Diabetes Mellitus, Dyslipidemias
Conditions
Keywords
Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Hyperlipidemias, Drug Therapy
Brief summary
The purpose of this study is to compare pioglitazone and metformin combination therapy, twice daily (BID), to glimepiride and metformin combination therapy for treating diabetic subjects with dyslipidemia.
Detailed description
Insulin resistance is a major endocrinopathy preceding the development of hyperglycemia, diabetic dyslipidemia and cardiovascular disease in type 2 diabetes. The most common pattern of dyslipidemia in patients with type 2 diabetes are elevated triglyceride levels, decreased hih-density lipoprotein cholesterol and a predominance of small dense low-density lipoprotein particles. Each of these dyslipidemia features is associated with an increased risk of cardiovascular events. Pioglitazone and Metformin are established drugs which can be used for the treatment of type 2 diabetes. This study will investigate the effects of treatment with fixed Pioglitazone/Metformin combination therapy of Metformin and Glimepiride in Metformin-pretreated type 2 diabetic patients with dyslipidemia. Total participation time in this study is anticipated to be approximately 24 weeks.
Interventions
Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
DRUGGlimepiride and Metformin
Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes according to the American Diabetes Association Criteria. * Treatment with individual maximal tolerated dose of metformin (850 - 2000 mg) as monotherapy within the last 12 weeks. * Glycosylated Hemoglobin greater than or equal to 6.5% and less than or equal to 9%. * Dyslipidemia defined as high-density lipoprotein cholesterol less than or equal to 1.03 mmol/l (40 mg/dL) and/or triglycerides greater than or equal to 1.7 mmol/l (150 mg/dL). * Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
Exclusion criteria
* Type 1 diabetes mellitus. * Insulin-dependent type 2 diabetes mellitus. * Treatment or history of treatment with any insulin formulation other than emergency for more than 2 weeks. * Treatment with other oral antidiabetic drugs in addition to metformin within the last 12 weeks. * Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures. * Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including: * Heparin (and heparin-like drugs) * coumarin * phenprocoumon * hirudin * Protein C * Fondaparinux * antithrombin III * Peroxisome Proliferation Activating Receptor (gamma) agonists * Treatment within the last 12 weeks with: * fibrates * gemfibrozil * niacin * months * Rifampicin * Changes in dosage of any statin treatment to lower low-density lipoprotein within 2 weeks before study entry and during study participation interval. * Changes in dosage of any anticoagulant treatment with acetyl salicylic acid and/or clopidogrel within 2 weeks before study entry and during study participation interval. * Start of statin and/or anticoagulant treatment during study participation interval. * History of severe or multiple allergies and/ or acute severe infections. * Have had more than one unexplained episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit. * Progressive fatal disease. * Any elective surgery during study participation. * History of drug or alcohol abuse within the last 5 years. * A history of significant cardiovascular (New York Heart Association stage I - IV), respiratory, gastrointestinal, hepatic (alanine aminotransferase and/or aspartate aminotransferase greater than 2.5 times the upper limit of the normal reference range), renal (serum creatinine greater than 1.2 mg/dL in women and greater than 1.5 mg/dL in men, glomerular filtration rate less than 60 ml/min as estimated by the Cockroft-Gault formula), neurological, psychiatric and/or hematological disease as judged by the investigator, history of macular edema. * Blood donation within the last 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Increase From Baseline in High-Density Lipoprotein Cholesterol. | Baseline and Week 24. | The increase in High-Density Lipoprotein (HDL) Cholesterol collected at week 24 or final visit and HDL-Cholesterol collected at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in High-Density Lipoprotein Cholesterol. | Baseline and Week 24. | The change between HDL-Cholesterol collected at week 24 or final visit and HDL-Cholesterol collected at baseline. |
| Change From Baseline in High-Density Lipoprotein/Low-Density Lipoprotein Ratio. | Baseline and Week 24. | The change between High-Density Lipoprotein/Low-Density Lipoprotein Ratio collected at week 24 or final visit and High-Density Lipoprotein/Low-Density Lipoprotein Ratio collected at baseline. |
| Change From Baseline in Triglycerides. | Baseline and Week 24. | The change between the value of Triglycerides collected at week 24 or final visit and Triglycerides collected at baseline. |
| Change From Baseline in Low-Density Lipoprotein Subfractions. | Baseline and Week 24. | The change between the value of Low-Density Lipoprotein Subfractions collected at week 24 or final visit and Low-Density Lipoprotein Subfractions collected at baseline. |
| Change From Baseline in Low-Density Lipoprotein Cholesterol. | Baseline and Week 24. | The change between Low-Density Lipoprotein Cholesterol collected at week 24 or final visit and Low-Density Lipoprotein Cholesterol collected at baseline. |
| Change From Baseline in Glycosylated Hemoglobin. | Baseline and Week 24. | The change between the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 24 or final visit and Glycosylated Hemoglobin collected at baseline. |
