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 use of pioglitazone/metformin hydrochloride combination tablets in the routine clinical setting in patients with type 2 diabetes mellitus for whom therapy with pioglitazone hydrochloride combined with metformin hydrochloride is considered suitable.
Detailed description
This is a special drug use surveillance (survey on long-term use) designed to investigate the safety and efficacy of long-term use of pioglitazone/metformin hydrochloride combination tablets (Metact Combination Tablets) in patients with type 2 diabetes mellitus in the routine clinical setting. The following items will also be studied: 1. The effects on safety and efficacy caused by changing the administration method of metformin hydrochloride associated with switching to Metact Combination Tablets 2. The effects on compliance associated with switching to Metact Combination Tablets 3. Safety and efficacy in patients who showed inadequate response to pioglitazone hydrochloride and were then switched to Metact Combination Tablets The planned sample size was 1000 participants. The usual adult dosage is one tablet of Metact administered orally once daily after breakfast (15 mg/500 mg or 30 mg/500 mg of pioglitazone/metformin hydrochloride). \<Precautions Related to Dosage and Administration\> Edema due to pioglitazone administration has been reported with comparative frequency in women. Therefore, it is preferable to be vigilant for edema and start Metact Combination Tablets at a dosage equivalent to 15 mg of pioglitazone once daily when administering the study drug to women.
Interventions
DRUGPioglitazone/metformin hydrochloride
Pioglitazone/metformin hydrochloride combination tablets
Sponsors
Takeda
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
-Patients with type 2 diabetes mellitus for whom a physician has concluded that therapy with pioglitazone hydrochloride combined with metformin hydrochloride is suitable and for whom long-term treatment with Metact Combination Tablets is considered necessary.
Exclusion criteria
-Patients for whom pioglitazone hydrochloride and metformin hydrochloride are contraindicated. 1. Patients with cardiac insufficiency or a history of cardiac insufficiency 2. Patients with the following conditions (i) Patients with a history of lactic acidosis (ii) Dialysis patients (including peritoneal dialysis) (iii) Patients with cardiovascular conditions such as shock, cardiac insufficiency, myocardial infarction, and pulmonary embolism; patients with severely impaired pulmonary function; and patients with other conditions fostering susceptibility to hypoxemia (iv) Patients with excessive alcohol consumption (v) Patients with dehydration (vi) Patients with gastrointestinal disorders such as diarrhea and vomiting (vii) Elderly patients 3. Patients with renal impairment (including mild renal impairment) 4. Patients with hepatic impairment 5. Patients with severe ketosis, diabetic coma or pre-coma, or type I diabetes mellitus 6. Patients with severe infection, severe trauma, or pre- and post-operative patients 7. Patients who are malnourished, starved, debilitated, or have pituitary gland insufficiency or adrenal gland insufficiency 8. Patients with a history of hypersensitivity to the ingredients in Metact Combination Tablets or biguanides 9. Pregnant or potentially pregnant women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Drug Reactions | 12 months | Adverse events 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. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline and Months 3, 6, 9, 12 and final assessment | Tabulation of the HbA1c test value and change at each test time point (test value at each test time point after baseline - test value at baseline). A negative change from Baseline indicates improvement. n=number of participants analyzed at each time point. Final assessment is defined as a cumulative assessment of Month 12 and Early Termination Visit data. |
| Change From Baseline in Fasting Blood Glucose | Baseline and Months 3, 6, 9, 12 and final assessment | Tabulation of fasting blood glucose test values and change at each test time point (test value at each test time point after baseline - test value at baseline). A negative change from Baseline indicates improvement. n=number of participants analyzed at each time point. Final assessment is defined as a cumulative assessment of Month 12 and Early Termination Visit data. |
| Change From Baseline in Fasting Insulin | Baseline and Months 3, 6, 9, 12 and final assessment | Tabulation of fasting insulin test values and change at each test time point (test value at each test time point after baseline - test value at baseline). A negative change from Baseline indicates improvement. n=number of participants analyzed at each time point. Final assessment is defined as a cumulative assessment of Month 12 and Early Termination Visit data. |
Participant flow
Recruitment details
Participants took part in the study at 196 investigative sites in Japan from July 2010 to November 2013 (N=1103).
