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Efficacy and Safety of Pioglitazone and Metformin Combination Therapy in Treating Type 2 Diabetes Mellitus.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00727857
Recruitment Status : Completed
First Posted : August 4, 2008
Results First Posted : March 9, 2010
Last Update Posted : July 29, 2011
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
Condition Diabetes Mellitus
Interventions Drug: Pioglitazone and metformin
Drug: Pioglitazone
Drug: Metformin
Enrollment 600
Recruitment Details Participants were enrolled at 134 investigative sites in the United States (including Puerto Rico), Argentina, Chile, Guatemala, Mexico and Peru from 13 June 2007 to 29 August 2008.
Pre-assignment Details Participants who had not received treatment with antidiabetic medication 12 weeks prior to Screening were enrolled in one of three, twice-daily (BID) treatment groups.
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Period Title: Overall Study
Started 201 189 210
Completed 157 125 142
Not Completed 44 64 68
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID Total
Hide Arm/Group Description Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks. Total of all reporting groups
Overall Number of Baseline Participants 201 189 210 600
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 201 participants 189 participants 210 participants 600 participants
54.7  (12.23) 54.0  (12.08) 53.7  (12.00) 54.1  (12.09)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 189 participants 210 participants 600 participants
Female
111
  55.2%
123
  65.1%
112
  53.3%
346
  57.7%
Male
90
  44.8%
66
  34.9%
98
  46.7%
254
  42.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 201 participants 189 participants 210 participants 600 participants
American Indian or Alaska Native 2 6 6 14
Asian 3 5 5 13
Black or African American 12 13 14 39
Native Hawaiian or Other Pacific Islander 0 0 0 0
White 123 109 124 356
Multiracial 61 56 61 178
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m²
Number Analyzed 201 participants 189 participants 210 participants 600 participants
30.84  (5.74) 31.18  (5.50) 30.83  (5.66) 30.94  (5.63)
1.Primary Outcome
Title Percent 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 final visit or week 24 and Glycosylated Hemoglobin collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant must have baseline and at least one post-baseline value. Last Observation Carried Forward (LOCF) for missing final/week 24 visit
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 188 162 193
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-1.83  (0.122) -0.96  (0.131) -0.99  (0.120)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way Analysis of Covariance (ANCOVA) with treatment as a factor and the baseline value as a covariate. Least Squares (LS) mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.86
Confidence Interval 95%
0.51 to 1.22
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.84
Confidence Interval 95%
0.50 to 1.18
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8919
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.02
Confidence Interval 95%
-0.37 to 0.33
Estimation Comments Mean Difference = Pioglitazone - metformin
2.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose
Hide Description The change between the value of Fasting Plasma Glucose collected at final visit or week 24 and Fasting Plasma Glucose collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant must have baseline and at least one post-baseline value. LOCF for missing final/week 24 visit
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 196 176 202
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-39.9  (3.48) -22.2  (3.67) -24.8  (3.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 17.8
Confidence Interval 95%
7.8 to 27.7
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 15.1
Confidence Interval 95%
5.5 to 24.7
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5981
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.6
Confidence Interval 95%
-12.5 to 7.2
Estimation Comments Mean Difference = Pioglitazone - metformin
3.Secondary Outcome
Title Change From Baseline in Fasting Insulin
Hide Description The change between the Fasting Insulin value collected at final visit or week 24 and Fasting Insulin collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant must have baseline and at least one post-baseline value. LOCF for missing final/week 24 visit
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 178 146 185
Least Squares Mean (Standard Error)
Unit of Measure: μIU/mL
-3.91  (0.736) -3.18  (0.812) -0.98  (0.722)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5074
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.73
Confidence Interval 95%
-1.43 to 2.88
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0047
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.93
Confidence Interval 95%
0.90 to 4.95
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0435
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.20
Confidence Interval 95%
0.06 to 4.33
Estimation Comments Mean Difference = Pioglitazone - metformin
4.Secondary Outcome
Title Change From Baseline in Homeostasis Model Assessment - Insulin Resistance
Hide Description The change between Homeostasis Model Assessment of Insulin Resistance collected at final visit or week 24 and Homeostasis Model Assessment of Insulin Resistance collected at baseline. Homeostasis Model Assessment measures insulin resistance, calculated by insulin times glucose, divided by a constant (22.5).
