION 104.1 • n=93 Participants
Number of Participants Who Was Current Smoker	4041 Participants n=93 Participants
Number of Participants Who Was Current Drinker	7112 Participants n=93 Participants
Number of Participants Who Had Medical History or Medical Complications	15051 Participants n=93 Participants

PRIMARY outcome

Timeframe: From Baseline, Up to 3 Years

Population: Full Analysis Set included all participants who had efficacy data at baseline and post-baseline (3 Month) available.

Cerebral and cardiovascular events (Macroangiopathy) include the following: Sudden death, Cerebral infarction, Cerebral hemorrhage, Subarachnoid hemorrhage, Acute myocardial infarction, Angina pectoris requiring intervention or hospitalization for treatment, Cardiac failure requiring hospitalization for treatment, Atrial fibrillation, Aortic dissection. Reported data was frequency of participants who met at least one new cerebral and cardiovascular event throughout this study.

Outcome measures

Measure	Pioglitazone n=17651 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Percentage of Participants Who Met at Least One New Cerebral and Cardiovascular Events	1.01 Percentage of Participants

PRIMARY outcome

Timeframe: From Baseline and final assessment point (Up to 3 Years)

Population: Full Analysis Set included all participants who had efficacy data at baseline and post-baseline (3 Month) available.

Changes from baseline in metabolic syndrome parameters at final assessment point (up to 3 years) were reported. The reported data on this outcome measure is in body weight as a one of metabolic syndrome parameters and for each gender (male/female).

Outcome measures

Measure	Pioglitazone n=13653 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Changes From Baseline in Metabolic Syndrome Parameters (Body Weight) at Final Assessment Point Male Participants	1.27 kg Standard Deviation 4.76
Changes From Baseline in Metabolic Syndrome Parameters (Body Weight) at Final Assessment Point Female Participants	1.53 kg Standard Deviation 4.61

PRIMARY outcome

Timeframe: From Baseline and final assessment point (Up to 3 Years)

Population: Full Analysis Set included all participants who had efficacy data at baseline and post-baseline (3 Month) available.

Changes from baseline in metabolic syndrome parameters at final assessment point (up to 3 years) were reported. The reported data on this outcome measure is in waist circumference as a one of metabolic syndrome parameters and for each gender (male/female).

Outcome measures

Measure	Pioglitazone n=11418 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Changes From Baseline in Metabolic Syndrome Parameters (Waist Circumference) at Final Assessment Point Male Participants	0.51 cm Standard Deviation 5.18
Changes From Baseline in Metabolic Syndrome Parameters (Waist Circumference) at Final Assessment Point Female Participants	0.54 cm Standard Deviation 6.06

PRIMARY outcome

Timeframe: From Baseline and final assessment point (Up to 3 Years)

Population: Full Analysis Set included all participants who had efficacy data at baseline and post-baseline (3 Month) available. Here number of participants analyzed are participants evaluable for this outcome measure.

Changes from baseline in metabolic syndrome parameters at final assessment point (up to 3 years) were reported. The reported data on this outcome measure is in HbA1c (NGSP) as a one of metabolic syndrome parameters.

Outcome measures

Measure	Pioglitazone n=16558 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Changes From Baseline in Metabolic Syndrome Parameters (Haemoglobin A1c (HbA1c) [National Glycohemoglobin Standardization Program (NGSP)]) at Final Assessment Point	-1.04 Percent Standard Deviation 1.46

PRIMARY outcome

Timeframe: From Baseline and final assessment point (Up to 3 Years)

Population: Full Analysis Set included all participants who had efficacy data at baseline and post-baseline (3 Month) available. Here number of participants analyzed are participants evaluable for this outcome measure.

Changes from baseline in metabolic syndrome parameters at final assessment point (up to 3 years) were reported. The reported data on this outcome measure is in fasting blood glucose as a one of metabolic syndrome parameters.

Outcome measures

Measure	Pioglitazone n=8464 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Changes From Baseline in Metabolic Syndrome Parameters (Fasting Blood Glucose) at Final Assessment Point	-25.4 mg/dL Standard Deviation 48.3

PRIMARY outcome

Timeframe: From Baseline and final assessment point (Up to 3 Years)

Population: Full Analysis Set included all participants who had efficacy data at baseline and post-baseline (3 Month) available. Here number of participants analyzed are participants evaluable for this outcome measure.