| Change From Baseline in Fasting Intact Proinsulin. | Baseline and Week 24. | The change between Fasting Intact Proinsulin collected at week 24 or final visit and Fasting Intact Proinsulin collected at baseline. |
| Change From Baseline in Fasting Glucose. | Baseline and Week 24. | The change between Fasting Glucose collected at week 24 or final visit and Fasting Glucose collected at baseline. |
| Change From Baseline in Adiponectin. | Baseline and Week 24. | The change between Adiponectin collected at week 24 or final visit and Adiponectin collected at baseline. |
| Change From Baseline in High Sensitivity C-reactive Protein (Original). | Baseline and Week 24. | The change between the value of High Sensitivity C-reactive Protein collected at week 24 or final visit and High Sensitivity C-reactive Protein collected at baseline. |
| Change From Baseline in High Sensitivity C-reactive Protein (≤ 10 mg/L). | Baseline and Week 24. | The change between the value of High Sensitivity C-reactive Protein less than or equal to 10 mg/L collected at week 24 or final visit and High Sensitivity C-reactive Protein less than or equal to 10 mg/L collected at baseline. |
| Change From Baseline in Systolic Blood Pressure. | Baseline and Week 24. | The change between Systolic Blood Pressure measured at week 24 or final visit and Systolic Blood Pressure measured at baseline. |
| Change From Baseline in Diastolic Blood Pressure. | Baseline and Week 24. | The change between Diastolic Blood Pressure measured at week 24 or final visit and Diastolic Blood Pressure measured at baseline. |
| Intake of Study Medication Greater Than 80% and Less Than 120%. | Baseline and Week 24. | The change between the Intake of study medication greater than 80% at week 24 or final visit and Baseline and the Intake of study medication greater than 80% at baseline. |
| Change From Baseline in Nitrotyrosine. | Baseline and Week 24. | The change between the value of Nitrotyrosine collected at week 24 or final visit and Nitrotyrosine collected at baseline. |
| Change From Baseline in Erythrocyte Deformability (12.00). | Baseline and Week 24. | The change between the 12.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline. |
| Change From Baseline in Matrix Metallo Proteinase-9. | Baseline and Week 24. | The change between the value of Baseline in Matrix Metallo Proteinase-9 collected at week 24 or final visit and Baseline in Matrix Metallo Proteinase-9 collected at baseline. |
| Change From Baseline in Soluble Intracellular Adhesion Molecule. | Baseline and Week 24. | The change between the value of Baseline in Soluble Intracellular Adhesion molecule at week 24 or final visit and Baseline in Soluble Intracellular Adhesion molecule collected at baseline. |
| Change From Baseline in Soluble Vascular Cell Adhesion Molecule. | Baseline and Week 24. | The change between the value of Soluble Vascular Cell Adhesion Molecule collected at week 24 or final visit and Soluble Vascular Cell Adhesion Molecule collected at baseline. |
| Change From Baseline in Thromboxane B2. | Baseline and Week 24. | The change between the value of Thromboxane B2 collected at week 24 or final visit and Thromboxane B2 collected at baseline. |
| Change From Baseline in Platelet Function. | Baseline and Week 24. | The change between the value of Platelet Function by PFA 100 collected at week 24 or final visit and Platelet Function by PFA 100 collected at baseline. |
| Change From Baseline in E-Selectin. | Baseline and Week 24. | The change between the value of E-Selectin collected at week 24 or final visit and E-Selectin collected at baseline. |
| Change From Baseline in Von-Willebrand Factor. | Baseline and Week 24. | The change between the value of Von-Willebrand Factor collected at week 24 or final visit and Von-Willebrand Factor collected at baseline. |
| Change From Baseline in Erythrocyte Deformability (0.30%). | Baseline and Week 24. | The change between the 0.30 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline. |
| Change From Baseline in Erythrocyte Deformability (0.60%) | Baseline and Week 24. | The change between the 0.60 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline. |
| Change From Baseline in Erythrocyte Deformability (1.20). | Baseline and Week 24. | The change between the 1.20 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline. |
| Change From Baseline in Erythrocyte Deformability (3.00). | Baseline and Week 24. | The change between the 3.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline. |
| Change From Baseline in Erythrocyte Deformability (6.00). | Baseline and Week 24. | The change between the 6.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline. |
| Change From Baseline in Erythrocyte Deformability (30.00). | Baseline and Week 24. | The change between the 30.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline. |
| Change From Baseline in Erythrocyte Deformability (60.00). | Baseline and Week 24. | The change between the 60.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline. |
| Change From Baseline in Soluble CD40 Ligand. | Baseline and Week 24. | The change between the value of Soluble CD40 Ligand collected at week 24 or final visit and Soluble CD40 Ligand collected at baseline. |
Countries
Germany
Participant flow
Recruitment details
Subjects were enrolled at 61 investigative sites in Germany from 03 April 2007 to 13 May 2009.
