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

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT00727857
Collaborator
(none)
600
Enrollment
77
Locations
3
Arms
14
Duration (Months)
7.8
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy of pioglitazone, twice daily (BID), combined with metformin versus pioglitazone taken alone and metformin taken alone in treating Type 2 Diabetes Mellitus.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Pioglitazone hydrochloride (ACTOS®) is a member of a class of oral antidiabetic agents known as thiazolidinediones, which act by reducing insulin resistance. Insulin resistance is a key feature of dysmetabolic syndrome and has been suggested to be the common pathophysiologic basis of both atherosclerosis and type 2 diabetes. Pioglitazone binds to peroxisome proliferator-activated receptors, an effect that is associated with altered transcription of genes capable of influencing carbohydrate and lipid metabolism.

Metformin hydrochloride is an oral antihyperglycemic drug not chemically or pharmacologically related to thiazolidinediones. Metformin is a biguanide, which has been shown to be effective in improving glycemic control in diabetic patients. Metformin inhibits hepatic glucose production, most likely through an inhibition of gluconeogenesis, and its use is associated with an improvement in tissue sensitivity to insulin. In accordance with published algorithms for the use of combination therapy for the treatment of type 2 diabetes, physicians have traditionally combined metformin with other antidiabetic agents.

This study will determine the effect of a fixed-dose combination of metformin with pioglitazone, compared to metformin monotherapy and pioglitazone monotherapy.

Study participation is anticipated to be approximately 6.5 months.

Study Design

Study Type:
Interventional
Actual Enrollment :
600 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3b, Double-Blind, Randomized Study to Determine the Efficacy and Safety of Pioglitazone HCl and Metformin HCl Fixed-Dose Combination Therapy Compared to Pioglitazone HCl Monotherapy and to Metformin HCl Monotherapy in the Treatment of Subjects With Type 2 Diabetes
Study Start Date :
Jun 1, 2007
Actual Primary Completion Date :
Aug 1, 2008
Actual Study Completion Date :
Aug 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pioglitazone 15 mg /Metformin 850 mg BID

Drug: Pioglitazone and metformin
Pioglitazone 15 mg /metformin 850 mg combination, tablets, orally, twice daily for up to 24 weeks.
Other Names:
  • ACTOPLUS MET

    		•
    Active Comparator: Pioglitazone 15 mg BID

    Drug: Pioglitazone
    Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks.
    Other Names:
  • ACTOS®
  • AD4833

    		•
    Active Comparator: Metformin 850 mg BID

    Drug: Metformin
    Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
    Other Names:
  • Fortamet
  • Glucophage
  • Glucophage XR
  • Glumetza
  • Riomet

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percent Change From Baseline in Glycosylated Hemoglobin [Baseline and Week 24]

      The change between the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at final visit or week 24 and Glycosylated Hemoglobin collected at baseline.

    Secondary Outcome Measures

    1. Change From Baseline in Fasting Plasma Glucose [Baseline and Week 24]

      The change between the value of Fasting Plasma Glucose collected at final visit or week 24 and Fasting Plasma Glucose collected at baseline.

    2. Change From Baseline in Fasting Insulin [Baseline and Week 24]

      The change between the Fasting Insulin value collected at final visit or week 24 and Fasting Insulin collected at baseline.

    3. Change From Baseline in Homeostasis Model Assessment - Insulin Resistance [Baseline and Week 24]

      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).

    4. Median Percent Change From Baseline in High Sensitivity C-reactive Protein [Baseline and Week 24]

      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

    5. Change From Baseline in Adiponectin [Baseline and Week 24]

      The change between Adiponectin collected at final visit or week 24 and Adiponectin collected at baseline.

    6. Change From Baseline in Total Cholesterol [Baseline and Week 24]

      The change between Total Cholesterol collected at final visit or week 24 and Total Cholesterol collected at baseline.

    7. Change From Baseline in Low-Density Lipoprotein Cholesterol [Baseline and Week 24]

      The change between Low-Density Lipoprotein Cholesterol collected at final visit or week 24 and Low-Density Lipoprotein Cholesterol collected at baseline.

    8. Change From Baseline in High-Density Lipoprotein Cholesterol [Baseline and Week 24]

      The change between High-Density Lipoprotein Cholesterol collected at final visit or week 24 and High-Density Lipoprotein Cholesterol collected at baseline.