Pre-assignment details
Patients with type 2 diabetes mellitus for whom a physician has concluded that therapy with pioglitazone hydrochloride combined with metformin hydrochloride is suitable and for whom long-term treatment with Metact Combination Tablets is considered necessary.
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone/Metformin Hydrochloride Pioglitazone/metformin hydrochloride combination tablets, orally, for 12 months as prescribed by the standard of care. | 1,067 |
| Total | 1,067 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Data Not Available | 30 |
| Overall Study | Lost to Follow-up | 6 |
Baseline characteristics
| Characteristic | Pioglitazone/Metformin Hydrochloride |
|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 12.01 |
| Age, Customized ≥20 to <30 years | 7 participants |
| Age, Customized <20 years | 0 participants |
| Age, Customized ≥30 to <40 years | 33 participants |
| Age, Customized ≥40 to <50 years | 91 participants |
| Age, Customized ≥50 to <60 years | 218 participants |
| Age, Customized ≥60 to <70 years | 347 participants |
| Age, Customized <65 years | 534 participants |
| Age, Customized ≥65 years | 533 participants |
| Age, Customized ≥70 to <80 years | 294 participants |
| Age, Customized ≥80 years | 77 participants |
| Alcohol History (Drinking Alcohol-Containing Beverages Nearly Every Day) No | 597 participants |
| Alcohol History (Drinking Alcohol-Containing Beverages Nearly Every Day) Unknown | 177 participants |
| Alcohol History (Drinking Alcohol-Containing Beverages Nearly Every Day) Yes | 293 participants |
| Body Mass Index (BMI) | 26.61 kg/m^2 STANDARD_DEVIATION 4.738 |
| Body Mass Index, Customized <18.5 kg/m^2 | 10 participants |
| Body Mass Index, Customized ≥18.5 to <25 kg/m^2 | 261 participants |
| Body Mass Index, Customized ≥25 to <30 kg/m^2 | 280 participants |
| Body Mass Index, Customized ≥30 kg/m^2 | 125 participants |
| Body Mass Index, Customized Unknown | 391 participants |
| Breakdown of Complications Allergic conditions | 84 participants |
| Breakdown of Complications Diabetic complications | 169 participants |
| Breakdown of Complications Heart or cerebrovascular diseases | 144 participants |
| Breakdown of Complications Lifestyle-related diseases (excluding DM) | 858 participants |
| Breakdown of Complications Liver diseases | 139 participants |
| Breakdown of Complications Malignant tumors | 10 participants |
| Breakdown of Complications Other | 349 participants |
| Breakdown of Complications Renal diseases | 9 participants |
| Compliance Status of Metformin (Within 3 Months Before Switching to Metact Combination Tablets) < 50% | 8 participants |
| Compliance Status of Metformin (Within 3 Months Before Switching to Metact Combination Tablets) ≥ 50% | 22 participants |
| Compliance Status of Metformin (Within 3 Months Before Switching to Metact Combination Tablets) ≥ 70% | 75 participants |
| Compliance Status of Metformin (Within 3 Months Before Switching to Metact Combination Tablets) ≥ 90% | 380 participants |
| Compliance Status of Metformin (Within 3 Months Before Switching to Metact Combination Tablets) Unknown | 3 participants |
| Compliance Status of Pioglitazone (Within 3 Months Before Switching to Metact Combination Tablets) < 50% | 6 participants |
| Compliance Status of Pioglitazone (Within 3 Months Before Switching to Metact Combination Tablets) ≥ 50% | 19 participants |
| Compliance Status of Pioglitazone (Within 3 Months Before Switching to Metact Combination Tablets) ≥ 70% | 142 participants |
| Compliance Status of Pioglitazone (Within 3 Months Before Switching to Metact Combination Tablets) ≥ 90% | 534 participants |
| Compliance Status of Pioglitazone (Within 3 Months Before Switching to Metact Combination Tablets) Unknown | 18 participants |
| Complications: Breakdown of Allergic Conditions Asthma bronchial | 33 participants |
| Complications: Breakdown of Allergic Conditions Dermatitis allergic | 11 participants |
| Complications: Breakdown of Allergic Conditions Pollinosis | 12 participants |
