Type 2 Diabetes Mellitus
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to investigate the safety and efficacy of long-term treatment with pioglitazone (Actos Tablets) in the routine clinical setting in combination with an insulin product in patients with type 2 diabetes mellitus who responded inadequately when using an insulin product in addition to diet therapy and exercise therapy.
Detailed description
This is a special drug use surveillance on long-term use of newly co-administered pioglitazone tablets (Actos Tablets) as part of routine medical care in patients with type 2 diabetes mellitus who have poorly controlled blood glucose when using an insulin product in addition to diet therapy and exercise therapy; this survey is designed to determine the safety and efficacy of long-term use of pioglitazone tablets (Actos Tablets) in the routine clinical setting in combination with an insulin product (the planned sample size, 1000.) The usual adult dosage is 15 mg of pioglitazone administered orally once daily before or after breakfast. Dose adjustment will be made according to gender, age, and symptoms with an upper limit of 30 mg.
Interventions
DRUGPioglitazone
Pioglitazone Tablets
Sponsors
Takeda
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Participants with type 2 diabetes mellitus assumed to have insulin resistance who responded inadequately when using an insulin product in addition to diet therapy and exercise therapy who meet the following criteria at enrollment. 1. Participants treated with an insulin product for at least 4 weeks 2. Participants who started Actos Tablets for the first time after the start of an insulin product 3. Participants likely to be available for a 52-week observation and evaluation after the start of co-administration of Actos Tablets
Exclusion criteria
Participants with contraindications to Actos Tables and insulin products treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience at Least One Adverse Drug Reactions (ADRs) | Up to Week 52 | ADRs are defined as 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 or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52) | — |
| Change From Baseline in Fasting Triglycerides | Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52) | — |
| Change From Baseline in Fasting Blood Glucose | Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52) | — |
| Change From Baseline in LDL Cholesterol | Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52) | — |
| Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Baseline, Week 52, and final assessment (up to Week 52) | Number of participants who received study drug and specific daily dose of insulin product during the survey was reported. Daily dose of insulin was categorized by \< 30 units, \>= 30 and \< 60 units, \>= 60 and \< 90 units, \>= 90 units at each time points. |
| Change From Baseline in HDL Cholesterol | Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52) | — |
Participant flow
Recruitment details
Participants took part in the study at 169 investigative sites in Japan, from 30-July-2009 to 30-June-2014.
Pre-assignment details
Participants with a historical diagnosis of type 2 diabetes mellitus who failed to respond adequately to treatment with insulin therapy were enrolled to receive pioglitazone 15 milligram (mg) - 30 mg for up to 12 months. Participants received interventions as part of routine medical care.
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care. | 1,035 |
| Total | 1,035 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Case report forms uncollected | 27 |
| Overall Study | Patient did not visit the study site | 1 |
| Overall Study | Protocol Violation | 4 |
Baseline characteristics
| Characteristic | Pioglitazone |
|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 12.09 |
| BMI | 25.45 kg/m^2 STANDARD_DEVIATION 4.336 |
| Body Weight | 65.849 kg STANDARD_DEVIATION 14.0584 |