    9. Change From Baseline in Triglycerides [Baseline and Week 24]

      The change between Triglycerides collected at final visit or week 24 and Triglycerides collected at baseline.

    10. Change From Baseline in Mean Low Density Lipoprotein Particle Concentration [Baseline and Week 24]

      The change between Low Density Lipoprotein particle concentration collected at final visit or week 24 and Low Density Lipoprotein particle concentration collected at baseline.

    11. Change From Baseline in Mean Low Density Lipoprotein Particle Size [Baseline and Week 24]

      The change between Low Density Lipoprotein collected at final visit or week 24 and Low Density Lipoprotein collected at baseline.

    12. Change From Baseline in Large Low Density Lipoprotein (L3) Concentration [Baseline and Week 24]

      The change between Large Low Density Lipoprotein collected at final visit or week 24 and Large Low Density Lipoprotein collected at baseline.

    13. Change From Baseline in Intermediate-Density Low Density Lipoprotein Concentration [Baseline and Week 24]

      The change between Intermediate-Density Low Density Lipoprotein collected at final visit or week 24 and Intermediate-Density Low Density Lipoprotein collected at baseline

    14. Change From Baseline in Medium-Small Low Density Lipoprotein Concentration [Baseline and Week 24]

      The change between Medium-Small Low Density Lipoprotein collected at final visit or week 24 and Medium-Small Low Density Lipoprotein collected at baseline

    15. Change From Baseline in Small Low Density Lipoprotein Concentration [Baseline and Week 24]

      The change between Small Low Density Lipoprotein collected at final visit or week 24 and Small Low Density Lipoprotein collected at baseline

    16. Change From Baseline in Very Small Low Density Lipoprotein Concentration [Baseline and Week 24]

      The change between Very Small Low Density Lipoprotein collected at final visit or week 24 and Very Small Low Density Lipoprotein collected at baseline

    17. Change From Baseline in Mean High Density Lipoprotein Particle Concentration [Baseline and Week 24]

      The change between High Density Lipoprotein collected at final visit or week 24 and High Density Lipoprotein collected at baseline.

    18. Change From Baseline in Mean High Density Lipoprotein Particle Size [Baseline and Week 24]

      The change between High Density Lipoprotein collected at final visit or week 24 and High Density Lipoprotein collected at baseline.

    19. Change From Baseline in Large High Density Lipoprotein (H4+H5) Concentration [Baseline and Week 24]

      The change between Large High Density Lipoprotein collected at final visit or week 24 and Large High Density Lipoprotein collected at baseline

    20. Change From Baseline in Intermediate-Medium High Density Lipoprotein (H3) Concentration [Baseline and Week 24]

      The change between Intermediate-Medium High Density Lipoprotein collected at final visit or week 24 and Intermediate-Medium High Density Lipoprotein collected at baseline

    21. Change From Baseline in Small High Density Lipoprotein (H1+H2) Concentration [Baseline and Week 24]

      The change between Small High Density Lipoprotein collected at final visit or week 24 and Small High Density Lipoprotein collected at baseline

    22. Change From Baseline in Mean Very Low Density Lipoprotein Particle Concentration [Baseline and Week 24]

      The change between Very Low Density Lipoprotein collected at final visit or week 24 and Very Low Density Lipoprotein collected at baseline.

    23. Change From Baseline in Mean Very Low Density Lipoprotein Particle Size [Baseline and Week 24]

      The change between Very Low Density Lipoprotein collected at final visit or week 24 and Very Low Density Lipoprotein collected at baseline.

    24. Change From Baseline in Large-Chylomicrons Very Low Density Lipoprotein Concentration [Baseline and Week 24]

      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

    25. Change From Baseline in Medium-Intermediate Very Low Density Lipoprotein (V3+V4) Concentration [Baseline and Week 24]

      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

    26. Change From Baseline in Small Very Low Density Lipoprotein (V1+V2) Concentration [Baseline and Week 24]

      The change between Small Very Low Density Lipoprotein collected at final visit or week 24 and Small Very Low Density Lipoprotein collected at baseline

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    • Has type 2 diabetes.