| Complications: Breakdown of Allergic Conditions Rhinitis allergic | 38 participants |
| Complications: Breakdown of Diabetic Complications Diabetic nephropathy | 81 participants |
| Complications: Breakdown of Diabetic Complications Diabetic neuropathy | 74 participants |
| Complications: Breakdown of Diabetic Complications Diabetic retinopathy | 56 participants |
| Complications: Breakdown of Heart or Cerebrovascular Diseases Angina pectoris | 55 participants |
| Complications: Breakdown of Heart or Cerebrovascular Diseases Cardiac failure | 17 participants |
| Complications: Breakdown of Heart or Cerebrovascular Diseases Cerebral infarction (including late effects) | 52 participants |
| Complications: Breakdown of Heart or Cerebrovascular Diseases Myocardial infarction | 9 participants |
| Complications: Breakdown of Lifestyle-Related Diseases (Excluding Diabetes Mellitus) Dyslipidaemia | 634 participants |
| Complications: Breakdown of Lifestyle-Related Diseases (Excluding Diabetes Mellitus) Hypertension | 656 participants |
| Complications: Breakdown of Lifestyle-Related Diseases (Excluding Diabetes Mellitus) Hyperuricaemia | 79 participants |
| Complications: Breakdown of Liver Diseases Chronic hepatitis | 17 participants |
| Complications: Breakdown of Liver Diseases Hepatic cirrhosis | 1 participants |
| Complications: Breakdown of Liver Diseases Hepatic steatosis | 107 participants |
| Complications: Breakdown of Liver Diseases Hepatitis alcoholic | 14 participants |
| Complications: Breakdown of Malignant Tumors Gastric cancer | 1 participants |
| Complications: Breakdown of Malignant Tumors Large intestine carcinoma | 4 participants |
| Complications: Breakdown of Renal Diseases Nephrotic syndrome | 2 participants |
| Complications: Breakdown of Renal Diseases Renal failure chronic | 4 participants |
| Daily dose in Pioglitazone monotherapy prior to dosing of Metact Combination Tablets ≤ 15 mg/day | 191 participants |
| Daily dose in Pioglitazone monotherapy prior to dosing of Metact Combination Tablets > 15 mg/day to ≤ 30 mg/day | 114 participants |
| Daily dose in Pioglitazone monotherapy prior to dosing of Metact Combination Tablets > 30 mg/day to ≤ 45 mg/day | 2 participants |
| Daily dose in Pioglitazone monotherapy prior to dosing of Metact Combination Tablets > 45 mg/day | 0 participants |
| Daily dose in Pioglitazone monotherapy prior to dosing of Metact Combination Tablets | 20.7 mg/day STANDARD_DEVIATION 7.6 |
| Daily dose in Pioglitazone monotherapy prior to switching to Metact Combination Tablets ≤ 15 mg/day of Pio to Metact HD | 13 participants |
| Daily dose in Pioglitazone monotherapy prior to switching to Metact Combination Tablets ≤ 15 mg/day of Pio to Metact LD | 178 participants |
| Daily dose in Pioglitazone monotherapy prior to switching to Metact Combination Tablets > 15 mg/day to ≤ 30 mg/day of Pio to Metact HD | 93 participants |
| Daily dose in Pioglitazone monotherapy prior to switching to Metact Combination Tablets > 15 mg/day to ≤ 30 mg/day of Pio to Metact LD | 21 participants |
| Daily dose in Pioglitazone monotherapy prior to switching to Metact Combination Tablets > 30 mg/day to ≤ 45 mg/day of Pio to Metact HD | 2 participants |
| Daily dose in Pioglitazone monotherapy prior to switching to Metact Combination Tablets > 30 mg/day to ≤ 45 mg/day of Pio to Metact LD | 0 participants |
| Daily dose in Pioglitazone monotherapy prior to switching to Metact Combination Tablets > 45 mg/day of Pio to Metact HD | 0 participants |
