Type 2 Diabetes
Conditions
Keywords
Pharmacological therapy
Brief summary
The purpose of this study is to evaluate the safety and efficacy of long-term use of pioglitazone/glimepiride combination tablets (Sonias Combination Tablets LD) in patients with type 2 diabetes mellitus who respond poorly to pioglitazone hydrochloride monotherapy (pioglitazone at 15 mg/day) in the routine clinical setting.
Detailed description
This is a special drug use surveillance on long-term use of pioglitazone/glimepiride combination tablets (Sonias Combination Tablets LD) designed to investigate the frequency of adverse drug reactions in patients with type 2 diabetes mellitus who respond poorly to pioglitazone hydrochloride monotherapy (pioglitazone at 15 mg/day). The usual adult dosage is one tablet (15 mg/1 mg of pioglitazone/glimepiride) administered orally once daily before or after breakfast.
Interventions
Pioglitazone/glimepiride 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 treatment with pioglitazone hydrochloride monotherapy (pioglitazone at 15 mg/day) is considered inefficacious as per physician's assessment and for whom long-term treatment with pioglitazone/glimepiride combination tablets is considered necessary
Exclusion criteria
* (1) Patients with cardiac failure or a history of cardiac failure (2) Patients with serious hepatic or renal impairment (3) Patients with severe ketosis, diabetic coma or precoma, or type 1 diabetes mellitus (4) Patients with severe infection, severe trauma, or pre- and post-operative patients (5) Patients with gastrointestinal disorders such as diarrhea and vomiting (6) Pregnant or potentially pregnant women (7) Patients with a history of hypersensitivity to the ingredients in Sonias Combination Tablets or sulfonamides
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Drug Reactions | 12 months | Frequency of adverse drug reactions is defined as the number of participants with adverse drug reactions. Frequency, seriousness, and time to onset of adverse drug reactions were tabulated by each symptom. 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. |
| Frequency of Serious Adverse Drug Reactions | 12 months | Frequency of serious adverse drug reactions is defined at the number of participants with serious adverse drug reactions. Frequency of serious adverse drug reactions were tabulated by each symptom. 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. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. 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, Months 3, 6, 9, 12 and at Final assessment | Tabulation of HbA1c values and the changes from Baseline 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. |
| Change From Baseline in Fasting Blood Glucose Level | Baseline, Months 3, 6, 9, 12 and at Final assessment | Tabulation of fasting blood glucose level and the changes from Baseline 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. |
| Change From Baseline in Fasting Insulin Level | Baseline, Months 3, 6, 9, 12 and at Final assessment | Tabulation of fasting insulin level and the changes from Baseline 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. A positive change from Baseline indicates a worsening. |
Participant flow
Recruitment details
This observational study took part at 64 investigative sites in Japan from 15 June 2011 to 31 July 2014.
Pre-assignment details
Participants with a diagnosis of type 2 diabetes mellitus receiving treatment with pioglitazone/glimepiride 15 mg/1 mg once daily in routine clinical practice, because pioglitazone alone was not considered effective, were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone/Glimepiride Pioglitazone/glimepiride 15 mg/1 mg, orally once daily before or after breakfast. | 289 |
| Total | 289 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Changes of Investigator | 2 |
| Overall Study | Data Not Available After Treatment | 1 |
| Overall Study | Enrolled 15 Days After the First Dose | 1 |
| Overall Study | Other Miscellaneous Reasons | 1 |
Baseline characteristics
| Characteristic | Pioglitazone/Glimepiride |
|---|---|
| Age, Continuous | 65.8 years STANDARD_DEVIATION 12.56 |
| Age, Customized <65 years | 112 participants |
| Age, Customized ≥65 years | 177 participants |
| BMI, Categorical <18.5 kg/m^2 | 8 participants |
| BMI, Categorical ≥18.5 to <25 kg/m^2 | 107 participants |
| BMI, Categorical ≥25 to <30 kg/m^2 | 97 participants |
| BMI, Categorical ≥30 kg/m^2 | 30 participants |
| BMI, Categorical Unknown | 47 participants |
| Body Mass Index (BMI) | 25.45 kg/m^2 STANDARD_DEVIATION 4.23 |
| Breakdown of Complications (Tabulated in Duplicate) Cerebrovascular disease | 15 participants |
| Breakdown of Complications (Tabulated in Duplicate) Diabetic nephropathy | 17 participants |
| Breakdown of Complications (Tabulated in Duplicate) Diabetic neuropathy | 12 participants |