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant must have baseline and at least one post-baseline value. LOCF for missing final/week 24 visit
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 160 139 172
Least Squares Mean (Standard Error)
Unit of Measure: percent of insulin resistance
-2.704  (0.4274) -2.075  (0.4586) -1.085  (0.4123)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3158
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.629
Confidence Interval 95%
-0.602 to 1.861
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0067
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.619
Confidence Interval 95%
0.452 to 2.785
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1094
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.989
Confidence Interval 95%
-0.223 to 2.201
Estimation Comments Mean Difference = Pioglitazone - metformin
5.Secondary Outcome
Title Median Percent Change From Baseline in High Sensitivity C-reactive Protein
Hide Description Measurement for High Sensitivity C-reactive Protein was collected at final visit or week 24 and at baseline. Percent change from baseline is calculated as: [(Week 24 - baseline levels)/baseline]*100
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 190 168 196
Median (Full Range)
Unit of Measure: percent
-36.7
(-97.7 to 2060.0)
-34.0
(-98.9 to 2314.6)
-26.2
(-99.5 to 1636.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments Nonparametric ANCOVA based on Tukey's normal rank transformation with a term for treatment and the baseline value as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5963
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 4.88
Confidence Interval 95%
-4.71 to 13.97
Estimation Comments The estimate of the median percent change from baseline and 95% confidence intervals were based on the Hodges-Lehmann method and the distribution-free confidence interval.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments Nonparametric ANCOVA based on Tukey's normal rank transformation with a term for treatment and the baseline value as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0265
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 12.81
Confidence Interval 95%
2.88 to 22.24
Estimation Comments The estimate of the median percent change from baseline and 95% confidence intervals were based on the Hodges-Lehmann method and the distribution-free confidence interval.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments Nonparametric ANCOVA based on Tukey's normal rank transformation with a term for treatment and the baseline value as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1053
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 8.33
Confidence Interval 95%
-1.77 to 18.07
Estimation Comments The estimate of the median percent change from baseline and 95% confidence intervals were based on the Hodges-Lehmann method and the distribution-free confidence interval.
6.Secondary Outcome
Title Change From Baseline in Adiponectin
Hide Description The change between Adiponectin collected at final visit or week 24 and Adiponectin collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant must have baseline and at least one post-baseline value. LOCF for missing final/week 24 visit
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 179 148 183
Least Squares Mean (Standard Error)
Unit of Measure: mcg/ml
7.8  (0.55) 9.2  (0.61) -0.3  (0.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0806
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.4
Confidence Interval 95%
-0.2 to 3.1
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.1
Confidence Interval 95%
-9.6 to -6.5
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -9.5
Confidence Interval 95%
-11.1 to -7.9
Estimation Comments Mean Difference = Pioglitazone - metformin
7.Secondary Outcome
Title Change From Baseline in Total Cholesterol
Hide Description The change between Total Cholesterol collected at final visit or week 24 and Total Cholesterol collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant must have baseline and at least one post-baseline value. LOCF for missing final/week 24 visit
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 178 154 182
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
1.06  (1.183) 4.79  (1.271) -2.72  (1.169)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0324
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.73
Confidence Interval 95%
0.31 to 7.14
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0233
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.78
Confidence Interval 95%
-7.05 to -0.52
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.51
Confidence Interval 95%
-10.90 to -4.12
Estimation Comments Mean Difference = Pioglitazone - metformin
8.Secondary Outcome
Title Change From Baseline in Low-Density Lipoprotein Cholesterol
Hide Description The change between Low-Density Lipoprotein Cholesterol collected at final visit or week 24 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
Participant must have baseline and at least one post-baseline value. LOCF for missing final/week 24 visit
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 177 152 180
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
1.19  (2.015) 6.08  (2.175) -1.37  (1.998)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0993
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.90
Confidence Interval 95%
-0.93 to 10.72
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3670
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.56
Confidence Interval 95%
-8.14 to 3.01
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0119
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.46
Confidence Interval 95%
-13.26 to -1.66
