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 Sonias Combination Tablets in patients with type 2 diabetes mellitus in the routine clinical setting.
Detailed description
This a special drug use surveillance on long-term use of pioglitazone/glimepiride combination tablets (Sonias Combination Tablets) designed to investigate the frequency of adverse drug reactions in patients with type 2 diabetes mellitus in the routine clinical setting. The usual adult dosage is one tablet of Sonias administered orally once daily before or after breakfast (15 mg/1 mg or 30 mg/3 mg of pioglitazone/glimepiride).
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 a physician has concluded that combination therapy with pioglitazone hydrochloride and glimepiride is appropriate and for whom long-term treatment with Sonias 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 |
|---|---|---|
| Number of Participants With Adverse Drug Reactions | For 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 |
|---|---|---|
| Glycosylated Hemoglobin (HbA1c) | Baseline, and Months 3, 6, 9, 12 and at Final Assessment | Tabulated glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each test time point or final visit relative to baseline. |
| Change From Baseline in Fasting Blood Glucose Level | Baseline, Months 3, 6, 9, 12 and at Final Assessment | Tabulated the changes from baseline in fasting blood glucose level 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 Glycosylated Hemoglobin (HbA1c) | Baseline, and Months 3, 6, 9, 12 and at Final Assessment | Tabulated the changes from baseline in glycosylated hemoglobin (HbA1c) values 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 | Tabulated 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. |
| Fasting Insulin Level | Baseline, Months 3, 6, 9, 12 and at Final Assessment | Tabulated fasting insulin level at each test time point. |
| Fasting Blood Glucose Level | Baseline, Months 3, 6, 9, 12 and at Final Assessment | Tabulated fasting blood glucose level from baseline at each test time point. |
Participant flow
Recruitment details
Participants took part in the study at 182 investigative sites in Japan from 15 June 2011 to 31 May 2014.
Pre-assignment details
Participants with a historical diagnosis of type 2 diabetes mellitus for whom therapy with pioglitazone combined with glimepiride is suitable and long-term treatment is considered necessary were enrolled in one treatment group to receive pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone/Glimepiride Pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast. | 1,158 |
| Total | 1,158 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Data Not Available | 5 |
| Overall Study | Lost to Follow-up | 5 |
Baseline characteristics
| Characteristic | Pioglitazone/Glimepiride |
|---|---|
| Age, Continuous | 64.9 years STANDARD_DEVIATION 12.14 |
| Age, Customized ≥65 to <74 years | 354 participants |
| Age, Customized <65 years | 539 participants |
| Age, Customized ≥65 years | 619 participants |
| Age, Customized ≥75 years | 265 participants |
| Alcohol History (Drinking Alcohol-Containing Beverages Most Days) No | 375 participants |
| Alcohol History (Drinking Alcohol-Containing Beverages Most Days) Unknown | 187 participants |
| Alcohol History (Drinking Alcohol-Containing Beverages Most Days) Yes | 596 participants |
| BMI Categorical <18.5 kg/m^2 | 12 participants |
| BMI Categorical ≥18.5 to <25 kg/m^2 | 422 participants |
| BMI Categorical ≥25 to <30 kg/m^2 | 412 participants |
| BMI Categorical ≥30 kg/m^2 | 165 participants |
| BMI Categorical Unknown | 147 participants |
| Body Mass Index (BMI) | 26.19 kg/m^2 STANDARD_DEVIATION 4.401 |
| Breakdown of Complications Cerebrovascular disease | 76 participants |
| Breakdown of Complications Diabetic nephropathy | 144 participants |
| Breakdown of Complications Diabetic neuropathy | 88 participants |
| Breakdown of Complications Diabetic retinopathy | 71 participants |
| Breakdown of Complications Dyslipidaemia | 787 participants |
| Breakdown of Complications Heart disease | 134 participants |
| Breakdown of Complications Hypertension | 723 participants |
| Breakdown of Complications Hyperuricaemia | 95 participants |
| Breakdown of Complications Liver disease | 154 participants |
| Breakdown of Complications Malignant tumor | 10 participants |
| Breakdown of Complications Microangiopathy | 227 participants |
| Breakdown of Complications Other | 19 participants |
| Breakdown of Complications Renal disease | 159 participants |
| Compliance Rate with the Diet Regimen (At the Start of Treatment) < 50% | 91 participants |
