Type 2 Diabetes Mellitus
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this survey is to determine the onset of new cerebral and cardiovascular events and changes in metabolic syndrome parameters in patients with type 2 diabetes mellitus on long-term pioglitazone (Actos Tablets) treatment.
Detailed description
This is a special drug use surveillance on long-term use of pioglitazone (Actos Tablets) in patients with type 2 diabetes mellitus, designed to determine the onset of new cerebral and cardiovascular events and changes in metabolic syndrome parameters, and to analyze the association between patient baseline characteristics, including any metabolic syndrome-related risk factors, and the onset of new cerebral and cardiovascular events in an exploratory setting. Participants will be patients with type 2 diabetes mellitus. The planned sample size is 20000. The usual adult dosage is 15 to 30 mg of pioglitazone administered orally once daily before or after breakfast.
Interventions
DRUGPioglitazone
Pioglitazone tablets
Sponsors
Takeda
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have type 2 diabetes mellitus and have undergone measurements for all of the following parameters to be included in this survey: Waist circumference, height, body weight, blood pressure, Haemoglobin A1c (HbA1c), fasting triglyceride, High-density Lipoprotein (HDL)-cholesterol
Exclusion criteria
* Patients meeting any of the following criteria (1) to (5) will be excluded: 1. Patients with any contraindications to pioglitazone (Actos Tablets) treatment as specified below: Cardiac failure, history of cardiac failure, severe ketosis, diabetic coma or precoma, type 1 diabetes mellitus, serious hepatic dysfunction, serious renal dysfunction, severe infection, perioperative state, serious trauma, history of hypersensitivity to any ingredients of pioglitazone (Actos Tablets), pregnancy or possible pregnancy 2. Patients aged \< 20 or ≥ 75 years 3. Patients who currently have or have had any of the following: myocardial infarction, angina pectoris, cardiomyopathy, hypertensive heart disease (including left ventricular hypertrophy with cardiac hypofunction\*), atrial fibrillation, atrial flutter, valvular disease, aortic dissection, cerebral infarction, cerebral hemorrhage (including subarachnoid hemorrhage). (\*Reduced cardiac function is roughly defined as having a brain natriuretic peptide \[BNP\] ≥ 40 pg/mL.) 4. Patients who have taken pioglitazone (Actos Tablets) within 3 months before enrollment in this survey 5. Patients who have been enrolled in the candesartan cilexetil (Blopress) special drug use surveillance hypertension: survey on metabolic equivalents (MetS) (Challenge-MetS) at each medical institution.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline in Metabolic Syndrome Parameters (Diastolic Blood Pressure) at Final Assessment Point | From Baseline and final assessment point (Up to 3 Years) | 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. |
| Changes From Baseline in Metabolic Syndrome Parameters (Fasting Triglyceride Level) at Final Assessment Point | From Baseline and final assessment point (Up to 3 Years) | 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. |
| Changes From Baseline in Metabolic Syndrome Parameters (Systolic Blood Pressure) at Final Assessment Point | From Baseline and final assessment point (Up to 3 Years) | 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. |
| Percentage of Participants Who Met at Least One New Cerebral and Cardiovascular Events | From Baseline, Up to 3 Years | 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. |
| Changes From Baseline in Metabolic Syndrome Parameters (Body Weight) at Final Assessment Point | From Baseline and final assessment point (Up to 3 Years) | 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). |
| Changes From Baseline in Metabolic Syndrome Parameters (Waist Circumference) at Final Assessment Point | From Baseline and final assessment point (Up to 3 Years) | 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). |
| Changes From Baseline in Metabolic Syndrome Parameters (Haemoglobin A1c (HbA1c) [National Glycohemoglobin Standardization Program (NGSP)]) at Final Assessment Point | From Baseline and final assessment point (Up to 3 Years) | 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. |
| Changes From Baseline in Metabolic Syndrome Parameters (Fasting Blood Glucose) at Final Assessment Point | From Baseline and final assessment point (Up to 3 Years) | 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. |
| Changes From Baseline in Metabolic Syndrome Parameters (Fasting Blood Insulin Level) at Final Assessment Point | From Baseline and final assessment point (Up to 3 Years) | 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. |
| Changes From Baseline in Metabolic Syndrome Parameters (Total Cholesterol Level) at Final Assessment Point | From Baseline and final assessment point (Up to 3 Years) | 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. |
| Changes From Baseline in Metabolic Syndrome Parameters (High-density Lipoprotein (HDL) Cholesterol Level) at Final Assessment Point | From Baseline and final assessment point (Up to 3 Years) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Association Between Patient Baseline Characteristics, Including Any Metabolic Syndrome-related Risk Factors, and Onset of New Cerebral and Cardiovascular Events | 3 Years | — |
| Changes From Baseline in HbA1c (NGSP) With Number of Metabolic Syndrome-related Risk Factor (MetS-related Factor) at Final Assessment Point | From Baseline and final assessment point (Up to 3 Years) | 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. |
Participant flow
Recruitment details
Participants took part in the study at 1203 investigative sites in Japan, from 16 October 2007 to 30 June 2013.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 17,651 |
| Total | 17,651 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Case Report Forms Uncollected | 135 |
| Overall Study | Protocol Deviation | 437 |
Baseline characteristics