| Breakdown of Complications (Tabulated in Duplicate) Diabetic retinopathy | 9 participants |
| Breakdown of Complications (Tabulated in Duplicate) Dyslipidaemia | 175 participants |
| Breakdown of Complications (Tabulated in Duplicate) Heart disease | 17 participants |
| Breakdown of Complications (Tabulated in Duplicate) Hypertension | 175 participants |
| Breakdown of Complications (Tabulated in Duplicate) Hyperuricaemia | 29 participants |
| Breakdown of Complications (Tabulated in Duplicate) Liver disease | 25 participants |
| Breakdown of Complications (Tabulated in Duplicate) Malignant tumor | 1 participants |
| Breakdown of Complications (Tabulated in Duplicate) Microangiopathy | 31 participants |
| Breakdown of Complications (Tabulated in Duplicate) Other | 12 participants |
| Breakdown of Complications (Tabulated in Duplicate) Renal disease | 18 participants |
| Categories of Health Care Inpatient | 2 participants |
| Categories of Health Care Outpatient | 287 participants |
| Compliance Rate with the Diet Regimen (at the Start of Treatment with Sonias Combination Tablets LD) < 50% | 18 participants |
| Compliance Rate with the Diet Regimen (at the Start of Treatment with Sonias Combination Tablets LD) ≥ 50% | 53 participants |
| Compliance Rate with the Diet Regimen (at the Start of Treatment with Sonias Combination Tablets LD) ≥ 70% | 118 participants |
| Compliance Rate with the Diet Regimen (at the Start of Treatment with Sonias Combination Tablets LD) ≥ 90% | 73 participants |
| Compliance Rate with the Diet Regimen (at the Start of Treatment with Sonias Combination Tablets LD) Not performed or compliance status is unknown | 27 participants |
| Compliance Rate with the Exercise Regimen (at Start of Treatment with Sonias Combination Tablets LD) < 50% | 36 participants |
| Compliance Rate with the Exercise Regimen (at Start of Treatment with Sonias Combination Tablets LD) ≥ 50% | 76 participants |
| Compliance Rate with the Exercise Regimen (at Start of Treatment with Sonias Combination Tablets LD) ≥ 70% | 97 participants |
| Compliance Rate with the Exercise Regimen (at Start of Treatment with Sonias Combination Tablets LD) ≥ 90% | 49 participants |
| Compliance Rate with the Exercise Regimen (at Start of Treatment with Sonias Combination Tablets LD) Not performed or compliance status is unknown | 31 participants |
| Complications of Type 2 Diabetes No | 25 participants |
| Complications of Type 2 Diabetes Yes | 264 participants |
| Duration of Type 2 Diabetes | 6.19 years STANDARD_DEVIATION 5.444 |
| Duration of Type 2 Diabetes, Categorical ≥10 years | 49 participants |
| Duration of Type 2 Diabetes, Categorical ≥2 to <5 years | 44 participants |
| Duration of Type 2 Diabetes, Categorical <2 years | 56 participants |
| Duration of Type 2 Diabetes, Categorical ≥5 to <10 years | 58 participants |
| Duration of Type 2 Diabetes, Categorical Unknown | 82 participants |
| Glycosylated hemoglobin A1c (HbA1c) (at Start of Treatment with Sonias Combination Tablets LD) | 7.75 % STANDARD_DEVIATION 1.493 |
| HbA1c, Categorical < 6.0% | 8 participants |
| HbA1c, Categorical ≥ 6.0% to < 7.0% | 66 participants |
| HbA1c, Categorical ≥ 7.0% to < 8.0% | 110 participants |
| HbA1c, Categorical ≥ 8.0% | 80 participants |
| HbA1c, Categorical Unknown | 25 participants |
| History of Alcohol (Drinking Alcohol-Containing Beverages Nearly Every Day) No | 81 participants |
| History of Alcohol (Drinking Alcohol-Containing Beverages Nearly Every Day) Unknown | 41 participants |
| History of Alcohol (Drinking Alcohol-Containing Beverages Nearly Every Day) Yes | 167 participants |
| History of Allergy No | 239 participants |
| History of Allergy Unknown | 21 participants |
| History of Allergy Yes | 29 participants |
| Pregnancy Status (Females Only) Not pregnant | 117 participants |
| Pregnancy Status (Females Only) Pregnant | 0 participants |
| Presence of Medical History No | 228 participants |
| Presence of Medical History Unknown | 22 participants |
| Presence of Medical History Yes | 39 participants |
| Sex: Female, Male Female | 117 Participants |
| Sex: Female, Male Male | 172 Participants |
| Smoking Classification Current Smoker | 54 participants |
| Smoking Classification Ex-smoker | 55 participants |
| Smoking Classification Never Smoked | 134 participants |
| Smoking Classification Unknown | 46 participants |
| Weight | 65.64 kg STANDARD_DEVIATION 13.662 |
| Weight, Categorical <40 kg | 1 participants |
| Weight, Categorical ≥40 to <50 kg | 24 participants |
| Weight, Categorical ≥50 to <60 kg | 57 participants |
| Weight, Categorical ≥60 to <70 kg | 81 participants |
| Weight, Categorical ≥70 kg | 87 participants |
| Weight, Categorical Unmeasured | 39 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 289 |
| serious Total, serious adverse events | 2 / 289 |
Outcome results
Primary
Frequency of Adverse Drug Reactions
Frequency of adverse drug reactions is defined as the number of participants with adverse drug reactions. Frequency, seriousness, and time to onset of adverse drug reactions were tabulated by each symptom. 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: The Safety Analysis Set (safety assessment population) included all patients who received at least one dose of pioglitazone/glimepiride (N=289).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pioglitazone/Glimepiride | Frequency of Adverse Drug Reactions | Anaemia | 1 participants |
| Pioglitazone/Glimepiride | Frequency of Adverse Drug Reactions | Hypoglycaemia | 7 participants |
| Pioglitazone/Glimepiride | Frequency of Adverse Drug Reactions | Generalised oedema | 1 participants |
| Pioglitazone/Glimepiride | Frequency of Adverse Drug Reactions | Oedema | 1 participants |
| Pioglitazone/Glimepiride | Frequency of Adverse Drug Reactions | Weight increased | 6 participants |
Primary
Frequency of Serious Adverse Drug Reactions
Frequency of serious adverse drug reactions is defined at the number of participants with serious adverse drug reactions. Frequency of serious adverse drug reactions were tabulated by each symptom. 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. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions.
Time frame: 12 months
Population: The Safety Analysis Set (safety assessment population) included all patients who received at least one dose of pioglitazone/glimepiride (N=289).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone/Glimepiride | Frequency of Serious Adverse Drug Reactions | 0 participants |
Secondary
Change From Baseline in Fasting Blood Glucose Level
Tabulation of fasting blood glucose level and the changes from Baseline 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.
Time frame: Baseline, Months 3, 6, 9, 12 and at Final assessment
Population: The analysis was performed on the efficacy assessment population (N=250) with data available at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Blood Glucose Level | Month 3 (n=76) | -15.9 mg/dL | Standard Deviation 35.99 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Blood Glucose Level | Month 6 (n=59) | -23.2 mg/dL | Standard Deviation 40.11 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Blood Glucose Level | Month 9 (n=53) | -12.7 mg/dL | Standard Deviation 37.6 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Blood Glucose Level | Month 12 (n=28) | -17.0 mg/dL | Standard Deviation 20.42 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Blood Glucose Level | Final Assessment (n=83) | -17.7 mg/dL | Standard Deviation 42.23 |
Secondary
Change From Baseline in Fasting Insulin Level
Tabulation of fasting insulin level and the changes from Baseline 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. A positive change from Baseline indicates a worsening.
Time frame: Baseline, Months 3, 6, 9, 12 and at Final assessment
Population: The analysis was performed on the efficacy assessment population (N=250) with data available at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Insulin Level | Month 6 (n=25) | -0.25 μU/dL | Standard Deviation 3.976 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Insulin Level | Month 3 (n=33) | 1.66 μU/dL | Standard Deviation 9.419 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Insulin Level | Month 9 (n=17) | 1.32 μU/dL | Standard Deviation 3.949 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Insulin Level | Month 12 (n=15) | -0.29 μU/dL | Standard Deviation 3.489 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Insulin Level | Final Assessment (n=39) | 0.98 μU/dL | Standard Deviation 7.31 |
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Tabulation of HbA1c values and the changes from Baseline 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.
Time frame: Baseline, Months 3, 6, 9, 12 and at Final assessment
Population: The analysis was performed on the efficacy assessment population (N=250) with data available at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone/Glimepiride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 6 (n=190) | -0.84 percent | Standard Deviation 1.094 |
| Pioglitazone/Glimepiride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 3 (n=234) | -0.83 percent | Standard Deviation 1.03 |
| Pioglitazone/Glimepiride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 9 (n=177) | -0.83 percent | Standard Deviation 1.088 |
| Pioglitazone/Glimepiride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 12 (n=84) | -0.62 percent | Standard Deviation 1.139 |
| Pioglitazone/Glimepiride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Final Assessment (n=247) | -0.92 percent | Standard Deviation 1.285 |