    • Has received no treatment with antidiabetic medication in the 12 weeks prior to Screening, other than short-term use defined as less than or equal to 15 days.

    • A glycosylated hemoglobin greater than or equal to 7.5% and less than or equal to 10.0% at Screening.

    • Body mass index less than or equal to 45 kg/m2.

    • Has received counseling on lifestyle modification for type 2 diabetes, including diet and exercise.

    • Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

    • Stable condition as determined by a physician.

    Exclusion Criteria

    • Type 1 diabetes.

    • Unstable angina or heart failure of any etiology with New York Heart Association functional class III or IV.

    • History of myocardial infarction, cerebrovascular accident, percutaneous coronary intervention, coronary artery bypass graft, or transient ischemic attack in the 6 months prior to Screening.

    • Male participant has a serum creatinine level greater than or equal to 1.5 mg per dL or female subject has a serum creatinine level greater than or equal to 1.4 mg per dL.

    • Has a triglyceride level greater than 500 mg per dL.

    • Male participant has a hemoglobin level less than 10.5 g per dL or female subject has a hemoglobin level less than 10.0 g per dL.

    • Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.

    • History of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per day) within 2 years prior to Screening.

    • Has been discontinued from a thiazolidinedione or metformin therapy due to lack of efficacy or clinical or laboratory signs of intolerance.

    • Previous history of cancer, other than basal cell or stage 1 squamous cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study medication.

    • History of acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma.

    • Any disease or condition at Screening or Randomization that would compromise safety, might affect life expectancy, or make it difficult to successfully manage and follow the subject according to the protocol.

    • Currently participating in another investigational study or has participated in an investigational study within 30 days prior to randomization.

    • Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

    • Antidiabetic medications other than study medication

    • Chronically used oral or parenteral glucocorticoids

    • Niacin greater than 200 mg per day, including niacin-containing products such as Advicor

    • Chronically used steroid-joint injections

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States
    2 Haleyville Alabama United States
    3 Montgomery Alabama United States
    4 Pell City Alabama United States
    5 Phoenix Arizona United States
    6 Tucson Arizona United States
    7 Anaheim California United States
    8 Artesia California United States
    9 Dinuba California United States
    10 Long Beach California United States
    11 Los Angeles, California United States
    12 Norwalk California United States
    13 Orange California United States
    14 Santa Ana California United States
    15 Santa Monica California United States
    16 Pueblo Colorado United States
    17 Altamonte Springs Florida United States
    18 Coral Gables Florida United States
    19 Hialeah Florida United States
    20 Miami, Florida United States
    21 Panama City Florida United States
    22 Plantation Florida United States
    23 St Petersburg Florida United States
    24 St. Cloud Florida United States
    25 Tampa Florida United States
    26 Columbus Georgia United States
    27 Boise Idaho United States
    28 Coeur d' Alene, Idaho United States
    29 Chicago Illinois United States
    30 Flossmoor Illinois United States
    31 Peoria Illinois United States
    32 Elkhart Indiana United States
    33 Shawnee, Kansas United States
    34 Southfield Michigan United States
    35 Chesterfield Missouri United States
    36 Billings Montana United States
    37 Elizabeth New Jersey United States
    38 Fayetteville New York United States
    39 New York New York United States
    40 Durham North Carolina United States
    41 Pinehurst North Carolina United States
    42 Cincinnati Ohio United States
    43 Perrysburg Ohio United States
    44 Zanesville Ohio United States
    45 Oklahoma City Oklahoma United States
    46 Eugene Oregon United States
    47 Fleetwood Pennsylvania United States
    48 Norristown Pennsylvania United States
    49 Cranston Rhode Island United States
    50 Simpsonville, South Carolina United States
    51 Varnville South Carolina United States
    52 Fayetteville Tennessee United States
    53 Corpus Christi Texas United States
    54 Dallas Texas United States
    55 El Paso Texas United States
    56 Houston Texas United States
    57 McAllen Texas United States
    58 Mission Texas United States
    59 New Braunfels Texas United States
    60 North Richland Hills Texas United States
    61 San Antonio, Texas United States
    62 Bountiful Utah United States
    63 Salt Lake City Utah United States
    64 Petersburg Virginia United States
    65 Port Orchard Washington United States
    66 Spokane Washington United States
    67 Providencia-Santiago Chile
    68 Temuco Chile
    69 Zapopan Jalisco Mexico
    70 Monterrey Nuevo Leon Mexico
    71 Aibonito Puerto Rico
    72 Caguas Puerto Rico
    73 Ciales Puerto Rico
    74 Coto Laurel Puerto Rico
    75 Guayma Puerto Rico
    76 Guaynabo Puerto Rico
    77 Rio Piedras Puerto Rico