| Daily dose in Pioglitazone monotherapy prior to switching to Metact Combination Tablets > 45 mg/day of Pio to Metact LD | 0 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment ≥1500 to <2250 mg/day of Met to Metact HD | 10 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment ≥1500 to <2250 mg/day of Met to Metact LD | 12 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment ≥2250 mg/day of Met to Metact HD | 4 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment ≥2250 mg/day of Met to Metact LD | 2 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment <500 mg/day of Met to Metact HD | 6 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment ≤500 mg/day of Met to Metact HD | 61 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment <500 mg/day of Met to Metact LD | 19 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment ≤500 mg/day of Met to Metact LD | 193 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment ≥500 to <750 mg/day of Met to Metact HD | 55 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment >500 to ≤750 mg/day of Met to Metact HD | 37 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment ≥500 to <750 mg/day of Met to Metact LD | 174 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment >500 to ≤750 mg/day of Met to Metact LD | 124 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment >750 mg/day of Met to Metact HD | 26 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment >750 mg/day of Met to Metact LD | 45 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment ≥750 to <1500 mg/day of Met to Metact HD | 49 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment ≥750 to <1500 mg/day of Met to Metact LD | 155 participants |
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment Other | 2 participants |
| Daily Dose of Metformin Prior to Dosing of Metact Combination Tablets ≥ 1500 to < 2250 mg/day | 22 participants |
| Daily Dose of Metformin Prior to Dosing of Metact Combination Tablets ≥ 2250 mg/day | 6 participants |
| Daily Dose of Metformin Prior to Dosing of Metact Combination Tablets < 500 mg/day | 25 participants |
| Daily Dose of Metformin Prior to Dosing of Metact Combination Tablets ≤ 500 mg/day | 254 participants |
| Daily Dose of Metformin Prior to Dosing of Metact Combination Tablets > 500 mg/day | 234 participants |
| Daily Dose of Metformin Prior to Dosing of Metact Combination Tablets ≥ 500 to < 750 mg/day | 229 participants |
| Daily Dose of Metformin Prior to Dosing of Metact Combination Tablets > 500 to ≤ 750 mg/day | 163 participants |
| Daily Dose of Metformin Prior to Dosing of Metact Combination Tablets > 750 mg/day | 71 participants |
| Daily Dose of Metformin Prior to Dosing of Metact Combination Tablets ≥ 750 to < 1500 mg/day | 206 participants |
| Daily Dose of Metformin Prior to Dosing of Metact Combination Tablets | 681.4 mg/day STANDARD_DEVIATION 310.08 |
| Daily Dose of Pioglitazone Before Switching to Metact Combination Tablets,and Metact Dose Assignment ≤15 mg/day of Pio to Metact HD | 27 participants |
| Daily Dose of Pioglitazone Before Switching to Metact Combination Tablets,and Metact Dose Assignment ≤15 mg/day of Pio to Metact LD | 429 participants |
| Daily Dose of Pioglitazone Before Switching to Metact Combination Tablets,and Metact Dose Assignment >15 to ≤30 mg/day of Pio to Metact HD | 212 participants |
| Daily Dose of Pioglitazone Before Switching to Metact Combination Tablets,and Metact Dose Assignment >15 to ≤30 mg/day of Pio to Metact LD | 46 participants |
| Daily Dose of Pioglitazone Before Switching to Metact Combination Tablets,and Metact Dose Assignment >30 to ≤45 mg/day of Pio to Metact HD | 4 participants |
| Daily Dose of Pioglitazone Before Switching to Metact Combination Tablets,and Metact Dose Assignment >30 to ≤45 mg/day of Pio to Metact LD | 1 participants |
| Daily Dose of Pioglitazone Before Switching to Metact Combination Tablets,and Metact Dose Assignment >45 mg/day of Pio to Metact HD | 0 participants |
| Daily Dose of Pioglitazone Before Switching to Metact Combination Tablets,and Metact Dose Assignment >45 mg/day of Pio to Metact LD | 0 participants |
| Daily Dose of Pioglitazone Prior to Dosing of Metact Combination Tablets ≤ 15 mg/day | 456 participants |
| Daily Dose of Pioglitazone Prior to Dosing of Metact Combination Tablets > 15 to ≤ 30 mg/day | 258 participants |
| Daily Dose of Pioglitazone Prior to Dosing of Metact Combination Tablets > 30 to ≤ 45 mg/day | 5 participants |
| Daily Dose of Pioglitazone Prior to Dosing of Metact Combination Tablets > 45 mg/day | 0 participants |
| Daily Dose of Pioglitazone Prior to Dosing of Metact Combination Tablets | 20.5 mg/day STANDARD_DEVIATION 7.6 |