Changes from baseline in metabolic syndrome parameters at final assessment point (up to 3 years) were reported. The reported data on this outcome measure is in fasting blood insulin level as a one of metabolic syndrome parameters.

Outcome measures

Measure	Pioglitazone n=1379 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Changes From Baseline in Metabolic Syndrome Parameters (Fasting Blood Insulin Level) at Final Assessment Point	-1.58 micro unit/mL Standard Deviation 8.38

PRIMARY outcome

Timeframe: From Baseline and final assessment point (Up to 3 Years)

Population: Full Analysis Set included all participants who had efficacy data at baseline and post-baseline (3 Month) available. Here number of participants analyzed are participants evaluable for this outcome measure.

Changes from baseline in metabolic syndrome parameters at final assessment point (up to 3 years) were reported. The reported data on this outcome measure is in total cholesterol level as a one of metabolic syndrome parameters.

Outcome measures

Measure	Pioglitazone n=10034 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Changes From Baseline in Metabolic Syndrome Parameters (Total Cholesterol Level) at Final Assessment Point	-9.0 mg/dL Standard Deviation 39.3

PRIMARY outcome

Timeframe: From Baseline and final assessment point (Up to 3 Years)

Population: Full Analysis Set included all participants who had efficacy data at baseline and post-baseline (3 Month) available. Here number of participants analyzed are participants evaluable for this outcome measure.

Changes from baseline in metabolic syndrome parameters at final assessment point (up to 3 years) were reported. The reported data on this outcome measure is in HDL cholesterol level as a one of metabolic syndrome parameters.

Outcome measures

Measure	Pioglitazone n=15679 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Changes From Baseline in Metabolic Syndrome Parameters (High-density Lipoprotein (HDL) Cholesterol Level) at Final Assessment Point	3.1 mg/dL Standard Deviation 12.0

PRIMARY outcome

Timeframe: From Baseline and final assessment point (Up to 3 Years)

Population: Full Analysis Set included all participants who had efficacy data at baseline and post-baseline (3 Month) available. Here number of participants analyzed are participants evaluable for this outcome measure.

Changes from baseline in metabolic syndrome parameters at final assessment point (up to 3 years) were reported. The reported data on this outcome measure is in fasting triglyceride level as a one of metabolic syndrome parameters.

Outcome measures

Measure	Pioglitazone n=10808 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Changes From Baseline in Metabolic Syndrome Parameters (Fasting Triglyceride Level) at Final Assessment Point	-28.7 mg/dL Standard Deviation 88.8

PRIMARY outcome

Timeframe: From Baseline and final assessment point (Up to 3 Years)

Population: Full Analysis Set included all participants who had efficacy data at baseline and post-baseline (3 Month) available. Here number of participants analyzed are participants evaluable for this outcome measure.

Changes from baseline in metabolic syndrome parameters at final assessment point (up to 3 years) were reported. The reported data on this outcome measure is in systolic blood pressure as a one of metabolic syndrome parameters.

Outcome measures

Measure	Pioglitazone n=16583 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Changes From Baseline in Metabolic Syndrome Parameters (Systolic Blood Pressure) at Final Assessment Point	-3.1 mmHg Standard Deviation 16.2

PRIMARY outcome

Timeframe: From Baseline and final assessment point (Up to 3 Years)

Population: Full Analysis Set included all participants who had efficacy data at baseline and post-baseline (3 Month) available. Here number of participants analyzed are participants evaluable for this outcome measure.

Changes from baseline in metabolic syndrome parameters at final assessment point (up to 3 years) were reported. The reported data on this outcome measure is in diastolic blood pressure as a one of metabolic syndrome parameters.

Outcome measures

Measure	Pioglitazone n=16583 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Changes From Baseline in Metabolic Syndrome Parameters (Diastolic Blood Pressure) at Final Assessment Point	-2.8 mmHg Standard Deviation 10.8

SECONDARY outcome

Timeframe: From Baseline and final assessment point (Up to 3 Years)

Population: Full Analysis Set included all participants who had efficacy data at baseline and post-baseline (3 Month) available.