    Sponsors and Collaborators

    • Takeda

    Investigators

    • Study Director: VP Clinical Science Strategy, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00727857
    Other Study ID Numbers:
    • 01-06-TL-OPIMET-008
    • U1111-1114-0371
    First Posted:
    Aug 4, 2008
    Last Update Posted:
    Jul 29, 2011
    Last Verified:
    Jul 1, 2011
    Keywords provided by , ,
    Glucose Metabolism Disorder
    Dysmetabolic Syndrome
    Type II Diabetes
    Diabetes Mellitus, Lipoatrophic
    Dyslipidemia
    Drug Therapy
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Metformin
    Pioglitazone

    Study Results

    Participant Flow

    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 Detail 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
    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

    Baseline Characteristics

    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID Total
    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 Participants 201 189 210 600
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    54.7
    (12.23)
    54.0
    (12.08)
    53.7
    (12.00)
    54.1
    (12.09)
    Sex: Female, Male (Count of 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 (participants) [Number]
    American Indian or Alaska Native
    2
    1%
    6
    3.2%
    6
    2.9%
    14
    2.3%
    Asian
    3
    1.5%
    5
    2.6%
    5
    2.4%
    13
    2.2%
    Black or African American
    12
    6%
    13
    6.9%
    14
    6.7%
    39
    6.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    123
    61.2%
    109
    57.7%
    124
    59%
    356
    59.3%
    Multiracial
    61
    30.3%
    56
    29.6%
    61
    29%
    178
    29.7%
    Body Mass Index (kg/m²) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m²]
    30.84
    (5.74)
    31.18
    (5.50)
    30.83
    (5.66)
    30.94
    (5.63)

    Outcome Measures

    1. Primary Outcome
    Title Percent Change From Baseline in Glycosylated Hemoglobin
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 188 162 193
    Least Squares Mean (Standard Error) [percentage of Glycosylated Hemoglobin]
    -1.83
    (0.122)
    -0.96
    (0.131)
    -0.99
    (0.120)
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.86
    Confidence Interval () 95%
    0.51 to 1.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.84
    Confidence Interval () 95%
    0.50 to 1.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.8919
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.02
    Confidence Interval () 95%
    -0.37 to 0.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    2. Secondary Outcome
    Title Change From Baseline in Fasting Plasma Glucose
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 196 176 202
    Least Squares Mean (Standard Error) [mg/dL]
    -39.9
    (3.48)
    -22.2
    (3.67)
    -24.8
    (3.42)
    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
    Statistical Test of Hypothesis p-Value 0.0005
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 17.8
    Confidence Interval () 95%
    7.8 to 27.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.0021
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 15.1
    Confidence Interval () 95%
    5.5 to 24.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.5981
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.6
    Confidence Interval () 95%
    -12.5 to 7.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    3. Secondary Outcome
    Title Change From Baseline in Fasting Insulin
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 178 146 185
    Least Squares Mean (Standard Error) [ÎĽIU/mL]
    -3.91
    (0.736)
    -3.18
    (0.812)
    -0.98
    (0.722)
    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
    Statistical Test of Hypothesis p-Value 0.5074
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.73
    Confidence Interval () 95%
    -1.43 to 2.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.0047
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.93
    Confidence Interval () 95%
    0.90 to 4.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.0435
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.20
    Confidence Interval () 95%
    0.06 to 4.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    4. Secondary Outcome
    Title Change From Baseline in Homeostasis Model Assessment - Insulin Resistance
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 160 139 172
    Least Squares Mean (Standard Error) [percent of insulin resistance]
    -2.704
    (0.4274)
    -2.075
    (0.4586)
    -1.085
    (0.4123)
    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
    Statistical Test of Hypothesis p-Value 0.3158
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.629
    Confidence Interval () 95%
    -0.602 to 1.861
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.0067
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.619
    Confidence Interval () 95%
    0.452 to 2.785
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.1094
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.989
    Confidence Interval () 95%
    -0.223 to 2.201
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    5. Secondary Outcome
    Title Median Percent Change From Baseline in High Sensitivity C-reactive Protein
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 190 168 196
    Median (Full Range) [percent]
    -36.7
    (4.6719)
    -34.0
    (8.1275)
    -26.2
    (12.5526)
    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
    Statistical Test of Hypothesis p-Value 0.5963
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Median Difference (Final Values)
    Estimated Value 4.88
    Confidence Interval () 95%
    -4.71 to 13.97
    Parameter Dispersion Type:
    Value:
    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.
    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
    Statistical Test of Hypothesis p-Value 0.0265
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Median Difference (Final Values)
    Estimated Value 12.81
    Confidence Interval () 95%
    2.88 to 22.24
    Parameter Dispersion Type:
    Value:
    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.
    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
    Statistical Test of Hypothesis p-Value 0.1053
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Median Difference (Final Values)
    Estimated Value 8.33
    Confidence Interval () 95%
    -1.77 to 18.07
    Parameter Dispersion Type:
    Value:
    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
    Description The change between Adiponectin collected at final visit or week 24 and Adiponectin collected at baseline.
    Time Frame Baseline and Week 24