| Compliance Rate with the Diet Regimen (At the Start of Treatment) ≥ 50% | 286 participants |
| Compliance Rate with the Diet Regimen (At the Start of Treatment) ≥ 70% | 371 participants |
| Compliance Rate with the Diet Regimen (At the Start of Treatment) ≥ 90% | 285 participants |
| Compliance Rate with the Diet Regimen (At the Start of Treatment) Undone or compliance status is unknown | 125 participants |
| Compliance rate with the Exercise Regimen (At the Start of Treatment) < 50% | 147 participants |
| Compliance rate with the Exercise Regimen (At the Start of Treatment) ≥ 50% | 348 participants |
| Compliance rate with the Exercise Regimen (At the Start of Treatment) ≥ 70% | 279 participants |
| Compliance rate with the Exercise Regimen (At the Start of Treatment) ≥ 90% | 219 participants |
| Compliance rate with the Exercise Regimen (At the Start of Treatment) Undone or compliance status is unknown | 165 participants |
| Duration of Type 2 Diabetes | 9.12 years STANDARD_DEVIATION 8.188 |
| Duration of Type 2 Diabetes, Categorical ≥10 years | 274 participants |
| Duration of Type 2 Diabetes, Categorical ≥2 to <5 years | 160 participants |
| Duration of Type 2 Diabetes, Categorical <2 years | 92 participants |
| Duration of Type 2 Diabetes, Categorical ≥5 to <10 years | 262 participants |
| Duration of Type 2 Diabetes, Categorical Unknown | 370 participants |
| Glycosylated Haemoglobin (HbA1c) at the Start of Study Treatment < 6.0% | 35 participants |
| Glycosylated Haemoglobin (HbA1c) at the Start of Study Treatment ≥ 6.0% to < 7.0% | 274 participants |
| Glycosylated Haemoglobin (HbA1c) at the Start of Study Treatment ≥ 7.0% to < 8.0% | 427 participants |
| Glycosylated Haemoglobin (HbA1c) at the Start of Study Treatment ≥ 8.0% | 355 participants |
| Glycosylated Haemoglobin (HbA1c) at the Start of Study Treatment Unknown | 67 participants |
| HbA1c at the Start of Study Treatment | 7.71 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.313 |
| Healthcare Category Inpatient | 3 participants |
| Healthcare Category Outpatient | 1155 participants |
| History of Allergies No | 959 participants |
| History of Allergies Unknown | 118 participants |
| History of Allergies Yes | 81 participants |
| Pregnancy Status <Females> Not pregnant | 439 participants |
| Pregnancy Status <Females> Pregnant | 0 participants |
| Presence of Complications No | 108 participants |
| Presence of Complications Yes | 1050 participants |
| Presence of Medical History No | 897 participants |
| Presence of Medical History Unknown | 104 participants |
| Presence of Medical History Yes | 157 participants |
| Sex: Female, Male Female | 439 Participants |
| Sex: Female, Male Male | 719 Participants |
| Smoking Classification Current Smoker | 191 participants |
| Smoking Classification Ex-smoker | 228 participants |
| Smoking Classification Never Smoked | 516 participants |
| Smoking Classification Unknown | 223 participants |
| Timing of Initiation of Glimepiride Before the Start of Study Treatment < 3 months | 42 participants |
| Timing of Initiation of Glimepiride Before the Start of Study Treatment ≥ 3 months | 223 participants |
| Timing of Initiation of Glimepiride Before the Start of Study Treatment Unknown | 73 participants |
| Timing of Initiation of Pioglitazone and Glimepiride Before the Start of Study Treatment ≥ 3 months | 347 participants |
| Timing of Initiation of Pioglitazone and Glimepiride Before the Start of Study Treatment Other | 60 participants |
| Timing of Initiation of Pioglitazone and Glimepiride Before the Start of Study Treatment Unknown | 151 participants |
| Timing of Initiation of Pioglitazone Before the Start of Study Treatment < 3 months | 17 participants |
| Timing of Initiation of Pioglitazone Before the Start of Study Treatment ≥ 3 months | 104 participants |
| Timing of Initiation of Pioglitazone Before the Start of Study Treatment Unknown | 68 participants |
| Weight | 67.86 kg STANDARD_DEVIATION 14.281 |
| Weight Categorical <40 kg | 7 participants |
| Weight Categorical ≥40 to <50 kg | 74 participants |
| Weight Categorical ≥50 to <60 kg | 223 participants |
| Weight Categorical ≥60 to <70 kg | 327 participants |
| Weight Categorical ≥70 kg | 427 participants |
| Weight Categorical Unmeasured | 100 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 1,158 |
| serious Total, serious adverse events | 23 / 1,158 |
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: For 12 months