| Concomitant Cardiac Disease Had Concomitant Cardiac Disease | 148 Participants |
| Concomitant Cardiac Disease Had No Concomitant Cardiac Disease | 887 Participants |
| Concomitant Hepatic Disease Had Concomitant Hepatic Disease | 126 Participants |
| Concomitant Hepatic Disease Had No Concomitant Hepatic Disease | 909 Participants |
| Concomitant Renal Disease Had Concomitant Renal Disease | 423 Participants |
| Concomitant Renal Disease Had No Concomitant Renal Disease | 612 Participants |
| Diabetic Complications Had Diabetic Complications | 633 Participants |
| Diabetic Complications Had No Diabetic Complications | 402 Participants |
| Diastolic Blood Pressure (DBP) | 73.7 mmHg STANDARD_DEVIATION 10.53 |
| Diet Therapy Not on Diet Therapy | 34 Participants |
| Diet Therapy On Diet Therapy | 1000 Participants |
| Diet Therapy Unknown | 1 Participants |
| Drinking Habits Current Drinker | 280 Participants |
| Drinking Habits Ex-Drinker | 77 Participants |
| Drinking Habits Never Drank | 661 Participants |
| Drinking Habits Unknown | 17 Participants |
| Duration of type 2 diabetes mellitus ≥ 10 years | 661 Participants |
| Duration of type 2 diabetes mellitus < 1 year | 27 Participants |
| Duration of type 2 diabetes mellitus ≥ 1 year < 5 years | 98 Participants |
| Duration of type 2 diabetes mellitus ≥ 5 years < 10 years | 199 Participants |
| Duration of type 2 diabetes mellitus Unknown | 50 Participants |
| Exercise Therapy Not on Exercise Therapy | 102 Participants |
| Exercise Therapy On Exercise Therapy | 932 Participants |
| Exercise Therapy Unknown | 1 Participants |
| Fasting Blood Glucose | 172.0 mg/dL STANDARD_DEVIATION 65.49 |
| Fasting Triglyceride | 156.5 mg/dL STANDARD_DEVIATION 133.21 |
| Haemoglobin A1c (HbA1c) [National Glycohemoglobin Standardization Program (NGSP)] | 8.72 Percent STANDARD_DEVIATION 1.449 |
| HDL Cholesterol | 55.92 mg/dL STANDARD_DEVIATION 17.205 |
| LDL Cholesterol | 111.46 mg/dL STANDARD_DEVIATION 28.418 |
| Medical Complications Had Presence of Medical Complications | 957 Participants |
| Medical Complications Had Presence of Medical No Complications | 78 Participants |
| Medical History Had No Presence of Medical History | 683 Participants |
| Medical History Had Presence of Medical History | 343 Participants |
| Medical History Unknown | 9 Participants |
| Predisposition to Hypersensitivity Had No Predisposition to Hypersensitivity | 983 Participants |
| Predisposition to Hypersensitivity Had Predisposition to Hypersensitivity | 48 Participants |
| Predisposition to Hypersensitivity Unknown | 4 Participants |
| Pregnancy Status Not pregnant | 477 Participants |
| Pregnancy Status Pregnant | 0 Participants |
| Region of Enrollment Japan | 1035 Participants |
| Serum creatinine (Enzymatic method) | 0.784 mg/dL STANDARD_DEVIATION 0.2853 |
| Sex: Female, Male Female | 477 Participants |
| Sex: Female, Male Male | 558 Participants |
| Smoking Habits Current Smoker | 162 Participants |
| Smoking Habits Ex-Smoker | 160 Participants |
| Smoking Habits Never Smoked | 687 Participants |
| Smoking Habits Unknown | 26 Participants |
| Systolic Blood Pressure (SBP) | 131.6 mmHg STANDARD_DEVIATION 15.17 |
| Urine albumin/Creatinine ratio | 169.616 mg/gCR STANDARD_DEVIATION 535.5513 |
| Urine protein (Qualitative) - | 501 Participants |
| Urine protein (Qualitative) ± | 140 Participants |
| Urine protein (Qualitative) ＋ | 101 Participants |
| Urine protein (Qualitative) 2＋ | 66 Participants |
| Urine protein (Qualitative) 3＋ | 30 Participants |
| Urine protein (Qualitative) Unknown/No measuremen | 197 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 303 / 1,035 |
| serious Total, serious adverse events | 11 / 1,035 |
Outcome results
Primary
Number of Participants Who Experience at Least One Adverse Drug Reactions (ADRs)
ADRs are defined as 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 or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug.