Estimation Comments Mean Difference = Pioglitazone - metformin
9.Secondary Outcome
Title Change From Baseline in High-Density Lipoprotein Cholesterol
Hide Description The change between High-Density Lipoprotein Cholesterol collected at final visit or week 24 and High-Density Lipoprotein Cholesterol collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant must have baseline and at least one post-baseline value. LOCF for missing final/week 24 visit
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 177 152 180
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
14.20  (1.440) 9.88  (1.552) 6.09  (1.426)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0423
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.31
Confidence Interval 95%
-8.48 to -0.15
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.10
Confidence Interval 95%
-12.08 to -4.12
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.728
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.79
Confidence Interval 95%
-7.93 to 0.35
Estimation Comments Mean Difference = Pioglitazone - metformin
10.Secondary Outcome
Title Change From Baseline in Triglycerides
Hide Description The change between Triglycerides collected at final visit or week 24 and Triglycerides collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant must have baseline and at least one post-baseline value. LOCF for missing final/week 24 visit
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 180 157 184
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-5.95  (2.901) -5.54  (3.107) -1.78  (2.871)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9231
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.41
Confidence Interval 95%
-7.94 to 8.76
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3082
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.16
Confidence Interval 95%
-3.86 to 12.19
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3753
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.75
Confidence Interval 95%
-4.56 to 12.07
Estimation Comments Mean Difference = Pioglitazone - metformin
11.Secondary Outcome
Title Change From Baseline in Mean Low Density Lipoprotein Particle Concentration
Hide Description The change between Low Density Lipoprotein particle concentration collected at final visit or week 24 and Low Density Lipoprotein particle concentration collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant must have baseline and at least one post-baseline value. LOCF for missing final/week 24 visit
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
-240.6  (23.50) -217.2  (25.40) -176.4  (23.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with a term for treatment and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4999
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 23.4
Confidence Interval 95%
-44.6 to 91.4
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with a term for treatment and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0531
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 64.2
Confidence Interval 95%
-0.9 to 129.3
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with a term for treatment and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2369
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 40.9
Confidence Interval 95%
-26.9 to 108.7
Estimation Comments Mean Difference = Pioglitazone - metformin
12.Secondary Outcome
Title Change From Baseline in Mean Low Density Lipoprotein Particle Size
Hide Description The change between Low Density Lipoprotein collected at final visit or week 24 and Low Density Lipoprotein collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Deviation)
Unit of Measure: nm
0.55  (0.049) 0.6  (0.053) 0.2  (0.049)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5023
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.05
Confidence Interval 95%
-0.09 to 0.19
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.34
Confidence Interval 95%
-0.48 to -0.21
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.39
Confidence Interval 95%
-0.53 to -0.25
Estimation Comments Mean Difference = Pioglitazone - metformin
13.Secondary Outcome
Title Change From Baseline in Large Low Density Lipoprotein (L3) Concentration
Hide Description The change between Large Low Density Lipoprotein collected at final visit or week 24 and Large Low Density Lipoprotein collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
96.0  (12.53) 115.7  (13.52) 18.4  (12.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2849
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 19.7
Confidence Interval 95%
-16.5 to 55.9
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -77.6
Confidence Interval 95%
-112.4 to -42.8
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -97.3
Confidence Interval 95%
-133.4 to -61.2
Estimation Comments Mean Difference = Pioglitazone - metformin
14.Secondary Outcome
Title Change From Baseline in Intermediate-Density Low Density Lipoprotein Concentration
Hide Description The change between Intermediate-Density Low Density Lipoprotein collected at final visit or week 24 and Intermediate-Density Low Density Lipoprotein collected at baseline
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
-16.3  (3.39) -11.0  (3.66) -17.3  (3.37)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2894
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.3
Confidence Interval 95%
-4.5 to 15.1
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8463
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.9
Confidence Interval 95%
-10.3 to 8.5
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2124
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.2
Confidence Interval 95%
-16.0 to 3.6
Estimation Comments Mean Difference = Pioglitazone - metformin
