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Efficacy of Pioglitazone/Metformin Combination Therapy in Subjects With Type 2 Diabetes Mellitus and Dyslipidemia.

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ClinicalTrials.gov Identifier: NCT00770653
Recruitment Status : Completed
First Posted : October 10, 2008
Results First Posted : October 6, 2010
Last Update Posted : October 6, 2010
Sponsor:
Information provided by:
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Diabetes Mellitus
Dyslipidemias
Interventions Drug: Pioglitazone and Metformin
Drug: Glimepiride and Metformin
Enrollment 305
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.
Arm/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 155 150
Completed 123 121
Not Completed 32 29
Reason Not Completed
Adverse Event             13             5
Protocol Violation             8             6
Withdrawal by Subject             4             7
Lack of Compliance             1             4
Worsening of Glycosolated Hemoglobin             2             2
Fasting Glucose > 240 mg/dL             2             1
> Three Moderate Hypoglycemic Episodes             0             2
Lost to Follow-up             1             2
Physician Decision             1             0
Arm/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 153 149 302
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 153 participants 149 participants 302 participants
58.7  (10.0) 58.5  (9.6) 58.6  (9.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 153 participants 149 participants 302 participants
Female
54
  35.3%
55
  36.9%
109
  36.1%
Male
99
  64.7%
94
  63.1%
193
  63.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Germany Number Analyzed 153 participants 149 participants 302 participants
153 149 302
1.Primary Outcome
Title The Mean Increase From Baseline in High-Density Lipoprotein Cholesterol.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 146 142
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
3.2  (9.7) -0.3  (11.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.2670
Confidence Interval (2-Sided) 95%
1.2264 to 5.3076
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in High-Density Lipoprotein Cholesterol.
Hide Description The change between HDL-Cholesterol collected at week 24 or final visit and HDL-Cholesterol collected at baseline.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 143 137
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
3.3  (9.6) -0.4  (11.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.2670
Confidence Interval (2-Sided) 95%
1.2264 to 5.3076
Estimation Comments Deviation from the normal distribution assumption was detected for original and rank-transformed data for all time-points due to p-value of Shapiro-Wilk test, indicating the normal distribution assumption might be distrusted for HDL-cholesterol data.
3.Secondary Outcome
Title Change From Baseline in High-Density Lipoprotein/Low-Density Lipoprotein Ratio.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 141 132
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
0.1  (0.8) 0.3  (0.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1167
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1311
Confidence Interval (2-Sided) 95%
-0.2951 to 0.0329
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Triglycerides.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 146 142
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-40.9  (113.8) -16.7  (121.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1012
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -17.9479
Confidence Interval (2-Sided) 95%
-39.4331 to 3.5373
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Low-Density Lipoprotein Subfractions.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 11
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
6.2  (17.5) 6.1  (26.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7486
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.1292
Confidence Interval (2-Sided) 95%
-17.0109 to 23.2693
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Low-Density Lipoprotein Cholesterol.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 143 132
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
9.7  (34.7) 11.2  (25.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9464
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2355
Confidence Interval (2-Sided) 95%
-7.1253 to 6.6543
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 139 136
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-0.83  (0.87) -0.95  (0.85)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0807
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1574
Confidence Interval (2-Sided) 95%
-0.0193 to 0.3341
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Fasting Intact Proinsulin.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 144 137
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-5.18  (11.89) -0.11  (9.84)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.5039
Confidence Interval (2-Sided) 95%
-6.4222 to -2.5855
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Fasting Glucose.
Hide Description The change between Fasting Glucose collected at week 24 or final visit and Fasting Glucose collected at baseline.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 145 139
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-21.6  (38.6) -21.1  (40.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7799
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.0707
Confidence Interval (2-Sided) 95%
-6.4665 to 8.6079
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Adiponectin.
Hide Description The change between Adiponectin collected at week 24 or final visit and Adiponectin collected at baseline.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 146 139
Least Squares Mean (Standard Error)
Unit of Measure: μg/mL
6.79  (6.38) 0.72  (2.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.3161
Confidence Interval (2-Sided) 95%
5.0994 to 7.5329
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in High Sensitivity C-reactive Protein (Original).
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 141 135
Least Squares Mean (Standard Error)
Unit of Measure: mg/L
-0.21  (8.98) -0.04  (9.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4131
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.8323
Confidence Interval (2-Sided) 95%
-2.8312 to 1.1665
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in High Sensitivity C-reactive Protein (≤ 10 mg/L).