Changes from baseline in HbA1c (NGSP) with number of MetS-related factor were reported instead. Risk factors included Glucose Intolerance, Complication of Hypertension, Complication of Hyperlipidemia, Obesity, and Family History of Diabetes in Second-Degree Relatives.

Outcome measures

Measure	Pioglitazone n=17651 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Changes From Baseline in HbA1c (NGSP) With Number of Metabolic Syndrome-related Risk Factor (MetS-related Factor) at Final Assessment Point One Factor	-0.89 Percent Standard Deviation 1.68
Changes From Baseline in HbA1c (NGSP) With Number of Metabolic Syndrome-related Risk Factor (MetS-related Factor) at Final Assessment Point Two Factor	-1.00 Percent Standard Deviation 1.53
Changes From Baseline in HbA1c (NGSP) With Number of Metabolic Syndrome-related Risk Factor (MetS-related Factor) at Final Assessment Point Three Factor	-1.04 Percent Standard Deviation 1.42
Changes From Baseline in HbA1c (NGSP) With Number of Metabolic Syndrome-related Risk Factor (MetS-related Factor) at Final Assessment Point Four Factor	-1.04 Percent Standard Deviation 1.39

SECONDARY outcome

Timeframe: 3 Years

Population: Outcome measure, "Association between patient baseline characteristics, including any metabolic syndrome-related risk factors, and onset of new cerebral and cardiovascular events", on protocol section could not be summarized because study protocol was not defined what is the specific data for association precisely and there were no data to report.

Outcome measures

Outcome data not reported

Adverse Events

Pioglitazone

Serious events: 82 serious events

Other events: 467 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pioglitazone n=17651 participants at risk Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Infections and infestations Bronchitis	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Infections and infestations Cellulitis	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Infections and infestations Diabetic gangrene	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.01% 2/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Metabolism and nutrition disorders Hyperammonaemia	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Metabolism and nutrition disorders Hypoglycaemia	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Nervous system disorders Cerebral haemorrhage	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Nervous system disorders Cerebral infarction	0.05% 9/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Nervous system disorders Spinocerebellar disorder	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Eye disorders Diabetic retinopathy	0.01% 2/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Cardiac disorders Acute myocardial infarction	0.06% 11/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Cardiac disorders Angina pectoris	0.03% 5/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Cardiac disorders Atrial fibrillation	0.02% 3/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Cardiac disorders Cardiac failure	0.10% 17/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Cardiac disorders Cardiac failure congestive	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Hepatobiliary disorders Bile duct stone	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Hepatobiliary disorders Cholelithiasis	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Hepatobiliary disorders Hepatic failure	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Hepatobiliary disorders Drug-induced liver injury	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Renal and urinary disorders Proteinuria	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Renal and urinary disorders Diabetic nephropathy	0.02% 3/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
General disorders Death	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
General disorders Oedema peripheral	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
General disorders Sudden death	0.04% 7/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Investigations Alanine aminotransferase increased	0.01% 2/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Investigations Aspartate aminotransferase increased	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Investigations Blood calcium increased	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Investigations Blood creatine phosphokinase increased	0.01% 2/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Investigations Blood creatinine increased	0.01% 2/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Investigations Blood potassium increased	0.01% 2/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Investigations Gamma-glutamyltransferase increased	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Investigations Haemoglobin decreased	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Investigations Protein urine present	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Investigations Brain natriuretic peptide increased	0.01% 2/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Investigations Brain natriuretic peptide abnormal	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Injury, poisoning and procedural complications Femur fracture	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Injury, poisoning and procedural complications Spinal compression fracture	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Surgical and medical procedures Peripheral revascularisation	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.01% 1/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.

Other adverse events

Measure	Pioglitazone n=17651 participants at risk Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 3 years before or after breakfast in participants based upon the disease severity. Participants received interventions as part of routine medical care.
General disorders Oedema	1.6% 279/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.
General disorders Oedema peripheral	1.1% 188/17651 • Up to 3 Years Only adverse drug reactions (ADRs) were collected in this study. ADRs are adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms/diseases temporally associated with the use of a medicinal product reported throughout the study.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER