Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of Metformin Hydrochloride (HCl) in Combination With Colesevelam HCl, Compared to Metformin HCl Alone, in Patients With Type 2 Diabetes Mellitus and the Effects of Colesevelam HCl on Lipids and Glucose on Pre-diabetic Patients.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00570739
Recruitment Status : Completed
First Posted : December 11, 2007
Results First Posted : July 13, 2010
Last Update Posted : July 27, 2010
Sponsor:
Information provided by:
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Type 2 Diabetes Mellitus
Hypercholesterolemia
Pre-diabetes
Interventions Drug: Metformin HCl and Colesevelam Placebo
Drug: Metformin HCl tablets and Colesevelam tablets
Drug: Colesevelam placebo
Drug: Colesevelam
Enrollment 502
Recruitment Details Two cohorts of participants, type 2 diabetics (T2DM) and pre-diabetics, were recruited from 07 Jan 2008 to 15 Dec 2008. The sites were located in Colombia, India, Mexico, and the USA. The sites included private physician offices, group practices, clinics, hospitals, institutes, and university centers.
Pre-assignment Details Due to the different metabolic nature of the two groups the "Total" column under Baseline Characteristics is populated with data for the diabetic group, except where the total could be obtained by just adding the number of participants. Please note: in the outcomes section, LOCF=Last Observation carried forward
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin Pre-diabetic Group: Placebo Pre-diabetic Group: Colesevelam
Hide Arm/Group Description This group received 6 matching colesevalm placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. This treatment duration was 16 weeks. This group received 6 colevevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. This treatment duration was 16 weeks. This group was given 6 placebo tablets once a day. They matched the colesevelam tablets. This treatment duration was 16 weeks. This group was given 6 colesevelam tablets, 625mg, once a day. This treatment duration was 16 weeks.
Period Title: Overall Study
Started 141 145 108 108
Completed 120 124 92 96
Not Completed 21 21 16 12
Reason Not Completed
Adverse Event             8             6             2             2
Lost to Follow-up             4             5             4             1
Physician Decision             1             1             0             0
Withdrawal by Subject             7             7             3             5
Required restricted medication             0             0             1             0
Met discontinuation criteria             1             0             1             1
Not specified             0             2             5             3
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin Pre-diabetic Group: Placebo Pre-diabetic Group: Colesevelam Total
Hide Arm/Group Description This group received 6 matching colesevalm placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. This treatment duration was 16 weeks. This group received 6 colevevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. This treatment duration was 16 weeks. This group received 6 colesevelam matching placebo tablets once per day for 16 weeks This group received 6 colesevelam tablets, 625mg, once per day for 16 weeks. Total of all reporting groups
Overall Number of Baseline Participants 141 145 108 108 502
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
53.9  (10.11) 52.7  (11.46) 55.7  (11.14) 53.3  (12.27) 53.3  (10.81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
Female
85
  60.3%
76
  52.4%
81
  75.0%
68
  63.0%
310
  61.8%
Male
56
  39.7%
69
  47.6%
27
  25.0%
40
  37.0%
192
  38.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
Asian 30 32 15 14 91
Black/African American 1 3 1 1 6
White 20 21 14 11 66
Hispanic 90 89 78 82 339
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
United States 30 30 17 16 93
Mexico 56 58 40 41 195
Colombia 25 26 36 37 124
India 30 31 15 14 90
Previously diagnosed with neither diabetes nor pre-diabetes  
Measure Type: Number
Unit of measure:  Participant
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
14 15 26 22 77
Previously diagnosed with pre-diabetes  
Measure Type: Number
Unit of measure:  Participant
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
17 21 81 85 204
Previously diagnosed with type 2 diabetes  
Measure Type: Number
Unit of measure:  Participant
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
110 109 1 1 221
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m squared
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
29.78  (4.44) 30.58  (4.669) 30.82  (4.18) 30.93  (4.89) 30.19  (4.57)
Fasting glucose  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
145.7  (37.54) 153.4  (39.04) 106.8  (14.80) 104.1  (11.33) 149.6  (38.43)
Fasting insulin  
Mean (Standard Deviation)
Unit of measure:  uIU/mL
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
12.82  (8.44) 13.86  (15.75) 11.03  (5.55) 13.12  (8.75) 13.34  (12.66)
Glucose 2 hours after meal  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
220.3  (58.68) 234.7  (71.36) 153.7  (39.81) 153.7  (37.90) 227.7  (65.74)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
160.6  (10.64) 162.3  (9.67) 159.1  (9.95) 160.8  (9.96) 161.5  (10.18)
Hemoglobin A1c  
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
7.53  (0.94) 7.76  (1.04) 6.07  (0.45) 6.02  (0.46) 7.65  (1.0)
Low Density Lipoprotein Cholesterol  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
135.5  (26.66) 129.1  (23.08) 136.8  (28.48) 132.8  (23.88) 132.2  (25.07)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 141 participants 145 participants 108 participants 108 participants 502 participants
77.26  (16.17) 80.84  (15.53) 78.18  (13.76) 80.63  (18.02) 79.08  (15.92)
1.Primary Outcome
Title Percent Change of Hemoglobin A1C (HbA1C) From Baseline to 16 Weeks When Given as Initial Therapy to Drug-naïve, Diabetic Subjects.
Hide Description [Not Specified]
Time Frame Baseline to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed equals the full analysis set. The full analysis set included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. This analysis set was used for the summary and analysis of all efficacy variables. LOCF was used.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks.
Overall Number of Participants Analyzed 137 138
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of change of hemoglobin A1C
-0.83  (0.064) -1.09  (0.064)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0035
Comments P-Value is for the LS mean difference between the treatment groups
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.44 to -0.09
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) in Pre-Diabetic Subjects From Baseline to 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed=the full analysis set (FAS). The FAS included randomized subjects who took at least 1 dose of randomized medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Last Observation Carried Forward was used for 16 week analyses.
Arm/Group Title Pre-Diabetes Group: Placebo Pre-Diabetes Group: Colesevelam
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks.
Overall Number of Participants Analyzed 104 103
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of change in LDL-C
1.70  (2.054) -13.89  (2.088)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pre-Diabetes Group: Placebo, Pre-Diabetes Group: Colesevelam
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -15.59
Confidence Interval (2-Sided) 95%
-21.07 to -10.11
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change in Hemoglobin A1C (HbA1C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12 and 16 Weeks.
Hide Description [Not Specified]
Time Frame Baseline to 4, 8, 12, and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed equals the full analysis set. The full analysis set included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. This analysis set was used for the summary and analysis of all efficacy variables. LOCF was not used.
Arm/Group Title Type 2 Diabetes Group:Placebo+Metformin Type 2 Diabetes Group:Colesevelam+Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 128 129
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of change in HbA1c
Baseline to 4 weeks:Pla+Met, N=128, Col+Met N=129 -0.38  (0.044) -0.53  (0.044)
Baseline to 8 weeks:Pla+Met, N=123, Col+Met N=125 -0.67  (0.055) -0.84  (0.055)
Baseline to 12 weeks:Pla+Met, N=115, Col+Met N=123 -0.86  (0.062) -1.05  (0.059)
Baseline to 16 weeks:Pla+Met, N=118, Col+Met N=122 -0.92  (0.064) -1.17  (0.063)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 4 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0123
Comments P-Value is for the LS mean difference between treatment groups
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.27 to -0.03
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 8 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0201
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.33 to -0.03
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 12 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0239
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.36 to -0.03
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 16 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0046
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.42 to -0.08
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Fasting Plasma Glucose When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 4, 8, 12, and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo+Metformin Type 2 Diabetes Group:Colesevelam+Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 130 131
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
baseline to 4 weeks Pla+Met N=130, Col+Met N=131 -19.0  (2.31) -24.0  (2.30)
baseline to 8 weeks:Pla+Met N=122, Col+Met N=126 -24.3  (1.97) -27.6  (1.94)
baseline to 12 weeks:Pla+Met N=121, Col+Met N=125 -27.3  (2.21) -28.4  (2.18)
baseline to 16 weeks:Pla+Met N=119, Col+Met N=124 -28.0  (2.21) -30.5  (2.16)
baseline to 16wks LOCF:Pla+Met N=137,Col+Met N=138 -25.9  (2.19) -28.0  (2.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 4 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1112
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.1
Confidence Interval (2-Sided) 95%
-11.3 to 1.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 8 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2167
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.3
Confidence Interval (2-Sided) 95%
-8.6 to 2.0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 12 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7269
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-7.0 to 4.9
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 16 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4063
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-8.4 to 3.4
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 16 weeks (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4909
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-8.0 to 3.9
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Fasting Insulin When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 4, 8, 12, and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group:Placebo+Metformin Type 2 Diabetes Group:Colesevelam+Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 127 127
Least Squares Mean (Standard Error)
Unit of Measure: uIU/mL
Baseline to 4 weeks:Pla+Met, N=127, Col+Met N=127 -2.124  (0.7219) -2.427  (0.7219)
Baseline to 8 weeks:Pla+Met, N=124, Col+Met N=126 -1.992  (0.5407) -3.007  (0.5376)
Baseline to 12 weeks:Pla+Met, N=117, Col+Met N=123 -2.204  (0.5159) -3.708  (0.5048)
Baseline to 16 weeks:Pla+Met, N=119, Col+Met N=124 -2.978  (0.7379) -2.802  (0.7217)
Baseline to16wks LOCF:Pla+Met,N=137,Col+Met N=138 -2.847  (0.6655) -2.637  (0.6644)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 4 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7606
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.303
Confidence Interval (2-Sided) 95%
-2.259 to 1.653
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 8 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1782
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.015
Confidence Interval (2-Sided) 95%
-2.477 to 0.447
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 12 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0332
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.504
Confidence Interval (2-Sided) 95%
-2.887 to -0.121
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 16 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8610
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.176
Confidence Interval (2-Sided) 95%
-1.805 to 2.158
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin
Comments Baseline to 16 weeks (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8196
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.210
Confidence Interval (2-Sided) 95%
-1.599 to 2.019
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Fasting C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed = the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Results are presented for both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 120 124
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
Baseline to 16 Weeks -0.295  (0.0695) -0.449  (0.0683)
Baseline to 16Wks LOCF Pla+Met N=133,Col+Met N=134 -0.284  (0.0650) -0.426  (0.0644)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1078
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.153
Confidence Interval (2-Sided) 95%
-0.340 to 0.034
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 weeks (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1146
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.141
Confidence Interval (2-Sided) 95%
-0.317 to 0.035
Estimation Comments [Not Specified]
7.Secondary Outcome
Title 30 Minute Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed = the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Results are presented for both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks.
Overall Number of Participants Analyzed 120 123
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Baseline to 16 weeks -33.1  (3.46) -33.1  (3.43)
Baseline to 16Wks LOCF Pla+Met N=133,Col+Met N=132 -29.4  (3.44) -30.4  (3.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9933
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-9.3 to 9.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8203
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-10.5 to 8.3
Estimation Comments [Not Specified]
8.Secondary Outcome
Title 1 Hour Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed = the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Results are presented for both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks.
Overall Number of Participants Analyzed 118 120
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Baseline to 16 Weeks -35.0  (3.91) -41.9  (3.88)
Baseline to 16 Weeks LOCF:N=131 Pla; N=129 Colesev -31.4  (3.92) -39.1  (3.94)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1950
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.0
Confidence Interval (2-Sided) 95%
-17.5 to 3.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1583
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.7
Confidence Interval (2-Sided) 95%
-18.3 to 3.0
Estimation Comments [Not Specified]
9.Secondary Outcome
Title 2 Hour Post-Meal Glucose Levels to in Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed = the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Results are presented for both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks.
Overall Number of Participants Analyzed 115 120
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Baseline to 16 Weeks -33.0  (4.11) -38.14  (4.02)
Baseline to 16 Weeks LOCF: Pla N=129, Met N=127 -29.4  (4.18) -36.2  (4.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3663
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.1
Confidence Interval (2-Sided) 95%
-16.1 to 6.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2524
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.6
Confidence Interval (2-Sided) 95%
-17.9 to 4.7
Estimation Comments [Not Specified]
10.Secondary Outcome
Title 2 Hour Post-Meal Insulin Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed = the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Results are presented for both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 116 118
Least Squares Mean (Standard Error)
Unit of Measure: uIU/mL
Baseline to 16 Weeks -11.601  (3.2794) -10.551  (3.2370)
Baseline to 16 Weeks LOCF: Pla N=129, Met N=127 -8.592  (3.4395) -10.156  (3.4399)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8158
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.051
Confidence Interval (2-Sided) 95%
-7.828 to 9.929
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7433
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.565
Confidence Interval (2-Sided) 95%
-10.966 to 7.836
Estimation Comments [Not Specified]
11.Secondary Outcome
Title 2 Hour Post-Meal C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed = the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Results are presented for both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks.
Overall Number of Participants Analyzed 117 121
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
Baseline to 16 Weeks -0.317  (0.2424) -0.102  (0.2373)
Baseline to 16 Weeks LOCF: Pla N=129, Met N=130 -0.205  (0.2406) -0.135  (0.2374)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5161
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.215
Confidence Interval (2-Sided) 95%
-0.437 to 0.867
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8319
Comments P-Value is for the LS Mean Difference between treatment groups.
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.070
Confidence Interval (2-Sided) 95%
-0.581 to 0.722
Estimation Comments [Not Specified]
12.Secondary Outcome
Title The Percent Change of Low Density Lipoprotein Cholesterol (LDL-C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 8, and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam+Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 122 124
Least Squares Mean (Standard Error)
Unit of Measure: percentage of change in LDL-C
Baseline to 8 Weeks -5.83  (1.631) -24.01  (1.614)
Baseline to 16 Weeks: Pla N=119, Met N=124 -4.94  (1.852) -22.02  (1.813)
Baseline to 16 Weeks LOCF: Pla N=137, Met N=136 -5.11  (1.695) -21.44  (1.700)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam+Metformin
Comments Baseline to 8 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -18.19
Confidence Interval (2-Sided) 95%
-22.61 to -13.76
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam+Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -17.08
Confidence Interval (2-Sided) 95%
-22.09 to -12.08
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam+Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -16.33
Confidence Interval (2-Sided) 95%
-20.96 to -11.69
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Percent Change of Non-High Density Lipoprotein (Non-HDL) Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 8, and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 122 125
Least Squares Mean (Standard Error)
Unit of Measure: percentage of change in non-HDL
Baseline to 8 Weeks -5.79  (1.327) -18.19  (1.316)
Baseline to 16 Weeks: Pla N=119, Met N=124 -5.08  (1.460) -14.36  (1.436)
Baseline to 16 Weeks LOCF: Pla N=137, Met N=136 -5.38  (1.338) -13.70  (1.346)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 8 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -12.40
Confidence Interval (2-Sided) 95%
-15.99 to -8.81
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -9.28
Confidence Interval (2-Sided) 95%
-13.23 to -5.34
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Week LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.33
Confidence Interval (2-Sided) 95%
-11.98 to -4.67
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Percent Change of High Density Lipoprotein Cholesterol(HDL-C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 8, and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 122 125
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of change
Baseline to 8 Weeks 2.98  (1.506) 5.61  (1.488)
Baseline to 16 Weeks: Pla N=119, Met N=124 7.46  (1.277) 8.78  (1.250)
Baseline to 16 Weeks LOCF: Pla N=137, Met N=136 6.58  (1.160) 8.39  (1.165)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 8 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2026
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 2.63
Confidence Interval (2-Sided) 95%
-1.43 to 6.70
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4506
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.32
Confidence Interval (2-Sided) 95%
-2.12 to 4.75
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2609
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.81
Confidence Interval (2-Sided) 95%
-1.35 to 4.97
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Percent Change of Total Cholesterol (TC) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 8, and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 122 125
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of change of TC
Baseline to 8 Weeks -4.46  (1.009) -13.26  (1.000)
Baseline to 16 Weeks: Pla N=119, Met=124 -2.85  (1.217) -9.79  (1.197)
Baseline to 16 Weeks LOCF: Pla N=137, Met=136 -3.22  (1.115) -9.31  (1.121)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 8 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.81
Confidence Interval (2-Sided) 95%
-11.53 to -6.08
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.94
Confidence Interval (2-Sided) 95%
-10.23 to -3.66
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.09
Confidence Interval (2-Sided) 95%
-9.14 to -3.05
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Percent Change of Triglycerides (TG)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 8, and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 122 125
Median (Inter-Quartile Range)
Unit of Measure: Percentage of change of TG
Baseline to 8 Weeks
-7.39
(-11.41 to 0.58)
1.28
(-4.48 to 5.58)
Baseline to 16 Weeks: Pla N=119, Met N=124
-7.12
(-25.58 to 7.32)
8.63
(-8.74 to 36.85)
Baseline to 16 Weeks LOCF: Pla N=137, Met N=136
-9.55
(-24.13 to 14.40)
8.80
(6.25 to 15.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 8 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0171
Comments The P-Value was from the non-parametric ANCOVA stratified by country.
Method ANCOVA
Comments The median difference was calculated using Hodges-Lehmann point estimate and corresponding 95% CI was constructed using the method of Moses.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.05
Confidence Interval (2-Sided) 95%
-0.33 to 13.99
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The P-Value was from the non-parametric ANCOVA stratified by country.
Method ANCOVA
Comments The median difference was calculated using Hodges-Lehmann point estimate and corresponding 95% CI was constructed using the method of Moses.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 17.71
Confidence Interval (2-Sided) 95%
9.66 to 25.54
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The P-Value was from the non-parametric ANCOVA stratified by country.
Method ANCOVA
Comments The median difference was calculated using Hodges-Lehmann point estimate and corresponding 95% CI was constructed using the method of Moses.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 18.62
Confidence Interval (2-Sided) 95%
11.18 to 25.74
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Percent Change of Apolipoprotein A-1 (Apo A-1) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 8, and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 118 124
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of change in Apo A-1
Baseline to 8 Weeks 3.30  (1.047) 6.12  (1.027)
Baseline to 16 Weeks: Pla N=113, Met N=120 4.86  (1.052) 8.51  (1.024)
Baseline to 16 Weeks LOCF: Pla N=133, Met N=134 4.02  (0.957) 8.45  (0.953)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 8 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0496
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.81
Confidence Interval (2-Sided) 95%
0.0 to 5.62
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0117
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.65
Confidence Interval (2-Sided) 95%
0.82 to 6.47
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.43
Confidence Interval (2-Sided) 95%
1.83 to 7.03
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Percent Change of Apolipoprotein B (Apo B)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 8, and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 118 124
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of change in Apo B
Baseline to 8 Weeks -4.59  (1.184) 16.15  (1.158)
Baseline to 16 Weeks: Pla N=113, Met N=120 -3.89  (1.340) -13.42  (1.307)
Baseline to 16 Weeks LOCF: Pla N=133, Met N=134 -4.20  (1.242) -12.17  (1.239)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 8 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -11.56
Confidence Interval (2-Sided) 95%
-14.74 to -8.38
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -9.53
Confidence Interval (2-Sided) 95%
-13.14 to -5.92
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.97
Confidence Interval (2-Sided) 95%
-11.35 to -4.59
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Percent Change of Apolipoprotein C3 (Apo C3)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 8, and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 122 125
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of change in Apo C3
Baseline to 8 Weeks 0.01  (2.527) 12.58  (2.495)
Baseline to 16 Weeks: Pla N=117, Met N=120 4.06  (2.932) 18.58  (2.871)
Baseline to 16 Weeks LOCF: Pla N=136, N=136 2.82  (2.621) 17.89  (2.620)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 8 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 12.57
Confidence Interval (2-Sided) 95%
5.76 to 19.38
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 14.52
Confidence Interval (2-Sided) 95%
6.64 to 22.40
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 15.08
Confidence Interval (2-Sided) 95%
7.95 to 22.20
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Change in the Levels of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF) Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks.
Overall Number of Participants Analyzed 119 119 133 129
Least Squares Mean (Standard Error)
Unit of Measure: nmol/L
Total Very Low Density Lipoprotein (VLDL) Particle -4.03  (2.361) 2.81  (2.355) -3.71  (2.167) 2.68  (2.188)
VLDL Chylomicron Particles -0.58  (0.554) 1.73  (0.552) -0.58  (0.507) 1.76  (0.511)
Medium VLDL Particles -2.31  (1.496) 4.84  (1.492) -2.28  (1.383) 4.85  (1.396)
Small VLDL Particles -1.12  (1.536) -4.00  (1.532) -0.83  (1.413) -4.06  (1.426)
Total Low Density Lipoprotein (LDL) Particles -104.0  (27.04) -303.3  (27.05) -109.5  (25.49) -295.5  (25.77)
Intermediate Density Lipoprotein Particles -9.6  (4.24) -21.3  (4.24) -8.9  (4.03) -19.6  (4.08)
Large LDL Particles 52.1  (15.74) -25.5  (15.69) 45.1  (14.60) -24.2  (14.73)
Small LDL Particles -146.9  (31.63) -256.7  (31.63) -145.9  (29.52) -252.7  (29.84)
Medium Small LDL Particles -32.0  (7.16) -48.2  (7.15) -30.8  (6.72) -46.2  (6.78)
Very Small LDL Particles -115.0  (24.96) -208.7  (24.97) -115.3  (23.31) -206.6  (23.57)
Total High Density Lipoprotein (HDL) Particles 1.47  (0.352) 2.41  (0.351) 1.34  (0.332) 2.35  (0.335)
Large HDL Particles 0.64  (0.160) 1.09  (0.161) 0.55  (0.153) 1.00  (0.155)
Medium HDL Particles -0.19  (0.275) 0.50  (0.274) -0.26  (0.259) 0.59  (0.261)
Small HDL Particles 1.04  (0.385) 0.74  (0.384) 1.05  (0.362) 0.70  (0.366)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Total Very Low Density Lipoprotein (VLDL) Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0363
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.84
Confidence Interval (2-Sided) 95%
0.44 to 13.24
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Total Very Low Density Lipoprotein (VLDL) Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0347
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.39
Confidence Interval (2-Sided) 95%
0.46 to 12.31
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments VLDL Chylomicron Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0028
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.31
Confidence Interval (2-Sided) 95%
0.80 to 3.81
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments VLDL Chylomicron Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.34
Confidence Interval (2-Sided) 95%
0.96 to 3.73
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Medium VLDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.13
Confidence Interval (2-Sided) 95%
3.10 to 11.21
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Medium VLDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.13
Confidence Interval (2-Sided) 95%
3.35 to 10.91
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Small VLDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1750
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.88
Confidence Interval (2-Sided) 95%
-7.04 to 1.29
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Small VLDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1007
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.23
Confidence Interval (2-Sided) 95%
-7.10 to 0.63
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Total Low Density Lipoprotein (LDL) Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -199.3
Confidence Interval (2-Sided) 95%
-272.9 to -125.8
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Total Low Density Lipoprotein (LDL) Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -186.1
Confidence Interval (2-Sided) 95%
-255.9 to -116.3
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Intermediate Density Lipoprotein Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0466
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -11.7
Confidence Interval (2-Sided) 95%
-23.3 to -0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Intermediate Density Lipoprotein Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0570
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -10.7
Confidence Interval (2-Sided) 95%
-21.8 to 0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Large LDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -77.7
Confidence Interval (2-Sided) 95%
-120.3 to -35.0
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Large LDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -69.3
Confidence Interval (2-Sided) 95%
-109.2 to -29.3
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Small LDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0124
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -109.9
Confidence Interval (2-Sided) 95%
-195.8 to -23.9
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Small LDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0098
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -106.8
Confidence Interval (2-Sided) 95%
-187.6 to -26.0
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Medium Small LDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1020
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -16.2
Confidence Interval (2-Sided) 95%
-35.6 to 3.2
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Medium Small LDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0997
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -15.4
Confidence Interval (2-Sided) 95%
-33.8 to 3.0
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Very Small LDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0069
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -93.7
Confidence Interval (2-Sided) 95%
-161.6 to -25.9
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Very Small LDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0052
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -91.4
Confidence Interval (2-Sided) 95%
-155.2 to -27.5
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Total High Density Lipoprotein (HDL) Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0524
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
-0.01 to 1.90
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Total High Density Lipoprotein (HDL) Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0301
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.10 to 1.91
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Large HDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0416
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.02 to 0.89
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Large HDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0333
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.04 to 0.88
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Medium HDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0693
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
-0.05 to 1.44
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Medium HDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0187
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.14 to 1.56
Estimation Comments [Not Specified]
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Small HDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5765
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-1.34 to 0.75
Estimation Comments [Not Specified]
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Small HDL Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4762
Comments P-Value is for the LS Mean Difference between treatment group
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-1.35 to 0.63
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change in the Size of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF) Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks.
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks.
Overall Number of Participants Analyzed 119 119 133 129
Least Squares Mean (Standard Error)
Unit of Measure: nm
Very Low Density Lipoprotein Particles -0.80  (0.868) 1.41  (0.866) -1.02  (0.796) 1.73  (0.804)
Low Density Lipoprotein Particles 0.20  (0.053) 0.15  (0.053) 0.19  (0.049) 0.15  (0.050)
High Density Lipoprotein Particles 0.08  (0.023) 0.17  (0.023) 0.08  (0.021) 0.17  (0.022)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Very Low Density Lipoprotein Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0652
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.21
Confidence Interval (2-Sided) 95%
-0.14 to 4.57
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Very Low Density Lipoprotein Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0137
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.74
Confidence Interval (2-Sided) 95%
0.57 to 4.92
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments Low Density Lipoprotien Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4726
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.20 to 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments Low Density Lipoprotein Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5715
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.17 to 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks, Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks
Comments High Density Lipoprotein Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0083
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
0.02 to 0.15
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF)
Comments High Density Lipoprotein Particles
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0022
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
0.03 to 0.15
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Change in the Calculated Total Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Hide Description [Not Specified]
Time Frame Baseline to 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks.
Overall Number of Participants Analyzed 119 119
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Baseline to 16 Weeks -8.5  (6.44) 17.6  (6.43)
Baseline to 16 Weeks LOCF: Pla N=133, Met N=129 -9.0  (5.88) 18.2  (5.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0036
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 26.0
Confidence Interval (2-Sided) 95%
8.6 to 43.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 27.2
Confidence Interval (2-Sided) 95%
11.2 to 43.3
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Change in the Calculated Very Low Density Lipoprotein Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Hide Description These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary.
Time Frame Baseline to 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks.
Overall Number of Participants Analyzed 119 119
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Baseline to 16 Weeks -7.4  (6.36) 22.4  (6.34)
Baseline to 16 Weeks LOCF: Pla N=133, Met N= 129 -7.9  (5.81) 22.9  (5.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 29.8
Confidence Interval (2-Sided) 95%
12.5 to 47.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 30.7
Confidence Interval (2-Sided) 95%
14.9 to 46.6
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Change in the Calculated High Density Lipoprotein Cholesterol When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Hide Description These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary.
Time Frame Baseline to 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF.
Arm/Group Title Type 2 Diabetes Group: Placebo + Metformin Type 2 Diabetes Group: Colesevelam + Metformin
Hide Arm/Group Description:
This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks.
This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks.
Overall Number of Participants Analyzed 119 119
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Baseline to 16 Weeks 3.2  (0.62) 5.8  (0.62)
Baseline to 16 Weeks LOCF: Pla N=133, Met N=129 2.9  (0.59) 5.6  (0.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0033
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.6
Confidence Interval (2-Sided) 95%
0.9 to 4.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Type 2 Diabetes Group: Placebo + Metformin, Type 2 Diabetes Group: Colesevelam + Metformin
Comments Baseline to 16 Weeks LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments P-Value is for the LS Mean Difference between treatment groups
Method ANCOVA
Comments