Pre-assignment details
Subjects with type 2 diabetes with diabetic dyslipidemia, inadequately controlled by Metformin monotherapy were enrolled in one of two, twice-daily (BID) combination therapy treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks. | 153 |
| Glimepiride 2 mg and Metformin 850 mg BID Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks. | 149 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 5 |
| Overall Study | Fasting Glucose > 240 mg/dL | 2 | 1 |
| Overall Study | Lack of Compliance | 1 | 4 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 8 | 6 |
| Overall Study | > Three Moderate Hypoglycemic Episodes | 0 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 7 |
| Overall Study | Worsening of Glycosolated Hemoglobin | 2 | 2 |
Baseline characteristics
| Characteristic | Pioglitazone 15 mg and Metformin 850 mg BID | Glimepiride 2 mg and Metformin 850 mg BID | Total |
|---|---|---|---|
| Age Continuous | 58.7 years STANDARD_DEVIATION 10 | 58.5 years STANDARD_DEVIATION 9.6 | 58.6 years STANDARD_DEVIATION 9.8 |
| Region of Enrollment Germany | 153 participants | 149 participants | 302 participants |
| Sex: Female, Male Female | 54 Participants | 55 Participants | 109 Participants |
| Sex: Female, Male Male | 99 Participants | 94 Participants | 193 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 61 / 153 | 61 / 149 |
| serious Total, serious adverse events | 17 / 153 | 8 / 149 |
Outcome results
Primary
The Mean Increase From Baseline in High-Density Lipoprotein Cholesterol.
The increase in High-Density Lipoprotein (HDL) Cholesterol collected at week 24 or final visit and HDL-Cholesterol collected at baseline.
Time frame: Baseline and Week 24.
Population: Analysis was performed on participants with at least one valid baseline and post-baseline measurement. This condition was not fulfilled in 17 participants who were excluded from the all-participants-randomized set, leading to a full-analysis-set of 288 (146 vs. 142). Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | The Mean Increase From Baseline in High-Density Lipoprotein Cholesterol. | 3.2 mg/dL | Standard Error 9.7 |
| Glimepiride 2 mg and Metformin 850 mg BID | The Mean Increase From Baseline in High-Density Lipoprotein Cholesterol. | -0.3 mg/dL | Standard Error 11 |
Comparison: Null hypothesis (H0) = mean increase of HDL after 24 weeks of treatment of Pio/Met group ≤ the mean increase in the Gli/Met group. Alternate hypothesis (H1) = mean increase of HDL after 24 weeks of treatment of Pio/Met group \> the mean increase in the Gli/Met group. The relevant clinical effect size to detect with adequate power was 0.35. With this assumption, a one sided t-test with a type I error rate had 80% power to reject the H0 for the H1 when the sample size was 130 patients per group.p-value: 0.001895% CI: [1.2264, 5.3076]ANCOVA
Secondary
Change From Baseline in Adiponectin.
The change between Adiponectin collected at week 24 or final visit and Adiponectin collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Adiponectin. | 6.79 μg/mL | Standard Error 6.38 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Adiponectin. | 0.72 μg/mL | Standard Error 2.73 |
p-value: <0.000195% CI: [5.0994, 7.5329]ANCOVA
Secondary
Change From Baseline in Diastolic Blood Pressure.
The change between Diastolic Blood Pressure measured at week 24 or final visit and Diastolic Blood Pressure measured at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Diastolic Blood Pressure. | -1.3 mmHg | Standard Deviation 8.7 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Diastolic Blood Pressure. | -0.1 mmHg | Standard Deviation 8.8 |
p-value: 0.327995% CI: [-2.6571, 0.8906]ANCOVA
Secondary
Change From Baseline in Erythrocyte Deformability (0.30%).
The change between the 0.30 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (0.30%). | 1.3 percent | Standard Deviation 2.1 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (0.30%). | -0.4 percent | Standard Deviation 1.7 |
p-value: 0.176195% CI: [-0.4843, 2.4712]ANCOVA
Secondary
Change From Baseline in Erythrocyte Deformability (0.60%)
The change between the 0.60 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (0.60%) | 2.4 percent | Standard Deviation 1.3 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (0.60%) | -0.5 percent | Standard Deviation 1.1 |
p-value: 0.000295% CI: [1.3832, 3.6695]ANCOVA
Secondary
Change From Baseline in Erythrocyte Deformability (1.20).
The change between the 1.20 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (1.20). | 3.2 percent | Standard Deviation 2.2 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (1.20). | -1.1 percent | Standard Deviation 2.5 |
p-value: 0.005595% CI: [1.0675, 5.4016]ANCOVA
Secondary
Change From Baseline in Erythrocyte Deformability (12.00).
The change between the 12.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (12.00). | 2.7 percent | Standard Deviation 2.8 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (12.00). | -1.3 percent | Standard Deviation 2.9 |
p-value: 0.101395% CI: [-0.466, 4.8097]ANCOVA
Secondary
Change From Baseline in Erythrocyte Deformability (3.00).
The change between the 3.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (3.00). | 3.3 percent | Standard Deviation 2.8 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (3.00). | -.15 percent | Standard Deviation 3.1 |
p-value: 0.026495% CI: [0.3863, 5.5562]ANCOVA
Secondary
Change From Baseline in Erythrocyte Deformability (30.00).
The change between the 30.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (30.00). | 2.5 percent | Standard Deviation 2.6 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (30.00). | -1.3 percent | Standard Deviation 3.5 |
p-value: 0.136395% CI: [-0.7338, 5.0031]ANCOVA
Secondary
Change From Baseline in Erythrocyte Deformability (6.00).
The change between the 6.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (6.00). | 3.1 percent | Standard Deviation 2.9 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (6.00). | -1.4 percent | Standard Deviation 2.9 |
p-value: 0.050995% CI: [-0.0114, 5.0901]ANCOVA
Secondary
Change From Baseline in Erythrocyte Deformability (60.00).
The change between the 60.00 percent value of Erythrocyte (Red Blood Cell) Deformability collected at week 24 or final visit and Erythrocyte Deformability collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (60.00). | 2.7 percent | Standard Deviation 2.6 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Erythrocyte Deformability (60.00). | -1.3 percent | Standard Deviation 3.9 |
p-value: 0.116595% CI: [-0.6561, 5.4922]ANCOVA
Secondary
Change From Baseline in E-Selectin.
The change between the value of E-Selectin collected at week 24 or final visit and E-Selectin collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in E-Selectin. | -3.7 ng/mL | Standard Error 4.8 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in E-Selectin. | -0.5 ng/mL | Standard Error 3.4 |
p-value: 0.013895% CI: [-4.3207, -0.5202]ANCOVA
Secondary
Change From Baseline in Fasting Glucose.
The change between Fasting Glucose collected at week 24 or final visit and Fasting Glucose collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Fasting Glucose. | -21.6 mg/dL | Standard Error 38.6 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Fasting Glucose. | -21.1 mg/dL | Standard Error 40.4 |
p-value: 0.779995% CI: [-6.4665, 8.6079]ANCOVA
Secondary
Change From Baseline in Fasting Intact Proinsulin.
The change between Fasting Intact Proinsulin collected at week 24 or final visit and Fasting Intact Proinsulin collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Fasting Intact Proinsulin. | -5.18 pmol/L | Standard Error 11.89 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Fasting Intact Proinsulin. | -0.11 pmol/L | Standard Error 9.84 |
p-value: <0.000195% CI: [-6.4222, -2.5855]ANCOVA
Secondary
Change From Baseline in Glycosylated Hemoglobin.
The change between the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 24 or final visit and Glycosylated Hemoglobin collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Glycosylated Hemoglobin. | -0.83 mg/dL | Standard Error 0.87 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Glycosylated Hemoglobin. | -0.95 mg/dL | Standard Error 0.85 |
p-value: 0.080795% CI: [-0.0193, 0.3341]ANCOVA
Secondary
Change From Baseline in High-Density Lipoprotein Cholesterol.