    Outcome Measure Data

    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
    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.
    Measure Participants 179 148 183
    Least Squares Mean (Standard Error) [mcg/ml]
    7.8
    (0.55)
    9.2
    (0.61)
    -0.3
    (0.55)
    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
    Statistical Test of Hypothesis p-Value 0.0806
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.4
    Confidence Interval () 95%
    -0.2 to 3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.1
    Confidence Interval () 95%
    -9.6 to -6.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -9.5
    Confidence Interval () 95%
    -11.1 to -7.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    7. Secondary Outcome
    Title Change From Baseline in Total Cholesterol
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 178 154 182
    Least Squares Mean (Standard Error) [mg/dL]
    1.06
    (1.183)
    4.79
    (1.271)
    -2.72
    (1.169)
    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
    Statistical Test of Hypothesis p-Value 0.0324
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.73
    Confidence Interval () 95%
    0.31 to 7.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.0233
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.78
    Confidence Interval () 95%
    -7.05 to -0.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -7.51
    Confidence Interval () 95%
    -10.90 to -4.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    8. Secondary Outcome
    Title Change From Baseline in Low-Density Lipoprotein Cholesterol
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 177 152 180
    Least Squares Mean (Standard Error) [mg/dL]
    1.19
    (2.015)
    6.08
    (2.175)
    -1.37
    (1.998)
    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
    Statistical Test of Hypothesis p-Value 0.0993
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.90
    Confidence Interval () 95%
    -0.93 to 10.72
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.3670
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.56
    Confidence Interval () 95%
    -8.14 to 3.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.0119
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -7.46
    Confidence Interval () 95%
    -13.26 to -1.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    9. Secondary Outcome
    Title Change From Baseline in High-Density Lipoprotein Cholesterol
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 177 152 180
    Least Squares Mean (Standard Error) [mg/dL]
    14.20
    (1.440)
    9.88
    (1.552)
    6.09
    (1.426)
    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
    Statistical Test of Hypothesis p-Value 0.0423
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.31
    Confidence Interval () 95%
    -8.48 to -0.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.10
    Confidence Interval () 95%
    -12.08 to -4.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.728
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.79
    Confidence Interval () 95%
    -7.93 to 0.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    10. Secondary Outcome
    Title Change From Baseline in Triglycerides
    Description The change between Triglycerides collected at final visit or week 24 and Triglycerides collected at baseline.
    Time Frame Baseline and Week 24

    Outcome Measure Data

    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
    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.
    Measure Participants 180 157 184
    Least Squares Mean (Standard Error) [mg/dL]
    -5.95
    (2.901)
    -5.54
    (3.107)
    -1.78
    (2.871)
    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
    Statistical Test of Hypothesis p-Value 0.9231
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.41
    Confidence Interval () 95%
    -7.94 to 8.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.3082
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.16
    Confidence Interval () 95%
    -3.86 to 12.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.3753
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.75
    Confidence Interval () 95%
    -4.56 to 12.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    11. Secondary Outcome
    Title Change From Baseline in Mean Low Density Lipoprotein Particle Concentration
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [nmol/L]
    -240.6
    (23.50)
    -217.2
    (25.40)
    -176.4
    (23.36)
    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
    Statistical Test of Hypothesis p-Value 0.4999
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 23.4
    Confidence Interval () 95%
    -44.6 to 91.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.0531
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 64.2
    Confidence Interval () 95%
    -0.9 to 129.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.2369
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 40.9
    Confidence Interval () 95%
    -26.9 to 108.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    12. Secondary Outcome
    Title Change From Baseline in Mean Low Density Lipoprotein Particle Size
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Deviation) [nm]
    0.55
    (0.049)
    0.6
    (0.053)
    0.2
    (0.049)
    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
    Statistical Test of Hypothesis p-Value 0.5023
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.05
    Confidence Interval () 95%
    -0.09 to 0.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.34
    Confidence Interval () 95%
    -0.48 to -0.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.39
    Confidence Interval () 95%
    -0.53 to -0.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    13. Secondary Outcome
    Title Change From Baseline in Large Low Density Lipoprotein (L3) Concentration
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [nmol/L]
    96.0
    (12.53)
    115.7
    (13.52)
    18.4
    (12.46)
    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
    Statistical Test of Hypothesis p-Value 0.2849
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 19.7
    Confidence Interval () 95%
    -16.5 to 55.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -77.6
    Confidence Interval () 95%
    -112.4 to -42.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -97.3
    Confidence Interval () 95%
    -133.4 to -61.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    14. Secondary Outcome
    Title Change From Baseline in Intermediate-Density Low Density Lipoprotein Concentration
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [nmol/L]
    -16.3
    (3.39)
    -11.0
    (3.66)
    -17.3
    (3.37)
    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
    Statistical Test of Hypothesis p-Value 0.2894
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.3
    Confidence Interval () 95%
    -4.5 to 15.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.8463
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.9
    Confidence Interval () 95%
    -10.3 to 8.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.2124
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -6.2
    Confidence Interval () 95%
    -16.0 to 3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    15. Secondary Outcome
    Title Change From Baseline in Medium-Small Low Density Lipoprotein Concentration
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [nmol/L]
    -63.8
    (5.95)
    -66.0
    (6.43)
    -35.3
    (5.92)
    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
    Statistical Test of Hypothesis p-Value 0.8040
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.2
    Confidence Interval () 95%
    -19.4 to 15.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.0008
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 28.5
    Confidence Interval () 95%
    12.0 to 45.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.0005
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 30.6
    Confidence Interval () 95%
    13.4 to 47.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    16. Secondary Outcome
    Title Change From Baseline in Small Low Density Lipoprotein Concentration
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [nmol/L]
    -319.3
    (28.06)
    -321.3
    (30.34)
    -179.0
    (27.91)
    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
    Statistical Test of Hypothesis p-Value 0.9604
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.1
    Confidence Interval () 95%
    -83.3 to 79.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.0004
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 140.3
    Confidence Interval () 95%
    62.5 to 218.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.0006
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 142.3
    Confidence Interval () 95%
    61.3 to 223.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    17. Secondary Outcome
    Title Change From Baseline in Very Small Low Density Lipoprotein Concentration
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [nmol/L]
    -255.5
    (22.37)
    -255.2
    (24.18)
    -143.8
    (22.25)
    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
    Statistical Test of Hypothesis p-Value 0.9922
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.3
    Confidence Interval () 95%
    -64.4 to 65.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.0004
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 111.7
    Confidence Interval () 95%
    49.7 to 173.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.0008
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 111.4
    Confidence Interval () 95%
    46.8 to 175.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    18. Secondary Outcome
    Title Change From Baseline in Mean High Density Lipoprotein Particle Concentration
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [ÎĽmol/L]
    0.28
    (0.271)
    -0.80
    (0.293)
    0.62
    (0.269)
    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
    Statistical Test of Hypothesis p-Value 0.0072
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.08
    Confidence Interval () 95%
    -1.86 to -0.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.3682
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.34
    Confidence Interval () 95%
    -0.41 to 1.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.0004
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.42
    Confidence Interval () 95%
    0.64 to 2.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    19. Secondary Outcome
    Title Change From Baseline in Mean High Density Lipoprotein Particle Size
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [nm]
    0.15
    (0.021)
    0.19
    (0.022)
    0.11
    (0.021)
    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
    Statistical Test of Hypothesis p-Value 0.1986
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.04
    Confidence Interval () 95%
    -0.02 to 0.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.1487
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.04
    Confidence Interval () 95%
    -0.10 to 0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.0076
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.08
    Confidence Interval () 95%
    -0.14 to -0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    20. Secondary Outcome
    Title Change From Baseline in Large High Density Lipoprotein (H4+H5) Concentration
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [ÎĽmol/L]
    0.70
    (1.80)
    1.02
    (0.194)
    0.52
    (0.179)
    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
    Statistical Test of Hypothesis p-Value 0.2384
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.31
    Confidence Interval () 95%
    -0.21 to 0.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.4617
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.19
    Confidence Interval () 95%
    -0.69 to 0.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.0593
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.50
    Confidence Interval () 95%
    -1.02 to 0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    21. Secondary Outcome
    Title Change From Baseline in Intermediate-Medium High Density Lipoprotein (H3) Concentration
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [ÎĽmol/L]
    1.34
    (0.285)
    1.62
    (0.308)
    -0.09
    (0.283)
    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
    Statistical Test of Hypothesis p-Value 0.5044
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.28
    Confidence Interval () 95%
    -0.54 to 1.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.0004
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.43
    Confidence Interval () 95%
    -2.22 to -0.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.71
    Confidence Interval () 95%
    -2.53 to -0.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    22. Secondary Outcome
    Title Change From Baseline in Small High Density Lipoprotein (H1+H2) Concentration
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [ÎĽmol/L]
    -1.78
    (0.349)
    -3.41
    (0.377)
    0.19
    (0.347)
    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
    Statistical Test of Hypothesis p-Value 0.0017
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.63
    Confidence Interval () 95%
    -2.64 to -0.62
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.97
    Confidence Interval () 95%
    1.01 to 2.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.60
    Confidence Interval () 95%
    2.59 to 4.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    23. Secondary Outcome
    Title Change From Baseline in Mean Very Low Density Lipoprotein Particle Concentration
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [nmol/L]
    -2.78
    (2.204)
    0.98
    (2.381)
    -11.30
    (2.191)
    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
    Statistical Test of Hypothesis p-Value 0.2466
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.76
    Confidence Interval () 95%
    -2.61 to 10.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.0063
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.52
    Confidence Interval () 95%
    -14.63 to -2.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.0002
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.29
    Confidence Interval () 95%
    -18.65 to -5.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    24. Secondary Outcome
    Title Change From Baseline in Mean Very Low Density Lipoprotein Particle Size
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [nm]
    -2.64
    (0.616)
    -3.79
    (0.666)
    -0.20
    (0.612)
    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
    Statistical Test of Hypothesis p-Value 0.2069
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.15
    Confidence Interval () 95%
    -2.93 to 0.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.0052
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.44
    Confidence Interval () 95%
    0.73 to 4.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.59
    Confidence Interval () 95%
    1.81 to 5.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    25. Secondary Outcome
    Title Change From Baseline in Large-Chylomicrons Very Low Density Lipoprotein Concentration
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [nmol/L]
    -1.71
    (0.351)
    -1.97
    (0.379)
    -1.96
    (0.349)
    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
    Statistical Test of Hypothesis p-Value 0.6090
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.26
    Confidence Interval () 95%
    -1.28 to 0.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.6169
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.25
    Confidence Interval () 95%
    -1.22 to 0.72
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.9740
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.02
    Confidence Interval () 95%
    -0.99 to 1.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    26. Secondary Outcome
    Title Change From Baseline in Medium-Intermediate Very Low Density Lipoprotein (V3+V4) Concentration
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [nmol/L]
    -4.07
    (1.434)
    -3.01
    (1.550)
    -6.48
    (1.426)
    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
    Statistical Test of Hypothesis p-Value 0.6150
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.06
    Confidence Interval () 95%
    -3.09 to 5.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.2346
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.41
    Confidence Interval () 95%
    -6.38 to 1.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value 0.1001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.47
    Confidence Interval () 95%
    -7.61 to 0.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin
    27. Secondary Outcome
    Title Change From Baseline in Small Very Low Density Lipoprotein (V1+V2) Concentration
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 174 149 176
    Least Squares Mean (Standard Error) [nmol/L]
    3.05
    (1.249)
    5.9
    (1.350)
    -2.86
    (1.239)
    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
    Statistical Test of Hypothesis p-Value 0.1217
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.86
    Confidence Interval () 95%
    -0.76 to 6.48
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - pioglitazone
    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
    Statistical Test of Hypothesis p-Value 0.0009
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -5.90
    Confidence Interval () 95%
    -9.36 to -2.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone & metformin - metformin
    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
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.76
    Confidence Interval () 95%
    -12.36 to -5.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference = Pioglitazone - metformin