| Characteristic | Pioglitazone |
|---|---|
| Age, Continuous | 59.9 Years STANDARD_DEVIATION 10 |
| BMI | 25.78 Kilogram (kg)/m^2 STANDARD_DEVIATION 4.17 |
| Clinical Diastolic Blood Pressure (DBP) | 78.5 mmHg STANDARD_DEVIATION 10.7 |
| Clinical Systolic Blood Pressure (SBP) | 134.4 mmHg STANDARD_DEVIATION 16 |
| Duration of Type 2 Diabetes Mellitus ≥ 10 years | 2783 Participants 15.8 |
| Duration of Type 2 Diabetes Mellitus 1 - < 5 years | 5620 Participants 31.8 |
| Duration of Type 2 Diabetes Mellitus < 1 year | 3076 Participants 17.4 |
| Duration of Type 2 Diabetes Mellitus 5 - < 10 years | 3685 Participants 20.9 |
| Duration of Type 2 Diabetes Mellitus Unknown | 2487 Participants 14.1 |
| Fasting Blood Glucose | 151.5 Milligram (mg)/dL STANDARD_DEVIATION 47.9 |
| Fasting Triglyceride | 157.4 mg/dL STANDARD_DEVIATION 104.1 |
| Haemoglobin A1c (HbA1c) [National Glycohemoglobin Standardization Program (NGSP)] | 8.12 Percent STANDARD_DEVIATION 1.58 |
| HDL Cholesterol | 54.0 mg/dL STANDARD_DEVIATION 15.2 |
| Number of Participants Who Had Medical History or Medical Complications | 15051 Participants |
| Number of Participants Who Was Current Drinker | 7112 Participants |
| Number of Participants Who Was Current Smoker | 4041 Participants |
| Region of Enrollment Japan | 17651 Participants |
| Sex: Female, Male Female | 7037 Participants |
| Sex: Female, Male Male | 10614 Participants |
| Total Cholesterol | 208.0 mg/dL STANDARD_DEVIATION 40.6 |
| Waist Circumference | 89.31 Centimeter (cm) STANDARD_DEVIATION 10.22 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 467 / 17,651 |
| serious Total, serious adverse events | 82 / 17,651 |
Outcome results
Primary
Changes From Baseline in Metabolic Syndrome Parameters (Body Weight) at Final Assessment Point
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Changes From Baseline in Metabolic Syndrome Parameters (Body Weight) at Final Assessment Point | Male Participants | 1.27 kg | Standard Deviation 4.76 |
| Pioglitazone | Changes From Baseline in Metabolic Syndrome Parameters (Body Weight) at Final Assessment Point | Female Participants | 1.53 kg | Standard Deviation 4.61 |
Primary
Changes From Baseline in Metabolic Syndrome Parameters (Diastolic Blood Pressure) at Final Assessment Point
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | Changes From Baseline in Metabolic Syndrome Parameters (Diastolic Blood Pressure) at Final Assessment Point | -2.8 mmHg | Standard Deviation 10.8 |
Primary
Changes From Baseline in Metabolic Syndrome Parameters (Fasting Blood Glucose) at Final Assessment Point
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | Changes From Baseline in Metabolic Syndrome Parameters (Fasting Blood Glucose) at Final Assessment Point | -25.4 mg/dL | Standard Deviation 48.3 |
Primary
Changes From Baseline in Metabolic Syndrome Parameters (Fasting Blood Insulin Level) at Final Assessment Point
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | 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
Changes From Baseline in Metabolic Syndrome Parameters (Fasting Triglyceride Level) at Final Assessment Point
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | Changes From Baseline in Metabolic Syndrome Parameters (Fasting Triglyceride Level) at Final Assessment Point | -28.7 mg/dL | Standard Deviation 88.8 |
Primary
Changes From Baseline in Metabolic Syndrome Parameters (Haemoglobin A1c (HbA1c) [National Glycohemoglobin Standardization Program (NGSP)]) at Final Assessment Point
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | 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
Changes From Baseline in Metabolic Syndrome Parameters (High-density Lipoprotein (HDL) Cholesterol Level) at Final Assessment Point
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | Changes From Baseline in Metabolic Syndrome Parameters (High-density Lipoprotein (HDL) Cholesterol Level) at Final Assessment Point | 3.1 mg/dL | Standard Deviation 12 |
Primary
Changes From Baseline in Metabolic Syndrome Parameters (Systolic Blood Pressure) at Final Assessment Point
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | Changes From Baseline in Metabolic Syndrome Parameters (Systolic Blood Pressure) at Final Assessment Point | -3.1 mmHg | Standard Deviation 16.2 |
Primary
Changes From Baseline in Metabolic Syndrome Parameters (Total Cholesterol Level) at Final Assessment Point
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | Changes From Baseline in Metabolic Syndrome Parameters (Total Cholesterol Level) at Final Assessment Point | -9.0 mg/dL | Standard Deviation 39.3 |
Primary
Changes From Baseline in Metabolic Syndrome Parameters (Waist Circumference) at Final Assessment Point
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Changes From Baseline in Metabolic Syndrome Parameters (Waist Circumference) at Final Assessment Point | Male Participants | 0.51 cm | Standard Deviation 5.18 |
| Pioglitazone | Changes From Baseline in Metabolic Syndrome Parameters (Waist Circumference) at Final Assessment Point | Female Participants | 0.54 cm | Standard Deviation 6.06 |
Primary
Percentage of Participants Who Met at Least One New Cerebral and Cardiovascular Events
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone | Percentage of Participants Who Met at Least One New Cerebral and Cardiovascular Events | 1.01 Percentage of Participants |
Secondary
Association Between Patient Baseline Characteristics, Including Any Metabolic Syndrome-related Risk Factors, and Onset of New Cerebral and Cardiovascular Events
Time frame: 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.
Secondary
Changes From Baseline in HbA1c (NGSP) With Number of Metabolic Syndrome-related Risk Factor (MetS-related Factor) at Final Assessment Point
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | 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 |
| Pioglitazone | 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 |
| Pioglitazone | 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 |
| Pioglitazone | 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 |