The change between HDL-Cholesterol collected at week 24 or final visit and HDL-Cholesterol collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in High-Density Lipoprotein Cholesterol. | 3.3 mg/dL | Standard Error 9.6 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in High-Density Lipoprotein Cholesterol. | -0.4 mg/dL | Standard Error 11.1 |
p-value: 0.001895% CI: [1.2264, 5.3076]ANCOVA
Secondary
Change From Baseline in High-Density Lipoprotein/Low-Density Lipoprotein Ratio.
The change between High-Density Lipoprotein/Low-Density Lipoprotein Ratio collected at week 24 or final visit and High-Density Lipoprotein/Low-Density Lipoprotein Ratio collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in High-Density Lipoprotein/Low-Density Lipoprotein Ratio. | 0.1 mg/dL | Standard Error 0.8 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in High-Density Lipoprotein/Low-Density Lipoprotein Ratio. | 0.3 mg/dL | Standard Error 0.7 |
p-value: 0.116795% CI: [-0.2951, 0.0329]ANCOVA
Secondary
Change From Baseline in High Sensitivity C-reactive Protein (≤ 10 mg/L).
The change between the value of High Sensitivity C-reactive Protein less than or equal to 10 mg/L collected at week 24 or final visit and High Sensitivity C-reactive Protein less than or equal to 10 mg/L collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in High Sensitivity C-reactive Protein (≤ 10 mg/L). | -0.87 mg/L | Standard Deviation 1.88 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in High Sensitivity C-reactive Protein (≤ 10 mg/L). | 0.00 mg/L | Standard Deviation 1.83 |
p-value: <0.000195% CI: [-1.3067, -0.4627]ANCOVA
Secondary
Change From Baseline in High Sensitivity C-reactive Protein (Original).
The change between the value of High Sensitivity C-reactive Protein collected at week 24 or final visit and High Sensitivity C-reactive Protein collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in High Sensitivity C-reactive Protein (Original). | -0.21 mg/L | Standard Error 8.98 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in High Sensitivity C-reactive Protein (Original). | -0.04 mg/L | Standard Error 9.53 |
p-value: 0.413195% CI: [-2.8312, 1.1665]ANCOVA
Secondary
Change From Baseline in Low-Density Lipoprotein Cholesterol.
The change between Low-Density Lipoprotein Cholesterol collected at week 24 or final visit and Low-Density Lipoprotein Cholesterol collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Low-Density Lipoprotein Cholesterol. | 9.7 mg/dL | Standard Error 34.7 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Low-Density Lipoprotein Cholesterol. | 11.2 mg/dL | Standard Error 25.3 |
p-value: 0.946495% CI: [-7.1253, 6.6543]ANCOVA
Secondary
Change From Baseline in Low-Density Lipoprotein Subfractions.
The change between the value of Low-Density Lipoprotein Subfractions collected at week 24 or final visit and Low-Density Lipoprotein Subfractions collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Low-Density Lipoprotein Subfractions. | 6.2 mg/dL | Standard Error 17.5 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Low-Density Lipoprotein Subfractions. | 6.1 mg/dL | Standard Error 26.4 |
p-value: 0.748695% CI: [-17.0109, 23.2693]ANCOVA
Secondary
Change From Baseline in Matrix Metallo Proteinase-9.
The change between the value of Baseline in Matrix Metallo Proteinase-9 collected at week 24 or final visit and Baseline in Matrix Metallo Proteinase-9 collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Matrix Metallo Proteinase-9. | 31.4 ng/mL | Standard Error 228.3 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Matrix Metallo Proteinase-9. | 51.6 ng/mL | Standard Error 216.4 |
p-value: 0.718695% CI: [-163.3229, 113.6052]ANCOVA
Secondary
Change From Baseline in Nitrotyrosine.
The change between the value of Nitrotyrosine collected at week 24 or final visit and Nitrotyrosine collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Nitrotyrosine. | -2.7 nmol/L | Standard Error 93.2 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Nitrotyrosine. | 32.5 nmol/L | Standard Error 147.2 |
p-value: 0.351795% CI: [-94.1999, 34.2967]ANCOVA
Secondary
Change From Baseline in Platelet Function.
The change between the value of Platelet Function by PFA 100 collected at week 24 or final visit and Platelet Function by PFA 100 collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from the Mainz, Germany study site. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Platelet Function. | -30.3 sec | Standard Error 44.3 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Platelet Function. | -1.0 sec | Standard Error 102.5 |
p-value: 0.58595% CI: [-95.6468, 151.8057]ANCOVA
Secondary
Change From Baseline in Soluble CD40 Ligand.