| Duration of Type 2 Diabetes | 7.5 years STANDARD_DEVIATION 6.59 |
| Duration of Type 2 Diabetes, Customized ≥10 years | 216 participants |
| Duration of Type 2 Diabetes, Customized ≥2 to <5 years | 168 participants |
| Duration of Type 2 Diabetes, Customized <2 years | 163 participants |
| Duration of Type 2 Diabetes, Customized ≥5 to <10 years | 183 participants |
| Duration of Type 2 Diabetes, Customized Unknown | 337 participants |
| Fasting blood glucose at the start of treatment with Metact Combination Tablets | 150.1 mg/dL STANDARD_DEVIATION 56.43 |
| Fasting insulin at the start of treatment with Metact Combination Tablets | 10.775 μU/dL STANDARD_DEVIATION 9.0804 |
| Frequency of daily dosing of Metformin prior to dosing of Metact Combination Tablets BID | 246 participants |
| Frequency of daily dosing of Metformin prior to dosing of Metact Combination Tablets Daily | 58 participants |
| Frequency of daily dosing of Metformin prior to dosing of Metact Combination Tablets TID or more | 184 participants |
| HbA1c (NGSP value) at the start of treatment with Metact Combination Tablets | 7.69 percentage of HbA1c STANDARD_DEVIATION 1.369 |
| Healthcare Category Inpatient | 6 participants |
| Healthcare Category Outpatient | 1049 participants |
| Healthcare Category Outpatient and Inpatient | 12 participants |
| History of Allergies No | 931 participants |
| History of Allergies Unknown | 41 participants |
| History of Allergies Yes | 95 participants |
| Participants with Fasting blood glucose at the start of treatment with Metact Combination Tablets < 126 mg/dL | 157 participants |
| Participants with Fasting blood glucose at the start of treatment with Metact Combination Tablets ≥ 126 to < 140 mg/dL | 75 participants |
| Participants with Fasting blood glucose at the start of treatment with Metact Combination Tablets ≥ 140 to < 160 mg/dL | 80 participants |
| Participants with Fasting blood glucose at the start of treatment with Metact Combination Tablets ≥ 160 mg/dL | 134 participants |
| Participants with Fasting blood glucose at the start of treatment with Metact Combination Tablets Unknown | 621 participants |
| Participants with Fasting insulin at the start of treatment with Metact Combination Tablets ≥ 100 μU/dL | 0 participants |
| Participants with Fasting insulin at the start of treatment with Metact Combination Tablets ≥ 10.0 μU/dL to < 50.0 μU/dL | 46 participants |
| Participants with Fasting insulin at the start of treatment with Metact Combination Tablets < 1.0 μU/dL | 0 participants |
| Participants with Fasting insulin at the start of treatment with Metact Combination Tablets ≥ 1.0 μU/dL to < 5.0 μU/dL | 24 participants |
| Participants with Fasting insulin at the start of treatment with Metact Combination Tablets ≥ 50.0 μU/dL to < 100.0 μU/dL | 1 participants |
| Participants with Fasting insulin at the start of treatment with Metact Combination Tablets ≥ 5.0 μU/dL to < 10.0 μU/dL | 25 participants |
| Participants with Fasting insulin at the start of treatment with Metact Combination Tablets Unknown | 971 participants |
| Participants with HbA1c (NGSP value) at the start of treatment with Metact Combination Tablets < 6.0% | 39 participants |
| Participants with HbA1c (NGSP value) at the start of treatment with Metact Combination Tablets ≥ 6.0% to < 7.0% | 270 participants |
| Participants with HbA1c (NGSP value) at the start of treatment with Metact Combination Tablets ≥ 7.0% to < 8.0% | 340 participants |
| Participants with HbA1c (NGSP value) at the start of treatment with Metact Combination Tablets ≥ 8.0% | 290 participants |
| Participants with HbA1c (NGSP value) at the start of treatment with Metact Combination Tablets Unknown | 128 participants |
| Pregnancy status (Females) Not pregnant | 450 participants |
| Pregnancy status (Females) Pregnant | 0 participants |
| Presence of Complications No | 132 participants |
| Presence of Complications Yes | 935 participants |
| Presence of Medical History No | 875 participants |
| Presence of Medical History Unknown | 49 participants |