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 123 113
Mean (Standard Deviation)
Unit of Measure: mg/L
-0.87  (1.88) 0.00  (1.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.8847
Confidence Interval (2-Sided) 95%
-1.3067 to -0.4627
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in Systolic Blood Pressure.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 146 142
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-2.5  (14.8) 0.5  (13.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0929
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.4903
Confidence Interval (2-Sided) 95%
-5.3979 to 0.4172
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in Diastolic Blood Pressure.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 146 142
Least Squares Mean (Standard Deviation)
Unit of Measure: mmHg
-1.3  (8.7) -0.1  (8.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3279
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.8832
Confidence Interval (2-Sided) 95%
-2.6571 to 0.8906
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Intake of Study Medication Greater Than 80% and Less Than 120%.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 146 142
Measure Type: Number
Unit of Measure: participants
136 137
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2895
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Fisher Exact
Estimated Value -3.33
Confidence Interval (2-Sided) 95%
-14.83 to 8.39
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Change From Baseline in Nitrotyrosine.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 23 20
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
-2.7  (93.2) 32.5  (147.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3517
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -29.9516
Confidence Interval (2-Sided) 95%
-94.1999 to 34.2967
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Change From Baseline in Soluble CD40 Ligand.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 16 18
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
-40.7  (248.6) 102.4  (379.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1979
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -151.4477
Confidence Interval (2-Sided) 95%
-386.2256 to 83.3302
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Change From Baseline in Matrix Metallo Proteinase-9.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 23 20
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
31.4  (228.3) 51.6  (216.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7186
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -24.8589
Confidence Interval (2-Sided) 95%
-163.3229 to 113.6052
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline in Soluble Intracellular Adhesion Molecule.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 23 20
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
-13.0  (46.9) -3.2  (50.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5058
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -9.9728
Confidence Interval (2-Sided) 95%
-39.9915 to 20.0459
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Change From Baseline in Soluble Vascular Cell Adhesion Molecule.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 22 20
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
11.6  (160.6) 3.3  (115.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5230
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 28.3988
Confidence Interval (2-Sided) 95%
-60.7193 to 117.5169
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change From Baseline in Thromboxane B2.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 19 20
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
-216.4  (842.9) 527.8  (1190.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2203
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -367.2639
Confidence Interval (2-Sided) 95%
-964.3923 to 229.8646
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Change From Baseline in Platelet Function.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 3 5
Least Squares Mean (Standard Error)
Unit of Measure: sec
-30.3  (44.3) -1.0  (102.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5850
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 28.0794
Confidence Interval (2-Sided) 95%
-95.6468 to 151.8057
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Change From Baseline in E-Selectin.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 23 20
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
-3.7  (4.8) -0.5  (3.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0138
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.4205
Confidence Interval (2-Sided) 95%
-4.3207 to -0.5202
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Change From Baseline in Von-Willebrand Factor.
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 24 20
Least Squares Mean (Standard Error)
Unit of Measure: percent
-19.5  (32.0) 1.4  (33.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0817
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0009
Confidence Interval (2-Sided) 95%
-30.1139 to 1.8578
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Change From Baseline in Erythrocyte Deformability (0.30%).
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 12
Mean (Standard Deviation)
Unit of Measure: percent
1.3  (2.1) -0.4  (1.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1761
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.9935
Confidence Interval (2-Sided) 95%
-0.4843 to 2.4712
Estimation Comments [Not Specified]
26.Secondary Outcome
Title Change From Baseline in Erythrocyte Deformability (0.60%)
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 12
Mean (Standard Deviation)
Unit of Measure: percent
2.4  (1.3) -0.5  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.5263
Confidence Interval (2-Sided) 95%
1.3832 to 3.6695
Estimation Comments [Not Specified]
27.Secondary Outcome
Title Change From Baseline in Erythrocyte Deformability (1.20).
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 12
Mean (Standard Deviation)
Unit of Measure: percent
3.2  (2.2) -1.1  (2.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0055
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.2345
Confidence Interval (2-Sided) 95%
1.0675 to 5.4016
Estimation Comments [Not Specified]
28.Secondary Outcome
Title Change From Baseline in Erythrocyte Deformability (3.00).
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 12
Mean (Standard Deviation)
Unit of Measure: percent
3.3  (2.8) -.15  (3.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0264
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.9712
Confidence Interval (2-Sided) 95%
0.3863 to 5.5562
Estimation Comments [Not Specified]
29.Secondary Outcome
Title Change From Baseline in Erythrocyte Deformability (6.00).
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 12
Mean (Standard Deviation)
Unit of Measure: percent
3.1  (2.9) -1.4  (2.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0509
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.5394
Confidence Interval (2-Sided) 95%
-0.0114 to 5.0901
Estimation Comments [Not Specified]
30.Secondary Outcome
Title Change From Baseline in Erythrocyte Deformability (12.00).
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 12
Mean (Standard Deviation)
Unit of Measure: percent
2.7  (2.8) -1.3  (2.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1013
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.1718
Confidence Interval (2-Sided) 95%
-0.4660 to 4.8097
Estimation Comments [Not Specified]
31.Secondary Outcome
Title Change From Baseline in Erythrocyte Deformability (30.00).