The change between the value of Soluble CD40 Ligand collected at week 24 or final visit and Soluble CD40 Ligand collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Soluble CD40 Ligand. | -40.7 pg/mL | Standard Error 248.6 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Soluble CD40 Ligand. | 102.4 pg/mL | Standard Error 379.8 |
p-value: 0.197995% CI: [-386.2256, 83.3302]ANCOVA
Secondary
Change From Baseline in Soluble Intracellular Adhesion Molecule.
The change between the value of Baseline in Soluble Intracellular Adhesion molecule at week 24 or final visit and Baseline in Soluble Intracellular Adhesion molecule collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Soluble Intracellular Adhesion Molecule. | -13.0 ng/mL | Standard Error 46.9 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Soluble Intracellular Adhesion Molecule. | -3.2 ng/mL | Standard Error 50 |
p-value: 0.505895% CI: [-39.9915, 20.0459]ANCOVA
Secondary
Change From Baseline in Soluble Vascular Cell Adhesion Molecule.
The change between the value of Soluble Vascular Cell Adhesion Molecule collected at week 24 or final visit and Soluble Vascular Cell Adhesion Molecule collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Soluble Vascular Cell Adhesion Molecule. | 11.6 ng/mL | Standard Error 160.6 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Soluble Vascular Cell Adhesion Molecule. | 3.3 ng/mL | Standard Error 115.4 |
p-value: 0.52395% CI: [-60.7193, 117.5169]ANCOVA
Secondary
Change From Baseline in Systolic Blood Pressure.
The change between Systolic Blood Pressure measured at week 24 or final visit and Systolic Blood Pressure measured at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Systolic Blood Pressure. | -2.5 mmHg | Standard Error 14.8 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Systolic Blood Pressure. | 0.5 mmHg | Standard Error 13.8 |
p-value: 0.092995% CI: [-5.3979, 0.4172]ANCOVA
Secondary
Change From Baseline in Thromboxane B2.
The change between the value of Thromboxane B2 collected at week 24 or final visit and Thromboxane B2 collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Thromboxane B2. | -216.4 pg/mL | Standard Error 842.9 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Thromboxane B2. | 527.8 pg/mL | Standard Error 1190.4 |
p-value: 0.220395% CI: [-964.3923, 229.8646]ANCOVA
Secondary
Change From Baseline in Triglycerides.
The change between the value of Triglycerides collected at week 24 or final visit and Triglycerides collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Triglycerides. | -40.9 mg/dL | Standard Error 113.8 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Triglycerides. | -16.7 mg/dL | Standard Error 121.6 |
p-value: 0.101295% CI: [-39.4331, 3.5373]ANCOVA
Secondary
Change From Baseline in Von-Willebrand Factor.
The change between the value of Von-Willebrand Factor collected at week 24 or final visit and Von-Willebrand Factor collected at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. The number of participants for analysis was derived from a subgroup of participants from Schwerin, Berlin, Hanover and Münster study sites. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Change From Baseline in Von-Willebrand Factor. | -19.5 percent | Standard Error 32 |
| Glimepiride 2 mg and Metformin 850 mg BID | Change From Baseline in Von-Willebrand Factor. | 1.4 percent | Standard Error 33.2 |
p-value: 0.081795% CI: [-30.1139, 1.8578]ANCOVA
Secondary
Intake of Study Medication Greater Than 80% and Less Than 120%.
The change between the Intake of study medication greater than 80% at week 24 or final visit and Baseline and the Intake of study medication greater than 80% at baseline.
Time frame: Baseline and Week 24.
Population: Analyses was performed for the full analysis and per-protocol set. This condition was not fulfilled in some participants who were excluded. Last observation carried forward was used (LOCF) in case of premature termination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone 15 mg and Metformin 850 mg BID | Intake of Study Medication Greater Than 80% and Less Than 120%. | 136 participants |
| Glimepiride 2 mg and Metformin 850 mg BID | Intake of Study Medication Greater Than 80% and Less Than 120%. | 137 participants |
Comparison: The number and percentage of participants with a calculated compliance \>80% and \<120% are presented for both treatment groups. In addition, the p-values of Fisher's exact test, the two-sided 95% confidence intervals for the percentage of patients per treatment group and for the difference between the treatment groups are provided.p-value: 0.289595% CI: [-14.83, 8.39]Fisher Exact