15.Secondary Outcome
Title Change From Baseline in Medium-Small Low Density Lipoprotein Concentration
Hide Description The change between Medium-Small Low Density Lipoprotein collected at final visit or week 24 and Medium-Small Low Density Lipoprotein collected at baseline
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
-63.8  (5.95) -66.0  (6.43) -35.3  (5.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8040
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.2
Confidence Interval 95%
-19.4 to 15.0
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 28.5
Confidence Interval 95%
12.0 to 45.0
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 30.6
Confidence Interval 95%
13.4 to 47.8
Estimation Comments Mean Difference = Pioglitazone - metformin
16.Secondary Outcome
Title Change From Baseline in Small Low Density Lipoprotein Concentration
Hide Description The change between Small Low Density Lipoprotein collected at final visit or week 24 and Small Low Density Lipoprotein collected at baseline
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
-319.3  (28.06) -321.3  (30.34) -179.0  (27.91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9604
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.1
Confidence Interval 95%
-83.3 to 79.2
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 140.3
Confidence Interval 95%
62.5 to 218.0
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 142.3
Confidence Interval 95%
61.3 to 223.3
Estimation Comments Mean Difference = Pioglitazone - metformin
17.Secondary Outcome
Title Change From Baseline in Very Small Low Density Lipoprotein Concentration
Hide Description The change between Very Small Low Density Lipoprotein collected at final visit or week 24 and Very Small Low Density Lipoprotein collected at baseline
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
-255.5  (22.37) -255.2  (24.18) -143.8  (22.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9922
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval 95%
-64.4 to 65.1
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 111.7
Confidence Interval 95%
49.7 to 173.7
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 111.4
Confidence Interval 95%
46.8 to 175.9
Estimation Comments Mean Difference = Pioglitazone - metformin
18.Secondary Outcome
Title Change From Baseline in Mean High Density Lipoprotein Particle Concentration
Hide Description The change between High Density Lipoprotein collected at final visit or week 24 and High Density Lipoprotein collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: μmol/L
0.28  (0.271) -0.80  (0.293) 0.62  (0.269)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0072
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.08
Confidence Interval 95%
-1.86 to -0.29
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3682
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.34
Confidence Interval 95%
-0.41 to 1.10
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.42
Confidence Interval 95%
0.64 to 2.20
Estimation Comments Mean Difference = Pioglitazone - metformin
19.Secondary Outcome
Title Change From Baseline in Mean High Density Lipoprotein Particle Size
Hide Description The change between High Density Lipoprotein collected at final visit or week 24 and High Density Lipoprotein collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: nm
0.15  (0.021) 0.19  (0.022) 0.11  (0.021)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1986
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.04
Confidence Interval 95%
-0.02 to 0.10
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1487
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.04
Confidence Interval 95%
-0.10 to 0.02
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0076
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.08
Confidence Interval 95%
-0.14 to -0.02
Estimation Comments Mean Difference = Pioglitazone - metformin
20.Secondary Outcome
Title Change From Baseline in Large High Density Lipoprotein (H4+H5) Concentration
Hide Description The change between Large High Density Lipoprotein collected at final visit or week 24 and Large High Density Lipoprotein collected at baseline
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: μmol/L
0.70  (1.80) 1.02  (0.194) 0.52  (0.179)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2384
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.31
Confidence Interval 95%
-0.21 to 0.83
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4617
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.19
Confidence Interval 95%
-0.69 to 0.31
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0593
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.50
Confidence Interval 95%
-1.02 to 0.02
Estimation Comments Mean Difference = Pioglitazone - metformin
21.Secondary Outcome
Title Change From Baseline in Intermediate-Medium High Density Lipoprotein (H3) Concentration
Hide Description The change between Intermediate-Medium High Density Lipoprotein collected at final visit or week 24 and Intermediate-Medium High Density Lipoprotein collected at baseline
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: μmol/L
1.34  (0.285) 1.62  (0.308) -0.09  (0.283)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5044
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.28
Confidence Interval 95%
-0.54 to 1.10
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.43
Confidence Interval 95%
-2.22 to -0.64
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.71
Confidence Interval 95%
-2.53 to -0.89
Estimation Comments Mean Difference = Pioglitazone - metformin
22.Secondary Outcome
Title Change From Baseline in Small High Density Lipoprotein (H1+H2) Concentration
Hide Description The change between Small High Density Lipoprotein collected at final visit or week 24 and Small High Density Lipoprotein collected at baseline
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: μmol/L
-1.78  (0.349) -3.41  (0.377) 0.19  (0.347)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.63
Confidence Interval 95%
-2.64 to -0.62
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.97
Confidence Interval 95%
1.01 to 2.94
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.60
Confidence Interval 95%
2.59 to 4.61
Estimation Comments Mean Difference = Pioglitazone - metformin
23.Secondary Outcome
Title Change From Baseline in Mean Very Low Density Lipoprotein Particle Concentration
Hide Description The change between Very Low Density Lipoprotein collected at final visit or week 24 and Very Low Density Lipoprotein collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
-2.78  (2.204) 0.98  (2.381) -11.30  (2.191)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2466
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.76
Confidence Interval 95%
-2.61 to 10.14
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0063
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.52
Confidence Interval 95%
-14.63 to -2.42
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
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 -12.29
Confidence Interval 95%
-18.65 to -5.93
Estimation Comments Mean Difference = Pioglitazone - metformin
24.Secondary Outcome
Title Change From Baseline in Mean Very Low Density Lipoprotein Particle Size
Hide Description The change between Very Low Density Lipoprotein collected at final visit or week 24 and Very Low Density Lipoprotein collected at baseline.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: nm
-2.64  (0.616) -3.79  (0.666) -0.20  (0.612)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2069
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.15
Confidence Interval 95%
-2.93 to 0.64
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0052
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.44
Confidence Interval 95%
0.73 to 4.15
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.59
Confidence Interval 95%
1.81 to 5.36
Estimation Comments Mean Difference = Pioglitazone - metformin
25.Secondary Outcome
Title Change From Baseline in Large-Chylomicrons Very Low Density Lipoprotein Concentration
Hide Description The change between Large-Chylomicrons Very Low Density Lipoprotein collected at final visit or week 24 and Large-Chylomicrons Very Low Density Lipoprotein collected at baseline
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
-1.71  (0.351) -1.97  (0.379) -1.96  (0.349)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6090
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.26
Confidence Interval 95%
-1.28 to 0.75
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6169
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.25
Confidence Interval 95%
-1.22 to 0.72
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9740
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.02
Confidence Interval 95%
-0.99 to 1.03
Estimation Comments Mean Difference = Pioglitazone - metformin
26.Secondary Outcome
Title Change From Baseline in Medium-Intermediate Very Low Density Lipoprotein (V3+V4) Concentration
Hide Description The change between Medium-Intermediate Very Low Density Lipoprotein collected at final visit or week 24 and Medium-Intermediate Very Low Density Lipoprotein collected at baseline
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
-4.07  (1.434) -3.01  (1.550) -6.48  (1.426)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6150
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.06
Confidence Interval 95%
-3.09 to 5.21
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2346
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.41
Confidence Interval 95%
-6.38 to 1.57
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.47
Confidence Interval 95%
-7.61 to 0.67
Estimation Comments Mean Difference = Pioglitazone - metformin
27.Secondary Outcome
Title Change From Baseline in Small Very Low Density Lipoprotein (V1+V2) Concentration
Hide Description The change between Small Very Low Density Lipoprotein collected at final visit or week 24 and Small Very Low Density Lipoprotein collected at baseline
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant must have baseline and at least one post-baseline value. LOCF for missing final/week 24 visit
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description:
Pioglitazone 15 mg/Metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Overall Number of Participants Analyzed 174 149 176
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
3.05  (1.249) 5.9  (1.350) -2.86  (1.239)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Pioglitazone 15 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1217
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.86
Confidence Interval 95%
-0.76 to 6.48
Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg/Metformin 850 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.90
Confidence Interval 95%
-9.36 to -2.44
Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg BID, Metformin 850 mg BID
Comments One-way ANCOVA with treatment as a factor and the baseline value as a covariate. LS mean change and LS mean of the treatment difference reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.76
Confidence Interval 95%
-12.36 to -5.16
Estimation Comments Mean Difference = Pioglitazone - metformin
Time Frame Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication and on or prior to 14 days after the permanent discontinuation of the double-blind study medication.