| Presence of Medical History Yes | 143 participants |
| Rate of compliance with exercise regimen at the start of treatment with Metact Combination Tablets < 50% | 135 participants |
| Rate of compliance with exercise regimen at the start of treatment with Metact Combination Tablets ≥ 50% | 305 participants |
| Rate of compliance with exercise regimen at the start of treatment with Metact Combination Tablets ≥ 70% | 294 participants |
| Rate of compliance with exercise regimen at the start of treatment with Metact Combination Tablets ≥ 90% | 205 participants |
| Rate of compliance with exercise regimen at the start of treatment with Metact Combination Tablets Not assessed or compliance status is unknown | 128 participants |
| Rate of compliance with the diet regimen at the start of treatment with Metact Combination Tablets < 50% | 76 participants |
| Rate of compliance with the diet regimen at the start of treatment with Metact Combination Tablets ≥ 50% | 259 participants |
| Rate of compliance with the diet regimen at the start of treatment with Metact Combination Tablets ≥ 70% | 367 participants |
| Rate of compliance with the diet regimen at the start of treatment with Metact Combination Tablets ≥ 90% | 270 participants |
| Rate of compliance with the diet regimen at the start of treatment with Metact Combination Tablets Not assessed or compliance status is unknown | 95 participants |
| Response to pioglitazone in Pioglitazone monotherapy prior to dosing of Metact Combination Tablets Inadequate responders | 307 participants 7.6 |
| Response to pioglitazone in Pioglitazone monotherapy prior to dosing of Metact Combination Tablets Patients excluding inadequate responders | 74 participants |
| Response to pioglitazone in Pioglitazone monotherapy prior to dosing of Metact Combination Tablets Unknown | 61 participants |
| Sex: Female, Male Female | 450 Participants |
| Sex: Female, Male Male | 617 Participants |
| Smoking Classification Current smoker | 155 participants |
| Smoking Classification Ex-smoker | 196 participants |
| Smoking Classification Never smoked | 499 participants |
| Smoking Classification Unknown | 217 participants |
| Stages of Cardiac Failure (New York Heart Association [NYHA] Classification) Class I | 14 participants |
| Stages of Cardiac Failure (New York Heart Association [NYHA] Classification) Class II | 3 participants |
| Stages of Cardiac Failure (New York Heart Association [NYHA] Classification) Class III | 0 participants |
| Stages of Cardiac Failure (New York Heart Association [NYHA] Classification) Class IV | 0 participants |
| Status of Administration of Pioglitazone and Metformin Prior to Dosing of Metact Combination Tablets Metformin alone prior to dosing | 211 participants |
| Status of Administration of Pioglitazone and Metformin Prior to Dosing of Metact Combination Tablets Neither pioglitazone nor metformin prior to dosing | 137 participants |
| Status of Administration of Pioglitazone and Metformin Prior to Dosing of Metact Combination Tablets Pioglitazone alone prior to dosing | 442 participants |
| Status of Administration of Pioglitazone and Metformin Prior to Dosing of Metact Combination Tablets Pioglitazone plus metformin prior to dosing | 277 participants |
| Switch from metformin (> 500 mg/day) to Metact Combination Tablets No | 833 participants |
| Switch from metformin (> 500 mg/day) to Metact Combination Tablets Yes | 234 participants |
| Weight | 69.0 kg STANDARD_DEVIATION 15.36 |
| Weight, Customized <40 kg | 7 participants |
| Weight, Customized ≥40 to <50 kg | 48 participants |
| Weight, Customized ≥50 to <60 kg | 138 participants |
| Weight, Customized ≥60 to <70 kg | 193 participants |
| Weight, Customized ≥70 kg | 310 participants |
| Weight, Customized Unmeasured | 371 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 1,067 |
| serious Total, serious adverse events | 18 / 1,067 |
Outcome results
Primary
Number of Participants With Adverse Drug Reactions
Adverse events 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. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions.