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 12
Mean (Standard Deviation)
Unit of Measure: percent
2.5  (2.6) -1.3  (3.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1363
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.1346
Confidence Interval (2-Sided) 95%
-0.7338 to 5.0031
Estimation Comments [Not Specified]
32.Secondary Outcome
Title Change From Baseline in Erythrocyte Deformability (60.00).
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 12
Mean (Standard Deviation)
Unit of Measure: percent
2.7  (2.6) -1.3  (3.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg and Metformin 850 mg BID, Glimepiride 2 mg and Metformin 850 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1165
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.4181
Confidence Interval (2-Sided) 95%
-0.6561 to 5.4922
Estimation Comments [Not Specified]
Time Frame 1 year and 11 months. Treatment-emergent adverse events are defined as those occurring after signature of consent form and no more than 14 days after the end of the study.
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Irrespective of the relation to study treatment, any event spontaneously reported by the participant or observed by the investigator was recorded.
 
Arm/Group Title Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   17/153 (11.11%)   8/149 (5.37%) 
Blood and lymphatic system disorders     
Leukocytosis  1  1/153 (0.65%)  0/149 (0.00%) 
Thrombocytopenia  1  1/153 (0.65%)  0/149 (0.00%) 
Cardiac disorders     
Cardiac failure  1  2/153 (1.31%)  0/149 (0.00%) 
Cardiomegaly  1  1/153 (0.65%)  0/149 (0.00%) 
Coronary artery disease  1  0/153 (0.00%)  1/149 (0.67%) 
Tachycardia  1  1/153 (0.65%)  0/149 (0.00%) 
Gastrointestinal disorders     
Abdominal adhesions  1  0/153 (0.00%)  1/149 (0.67%) 
Subileus  1  0/153 (0.00%)  1/149 (0.67%) 
General disorders     
Chest pain  1  1/153 (0.65%)  0/149 (0.00%) 
Hepatobiliary disorders     
Hepatic failure  1  1/153 (0.65%)  0/149 (0.00%) 
Investigations     
Tumour marker increased  1  1/153 (0.65%)  0/149 (0.00%) 
Metabolism and nutrition disorders     
Diabetes mellitus  1  1/153 (0.65%)  0/149 (0.00%) 
Hyperkalaemia  1  1/153 (0.65%)  0/149 (0.00%) 
Hyponatraemia  1  1/153 (0.65%)  0/149 (0.00%) 
Lactic acidosis  1  1/153 (0.65%)  0/149 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign breast neoplasm  1  1/153 (0.65%)  0/149 (0.00%) 
Prostate cancer  1  0/153 (0.00%)  1/149 (0.67%) 
Nervous system disorders     
Carotid artery stenosis  1  0/153 (0.00%)  1/149 (0.67%) 
Psychiatric disorders     
Depression  1  1/153 (0.65%)  0/149 (0.00%) 
Mental disorder due to a general medical condition  1  1/153 (0.65%)  0/149 (0.00%) 
Renal and urinary disorders     
Renal failure acute  1  1/153 (0.65%)  0/149 (0.00%) 
Urinary retention  1  0/153 (0.00%)  1/149 (0.67%) 
Vascular disorders     
Hypertensive crisis  1  0/153 (0.00%)  1/149 (0.67%) 
Peripheral arterial occlusive disease  1  0/153 (0.00%)  1/149 (0.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pioglitazone 15 mg and Metformin 850 mg BID Glimepiride 2 mg and Metformin 850 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   61/153 (39.87%)   61/149 (40.94%) 
Gastrointestinal disorders     
Diarrhoea  1  14/153 (9.15%)  14/149 (9.40%) 
General disorders     
Oedema peripheral  1  8/153 (5.23%)  4/149 (2.68%) 
Infections and infestations     
Nasopharyngitis  1  24/153 (15.69%)  33/149 (22.15%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  8/153 (5.23%)  3/149 (2.01%) 
Nervous system disorders     
Headache  1  7/153 (4.58%)  7/149 (4.70%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 14 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda Pharma GmbH, Aachen (Germany)
Phone: +49 800 8253325
Responsible Party: Medical Director, Takeda Pharma GmbH, Aachen (Germany)
ClinicalTrials.gov Identifier: NCT00770653     History of Changes
Other Study ID Numbers: ATS K024
2006-004455-37 ( EudraCT Number )
D-PIO-114 ( Other Identifier: Takeda Pharma GmbH )
U1111-1114-1678 ( Registry Identifier: WHO )
First Submitted: October 9, 2008
First Posted: October 10, 2008
Results First Submitted: September 13, 2010
Results First Posted: October 6, 2010
Last Update Posted: October 6, 2010