Adverse Event Reporting Description One participant was randomized to Metformin 850 mg but inadvertently received Pioglitazone 15 mg. Analyses performed on Efficacy Variables were based on Randomized Treatment; analyses on Safety Variables were based on Actual Treatment Received.
 
Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Hide Arm/Group Description Pioglitazone 15 mg /metformin 850 mg combination tablets, orally, twice daily for up to 24 weeks Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
All-Cause Mortality
Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/201 (1.00%)   3/190 (1.58%)   5/209 (2.39%) 
Blood and lymphatic system disorders       
Leukocytosis  1  0/201 (0.00%)  0/190 (0.00%)  1/209 (0.48%) 
Cardiac disorders       
Acute myocardial infarction  1  0/201 (0.00%)  1/190 (0.53%)  0/209 (0.00%) 
Gastrointestinal disorders       
Diverticulum intestinal  1  1/201 (0.50%)  0/190 (0.00%)  0/209 (0.00%) 
Hepatobiliary disorders       
Cholecystitis chronic  1  0/201 (0.00%)  0/190 (0.00%)  1/209 (0.48%) 
Infections and infestations       
Cellulitis  1  0/201 (0.00%)  0/190 (0.00%)  1/209 (0.48%) 
Diverticulitis  1  0/201 (0.00%)  0/190 (0.00%)  1/209 (0.48%) 
Injury, poisoning and procedural complications       
Fall  1  0/201 (0.00%)  0/190 (0.00%)  1/209 (0.48%) 
Metabolism and nutrition disorders       
Hyperglycemia  1  0/201 (0.00%)  1/190 (0.53%)  0/209 (0.00%) 
Hypoglycemia  1  1/201 (0.50%)  0/190 (0.00%)  0/209 (0.00%) 
Reproductive system and breast disorders       
Endometriosis  1  0/201 (0.00%)  1/190 (0.53%)  0/209 (0.00%) 
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 3%
Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   84/201 (41.79%)   61/190 (32.11%)   95/209 (45.45%) 
Gastrointestinal disorders       
Diarrhoea  1  18/201 (8.96%)  5/190 (2.63%)  32/209 (15.31%) 
Abdominal pain  1  4/201 (1.99%)  3/190 (1.58%)  7/209 (3.35%) 
General disorders       
Oedema Peripheral  1  6/201 (2.99%)  8/190 (4.21%)  3/209 (1.44%) 
Infections and infestations       
Pharyngitis  1  8/201 (3.98%)  5/190 (2.63%)  7/209 (3.35%) 
Urinary tract infection  1  6/201 (2.99%)  5/190 (2.63%)  9/209 (4.31%) 
Nasopharyngitis  1  8/201 (3.98%)  3/190 (1.58%)  5/209 (2.39%) 
Bronchitis  1  5/201 (2.49%)  7/190 (3.68%)  3/209 (1.44%) 
Investigations       
Glycosylated haemoglobin  1  2/201 (1.00%)  7/190 (3.68%)  7/209 (3.35%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  4/201 (1.99%)  8/190 (4.21%)  6/209 (2.87%) 
Nervous system disorders       
Headache  1  11/201 (5.47%)  5/190 (2.63%)  10/209 (4.78%) 
Dizziness  1  6/201 (2.99%)  3/190 (1.58%)  4/209 (1.91%) 
Psychiatric disorders       
Insomnia  1  6/201 (2.99%)  2/190 (1.05%)  2/209 (0.96%) 
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 sponsor can review results communications prior to public release and can embargo trial results communications up to 150 days to permit actions necessary to preserve sponsor's intellectual property. Sponsor can request changes to the results communication only for the purpose of removing non study related information that is proprietary and confidential to sponsor. Sponsor can require delay of a results communication until the study has been completed at all participating sites.
Results Point of Contact
Name/Title: Sr. VP Clinical Science
Organization: Takeda Global Research and Development Center, Inc.
Phone: 800-778-2860
Responsible Party: Sr. VP, Clinical Science, Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier: NCT00727857     History of Changes
Other Study ID Numbers: 01-06-TL-OPIMET-008
U1111-1114-0371 ( Registry Identifier: WHO )
First Submitted: July 30, 2008
First Posted: August 4, 2008
Results First Submitted: August 28, 2009
Results First Posted: March 9, 2010
Last Update Posted: July 29, 2011