Time frame: 12 months
Population: Safety Analysis Set, all patients for whom data was collected in case report forms, except those who were treated before the contract period, those who were enrolled after Day 15 of the start of treatment with Metact Combination Tablets, and those with missing data after treatment (missed visits).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Thyroid cancer | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Anaemia | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Insomnia | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Dizziness | 2 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Dysgeusia | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Right ventricular failure | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Dyspnoea exertional | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Abdominal distension | 2 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Constipation | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Nausea | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Hepatic function abnormal | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Cold sweat | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Myalgia | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Renal impairment | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Chest discomfort | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Face oedema | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Malaise | 2 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Oedema | 5 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Oedema peripheral | 11 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Cardiothoracic ratio increased | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Blood cholesterol increased | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Blood triglycerides increased | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Lipids abnormal | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Blood creatinine increased | 1 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Weight increased | 4 participants |
| Pioglitazone/Metformin Hydrochloride | Number of Participants With Adverse Drug Reactions | Heat illness | 1 participants |
Secondary
Change From Baseline in Fasting Blood Glucose
Tabulation of fasting blood glucose test values and change at each test time point (test value at each test time point after baseline - test value at baseline). A negative change from Baseline indicates improvement. n=number of participants analyzed at each time point. Final assessment is defined as a cumulative assessment of Month 12 and Early Termination Visit data.
Time frame: Baseline and Months 3, 6, 9, 12 and final assessment
Population: The analysis was performed in the efficacy assessment population (n=905).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Fasting Blood Glucose | Month 3 (n=311) | -14.0 mg/dL | Standard Deviation 41.98 |
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Fasting Blood Glucose | Month 6 (n=275) | -15.5 mg/dL | Standard Deviation 40.82 |
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Fasting Blood Glucose | Month 9 (n=29) | -11.7 mg/dL | Standard Deviation 43.16 |
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Fasting Blood Glucose | Month 12 (n=255) | -17.3 mg/dL | Standard Deviation 42.97 |
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Fasting Blood Glucose | Final Assessment (n=375) | -17.9 mg/dL | Standard Deviation 45.36 |
Secondary
Change From Baseline in Fasting Insulin
Tabulation of fasting insulin test values and change at each test time point (test value at each test time point after baseline - test value at baseline). A negative change from Baseline indicates improvement. n=number of participants analyzed at each time point. Final assessment is defined as a cumulative assessment of Month 12 and Early Termination Visit data.
Time frame: Baseline and Months 3, 6, 9, 12 and final assessment
Population: The analysis was performed in the efficacy assessment population (n=905).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Fasting Insulin | Month 3 (n=22) | -1.768 μU/dL | Standard Deviation 4.2928 |
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Fasting Insulin | Month 6 (n=46) | -2.374 μU/dL | Standard Deviation 7.0954 |
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Fasting Insulin | Month 9 (n=22) | -1.018 μU/dL | Standard Deviation 5.9072 |
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Fasting Insulin | Month 12 (n=51) | -2.524 μU/dL | Standard Deviation 9.426 |
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Fasting Insulin | Final Assessment (n=63) | -2.107 μU/dL | Standard Deviation 8.736 |
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Tabulation of the HbA1c test value and change at each test time point (test value at each test time point after baseline - test value at baseline). A negative change from Baseline indicates improvement. n=number of participants analyzed at each time point. Final assessment is defined as a cumulative assessment of Month 12 and Early Termination Visit data.
Time frame: Baseline and Months 3, 6, 9, 12 and final assessment
Population: The analysis was performed in the efficacy assessment population (n=905).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 3 (n=819) | -0.47 percentage of HbA1c | Standard Deviation 1.03 |
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 6 (n=761) | -0.53 percentage of HbA1c | Standard Deviation 1.142 |
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 9 (n=681) | -0.55 percentage of HbA1c | Standard Deviation 1.183 |
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 12 (n=670) | -0.60 percentage of HbA1c | Standard Deviation 1.19 |
| Pioglitazone/Metformin Hydrochloride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Final Assessment (n=896) | -0.58 percentage of HbA1c | Standard Deviation 1.182 |