Time frame: Up to Week 52
Population: The safety analysis set was defined as all participants who were enrolled and completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pioglitazone | Number of Participants Who Experience at Least One Adverse Drug Reactions (ADRs) | 213 Participants |
Secondary
Change From Baseline in Fasting Blood Glucose
Time frame: Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52)
Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. Here number of participants analyzed was evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Change From Baseline in Fasting Blood Glucose | Change at Week 12 | -26.2 mg/dL | Standard Deviation 60.97 |
| Pioglitazone | Change From Baseline in Fasting Blood Glucose | Change at Week 24 | -23.9 mg/dL | Standard Deviation 60.55 |
| Pioglitazone | Change From Baseline in Fasting Blood Glucose | Change at Week 36 | -21.7 mg/dL | Standard Deviation 64.72 |
| Pioglitazone | Change From Baseline in Fasting Blood Glucose | Change at Week 52 | -21.4 mg/dL | Standard Deviation 65.47 |
| Pioglitazone | Change From Baseline in Fasting Blood Glucose | Change at Final Assessment | -23.8 mg/dL | Standard Deviation 69.96 |
Secondary
Change From Baseline in Fasting Triglycerides
Time frame: Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52)
Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. Here number of participants analyzed was evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Change From Baseline in Fasting Triglycerides | Change at Week 24 | -19.8 mg/dL | Standard Deviation 109.61 |
| Pioglitazone | Change From Baseline in Fasting Triglycerides | Change at Week 12 | -20.7 mg/dL | Standard Deviation 90.24 |
| Pioglitazone | Change From Baseline in Fasting Triglycerides | Change at Week 36 | -28.4 mg/dL | Standard Deviation 123.98 |
| Pioglitazone | Change From Baseline in Fasting Triglycerides | Change at Week 52 | -8.5 mg/dL | Standard Deviation 115.86 |
| Pioglitazone | Change From Baseline in Fasting Triglycerides | Change at Final Assessment | -16.6 mg/dL | Standard Deviation 128.17 |
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Time frame: Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52)
Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. Here number of participants analyzed was evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Week 12 | -0.62 Percent | Standard Deviation 1.024 |
| Pioglitazone | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Week 24 | -0.75 Percent | Standard Deviation 1.21 |
| Pioglitazone | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Week 36 | -0.77 Percent | Standard Deviation 1.192 |
| Pioglitazone | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Week 52 | -0.75 Percent | Standard Deviation 1.169 |
| Pioglitazone | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Final Assessment | -0.72 Percent | Standard Deviation 1.236 |
Secondary
Change From Baseline in HDL Cholesterol
Time frame: Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52)
Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. Here number of participants analyzed was evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Change From Baseline in HDL Cholesterol | Change at Week 12 | 3.32 mg/dL | Standard Deviation 8.898 |
| Pioglitazone | Change From Baseline in HDL Cholesterol | Change at Week 24 | 1.98 mg/dL | Standard Deviation 9.628 |
| Pioglitazone | Change From Baseline in HDL Cholesterol | Change at Week 36 | 1.79 mg/dL | Standard Deviation 9.868 |
| Pioglitazone | Change From Baseline in HDL Cholesterol | Change at Week 52 | 1.35 mg/dL | Standard Deviation 8.94 |
| Pioglitazone | Change From Baseline in HDL Cholesterol | Change at Final Assessment | 2.04 mg/dL | Standard Deviation 9.358 |
Secondary
Change From Baseline in LDL Cholesterol
Time frame: Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52)
Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. Here number of participants analyzed was evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Change From Baseline in LDL Cholesterol | Change at Week 12 | -0.96 mg/dL | Standard Deviation 22.788 |
| Pioglitazone | Change From Baseline in LDL Cholesterol | Change at Week 24 | -0.16 mg/dL | Standard Deviation 24.239 |
| Pioglitazone | Change From Baseline in LDL Cholesterol | Change at Week 36 | -0.68 mg/dL | Standard Deviation 26.594 |
| Pioglitazone | Change From Baseline in LDL Cholesterol | Change at Week 52 | -0.33 mg/dL | Standard Deviation 25.258 |
| Pioglitazone | Change From Baseline in LDL Cholesterol | Change at Final Assessment | -0.82 mg/dL | Standard Deviation 25.908 |
Secondary
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points
Number of participants who received study drug and specific daily dose of insulin product during the survey was reported. Daily dose of insulin was categorized by \< 30 units, \>= 30 and \< 60 units, \>= 60 and \< 90 units, \>= 90 units at each time points.
Time frame: Baseline, Week 52, and final assessment (up to Week 52)
Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. Here number of participants analyzed was evaluable for this outcome measure.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Pioglitazone | Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Final Assessment | >= 30 and < 60 units of insulin product | 363 Participants |
| Pioglitazone | Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Final Assessment | >= 60 and < 90 units of insulin product | 72 Participants |
| Pioglitazone | Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Week 52 | < 30 units of insulin product | 379 Participants |
| Pioglitazone | Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Week 52 | >= 30 and < 60 units of insulin product | 256 Participants |
| Pioglitazone | Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Week 52 | >= 60 and < 90 units of insulin product | 52 Participants |
| Pioglitazone | Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Week 52 | >= 90 units of insulin product | 10 Participants |
| Pioglitazone | Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Final Assessment | < 30 units of insulin product | 532 Participants |
| Pioglitazone | Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Final Assessment | >= 90 units of insulin product | 15 Participants |
| Pioglitazone | Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Baseline | < 30 units of insulin product | 510 Participants |
| Pioglitazone | Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Baseline | >= 30 and < 60 units of insulin product | 359 Participants |
| Pioglitazone | Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Baseline | >= 60 and < 90 units of insulin product | 68 Participants |
| Pioglitazone | Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points | Baseline | >= 90 units of insulin product | 16 Participants |