Population: All enrolled participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Hypoglycaemia | 13 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Dizziness | 4 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Dysgeusia | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Headache | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Hypoaesthesia | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Cardiac failure | 2 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Cardiac failure congestive | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Pleural effusion | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Eructation | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Nausea | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Cholelithiasis | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Drug eruption | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Pruritus | 2 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Swelling face | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Urticaria | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Face oedema | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Feeling abnormal | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Hunger | 2 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Oedema | 7 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Oedema peripheral | 4 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Sudden death | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Blood creatine phosphokinase increased | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Alanine aminotransferase increased | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Blood triglycerides increased | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Blood glucose decreased | 1 participants |
| Pioglitazone/Glimepiride | Number of Participants With Adverse Drug Reactions | Weight increased | 8 participants |
Secondary
Change From Baseline in Fasting Blood Glucose Level
Tabulated the changes from baseline in fasting blood glucose level 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: All enrolled participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Blood Glucose Level | Month 3 (n=331) | -16.7 mg/dL | Standard Deviation 44.39 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Blood Glucose Level | Month 6 (n=287) | -14.3 mg/dL | Standard Deviation 48.17 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Blood Glucose Level | Month 9 (n=273) | -15.7 mg/dL | Standard Deviation 45.94 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Blood Glucose Level | Month 12 (n=462) | -12.5 mg/dL | Standard Deviation 45.5 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Blood Glucose Level | Final Assessment (n=369) | -16.4 mg/dL | Standard Deviation 47.41 |
Secondary
Change From Baseline in Fasting Insulin Level
Tabulated 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: All enrolled participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Insulin Level | Month 3 (n=39) | -0.24 μU/dL | Standard Deviation 1.376 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Insulin Level | Month 6 (n=32) | 0.02 μU/dL | Standard Deviation 1.163 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Insulin Level | Month 9 (n=30) | -0.60 μU/dL | Standard Deviation 2.121 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Insulin Level | Month 12 (n=18) | 0.58 μU/dL | Standard Deviation 2.582 |
| Pioglitazone/Glimepiride | Change From Baseline in Fasting Insulin Level | Final Assessment (n=46) | -0.01 μU/dL | Standard Deviation 2.397 |
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Tabulated the changes from baseline in glycosylated hemoglobin (HbA1c) values 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, and Months 3, 6, 9, 12 and at Final Assessment
Population: All enrolled participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone/Glimepiride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 3 (n=1016) | -0.45 percentage of glycosylated haemoglobin | Standard Deviation 0.936 |
| Pioglitazone/Glimepiride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 6 (n=893) | -0.55 percentage of glycosylated haemoglobin | Standard Deviation 1.144 |
| Pioglitazone/Glimepiride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 9 (n=831) | -0.56 percentage of glycosylated haemoglobin | Standard Deviation 1.107 |
| Pioglitazone/Glimepiride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 12 (n=462) | -0.57 percentage of glycosylated haemoglobin | Standard Deviation 1.196 |
| Pioglitazone/Glimepiride | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Final Assessment (n=1,054) | -0.57 percentage of glycosylated haemoglobin | Standard Deviation 1.152 |
Secondary
Fasting Blood Glucose Level
Tabulated fasting blood glucose level from baseline at each test time point.