    Adverse Events

    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
    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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/201 (1%) 3/190 (1.6%) 5/209 (2.4%)
    Blood and lymphatic system disorders
    Leukocytosis 0/201 (0%) 0/190 (0%) 1/209 (0.5%)
    Cardiac disorders
    Acute myocardial infarction 0/201 (0%) 1/190 (0.5%) 0/209 (0%)
    Gastrointestinal disorders
    Diverticulum intestinal 1/201 (0.5%) 0/190 (0%) 0/209 (0%)
    Hepatobiliary disorders
    Cholecystitis chronic 0/201 (0%) 0/190 (0%) 1/209 (0.5%)
    Infections and infestations
    Cellulitis 0/201 (0%) 0/190 (0%) 1/209 (0.5%)
    Diverticulitis 0/201 (0%) 0/190 (0%) 1/209 (0.5%)
    Injury, poisoning and procedural complications
    Fall 0/201 (0%) 0/190 (0%) 1/209 (0.5%)
    Metabolism and nutrition disorders
    Hyperglycemia 0/201 (0%) 1/190 (0.5%) 0/209 (0%)
    Hypoglycemia 1/201 (0.5%) 0/190 (0%) 0/209 (0%)
    Reproductive system and breast disorders
    Endometriosis 0/201 (0%) 1/190 (0.5%) 0/209 (0%)
    Other (Not Including Serious) Adverse Events
    Pioglitazone 15 mg/Metformin 850 mg BID Pioglitazone 15 mg BID Metformin 850 mg BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 84/201 (41.8%) 61/190 (32.1%) 95/209 (45.5%)
    Gastrointestinal disorders
    Diarrhoea 18/201 (9%) 5/190 (2.6%) 32/209 (15.3%)
    Abdominal pain 4/201 (2%) 3/190 (1.6%) 7/209 (3.3%)
    General disorders
    Oedema Peripheral 6/201 (3%) 8/190 (4.2%) 3/209 (1.4%)
    Infections and infestations
    Pharyngitis 8/201 (4%) 5/190 (2.6%) 7/209 (3.3%)
    Urinary tract infection 6/201 (3%) 5/190 (2.6%) 9/209 (4.3%)
    Nasopharyngitis 8/201 (4%) 3/190 (1.6%) 5/209 (2.4%)
    Bronchitis 5/201 (2.5%) 7/190 (3.7%) 3/209 (1.4%)
    Investigations
    Glycosylated haemoglobin 2/201 (1%) 7/190 (3.7%) 7/209 (3.3%)
    Musculoskeletal and connective tissue disorders
    Back pain 4/201 (2%) 8/190 (4.2%) 6/209 (2.9%)
    Nervous system disorders
    Headache 11/201 (5.5%) 5/190 (2.6%) 10/209 (4.8%)
    Dizziness 6/201 (3%) 3/190 (1.6%) 4/209 (1.9%)
    Psychiatric disorders
    Insomnia 6/201 (3%) 2/190 (1.1%) 2/209 (1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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
    Email clinicaltrialregistry@tpna.com
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00727857
    Other Study ID Numbers:
    • 01-06-TL-OPIMET-008
    • U1111-1114-0371
    First Posted:
    Aug 4, 2008
    Last Update Posted:
    Jul 29, 2011
    Last Verified:
    Jul 1, 2011