Time frame: Baseline, Months 3, 6, 9, 12 and at Final Assessment
Population: All enrolled participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone/Glimepiride | Fasting Blood Glucose Level | At the start of treatment (n=369) | 147.2 mg/dL | Standard Deviation 51.87 |
| Pioglitazone/Glimepiride | Fasting Blood Glucose Level | Month 3 (n=331) | 130.2 mg/dL | Standard Deviation 43.18 |
| Pioglitazone/Glimepiride | Fasting Blood Glucose Level | Month 6 (n=287) | 131.7 mg/dL | Standard Deviation 41.09 |
| Pioglitazone/Glimepiride | Fasting Blood Glucose Level | Month 9 (n=273) | 129.2 mg/dL | Standard Deviation 36.71 |
| Pioglitazone/Glimepiride | Fasting Blood Glucose Level | Month 12 (n=462) | 126.8 mg/dL | Standard Deviation 42.01 |
| Pioglitazone/Glimepiride | Fasting Blood Glucose Level | Final Assessment (n=369) | 130.9 mg/dL | Standard Deviation 46.82 |
Secondary
Fasting Insulin Level
Tabulated fasting insulin level at each test time point.
Time frame: Baseline, Months 3, 6, 9, 12 and at Final Assessment
Population: All enrolled participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone/Glimepiride | Fasting Insulin Level | At the start of treatment (n=46) | 5.78 μU/dL | Standard Deviation 2.88 |
| Pioglitazone/Glimepiride | Fasting Insulin Level | Month 9 (n=30) | 5.40 μU/dL | Standard Deviation 2.642 |
| Pioglitazone/Glimepiride | Fasting Insulin Level | Month 12 (n=18) | 6.57 μU/dL | Standard Deviation 3.789 |
| Pioglitazone/Glimepiride | Fasting Insulin Level | Month 3 (n=39) | 5.38 μU/dL | Standard Deviation 2.885 |
| Pioglitazone/Glimepiride | Fasting Insulin Level | Month 6 (n=32) | 5.48 μU/dL | Standard Deviation 2.964 |
| Pioglitazone/Glimepiride | Fasting Insulin Level | Final Assessment (n=46) | 5.77 μU/dL | Standard Deviation 3.238 |
Secondary
Glycosylated Hemoglobin (HbA1c)
Tabulated glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each test time point or final visit relative to baseline.
Time frame: Baseline, and Months 3, 6, 9, 12 and at Final Assessment
Population: All enrolled participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone/Glimepiride | Glycosylated Hemoglobin (HbA1c) | At the start of treatment (n=1054) | 7.70 percentage of glycosylated haemoglobin | Standard Deviation 1.302 |
| Pioglitazone/Glimepiride | Glycosylated Hemoglobin (HbA1c) | Month 3 (n=1016) | 7.25 percentage of glycosylated haemoglobin | Standard Deviation 1.102 |
| Pioglitazone/Glimepiride | Glycosylated Hemoglobin (HbA1c) | Month 6 (n=893) | 7.14 percentage of glycosylated haemoglobin | Standard Deviation 1.059 |
| Pioglitazone/Glimepiride | Glycosylated Hemoglobin (HbA1c) | Month 9 (n=831) | 7.08 percentage of glycosylated haemoglobin | Standard Deviation 0.995 |
| Pioglitazone/Glimepiride | Glycosylated Hemoglobin (HbA1c) | Month 12 (n=462) | 7.12 percentage of glycosylated haemoglobin | Standard Deviation 1.077 |
| Pioglitazone/Glimepiride | Glycosylated Hemoglobin (HbA1c) | Final Assessment (n=1054) | 7.13 percentage of glycosylated haemoglobin | Standard Deviation 1.1 |