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.

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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

Reporting Groups

	Description
Type 2 Diabetes Group: Placebo + Metformin	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.
Type 2 Diabetes Group: Colesevelam + Metformin	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.
Pre-diabetic Group: Placebo	This group was given 6 placebo tablets once a day. They matched the colesevelam tablets. This treatment duration was 16 weeks.
Pre-diabetic Group: Colesevelam	This group was given 6 colesevelam tablets, 625mg, once a day. This treatment duration was 16 weeks.

Participant Flow:   Overall Study

	Type 2 Diabetes Group: Placebo + Metformin	Type 2 Diabetes Group: Colesevelam + Metformin	Pre-diabetic Group: Placebo	Pre-diabetic Group: Colesevelam
STARTED	141	145	108	108
COMPLETED	120	124	92	96
NOT COMPLETED	21	21	16	12
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

Reporting Groups

	Description
Type 2 Diabetes Group: Placebo + Metformin	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.
Type 2 Diabetes Group: Colesevelam + Metformin	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.
Pre-diabetic Group: Placebo	This group received 6 colesevelam matching placebo tablets once per day for 16 weeks
Pre-diabetic Group: Colesevelam	This group received 6 colesevelam tablets, 625mg, once per day for 16 weeks.
Total	Total of all reporting groups

Baseline Measures

	Type 2 Diabetes Group: Placebo + Metformin	Type 2 Diabetes Group: Colesevelam + Metformin	Pre-diabetic Group: Placebo	Pre-diabetic Group: Colesevelam	Total
Number of Participants   [units: participants]	141	145	108	108	502
Age   [units: years] Mean ± Standard Deviation	53.9  ± 10.11	52.7  ± 11.46	55.7  ± 11.14	53.3  ± 12.27	53.3  ± 10.81
Gender   [units: participants]
Female	85	76	81	68	310
Male	56	69	27	40	192
Race/Ethnicity, Customized   [units: 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   [units: 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   [units: Participant]	14	15	26	22	77
Previously diagnosed with pre-diabetes   [units: Participant]	17	21	81	85	204
Previously diagnosed with type 2 diabetes   [units: Participant]	110	109	1	1	221
Body Mass Index   [units: kg/m squared] Mean ± Standard Deviation	29.78  ± 4.44	30.58  ± 4.669	30.82  ± 4.18	30.93  ± 4.89	30.19  ± 4.57
Fasting glucose   [units: mg/dL] Mean ± Standard Deviation	145.7  ± 37.54	153.4  ± 39.04	106.8  ± 14.80	104.1  ± 11.33	149.6  ± 38.43
Fasting insulin   [units: uIU/mL] Mean ± Standard Deviation	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   [units: mg/dL] Mean ± Standard Deviation	220.3  ± 58.68	234.7  ± 71.36	153.7  ± 39.81	153.7  ± 37.90	227.7  ± 65.74
Height   [units: cm] Mean ± Standard Deviation	160.6  ± 10.64	162.3  ± 9.67	159.1  ± 9.95	160.8  ± 9.96	161.5  ± 10.18
Hemoglobin A1c   [units: Percent] Mean ± Standard Deviation	7.53  ± 0.94	7.76  ± 1.04	6.07  ± 0.45	6.02  ± 0.46	7.65  ± 1.0
Low Density Lipoprotein Cholesterol   [units: mg/dL] Mean ± Standard Deviation	135.5  ± 26.66	129.1  ± 23.08	136.8  ± 28.48	132.8  ± 23.88	132.2  ± 25.07
Weight   [units: kg] Mean ± Standard Deviation	77.26  ± 16.17	80.84  ± 15.53	78.18  ± 13.76	80.63  ± 18.02	79.08  ± 15.92

1.  Primary:

Percent Change of Hemoglobin A1C (HbA1C) From Baseline to 16 Weeks When Given as Initial Therapy to Drug-naïve, Diabetic Subjects.   [ Time Frame: Baseline to 16 weeks ]

2.  Primary:

Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

3.  Secondary:

Percent Change in Hemoglobin A1C (HbA1C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12 and 16 Weeks.   [ Time Frame: Baseline to 4, 8, 12, and 16 weeks ]

4.  Secondary:

Fasting Plasma Glucose When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12, and 16 weeks ]

5.  Secondary:

Fasting Insulin When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12, and 16 weeks ]

6.  Secondary:

Fasting C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

7.  Secondary:

30 Minute Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

8.  Secondary:

1 Hour Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

9.  Secondary:

2 Hour Post-Meal Glucose Levels to in Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

10.  Secondary:

2 Hour Post-Meal Insulin Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

11.  Secondary:

2 Hour Post-Meal C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

12.  Secondary:

The Percent Change of Low Density Lipoprotein Cholesterol (LDL-C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

13.  Secondary:

Percent Change of Non-High Density Lipoprotein (Non-HDL) Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

14.  Secondary:

Percent Change of High Density Lipoprotein Cholesterol(HDL-C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

15.  Secondary:

Percent Change of Total Cholesterol (TC) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

16.  Secondary:

Percent Change of Triglycerides (TG)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

17.  Secondary:

Percent Change of Apolipoprotein A-1 (Apo A-1) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

18.  Secondary:

Percent Change of Apolipoprotein B (Apo B)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

19.  Secondary:

Percent Change of Apolipoprotein C3 (Apo C3)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

20.  Secondary:

Change in the Levels of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

21.  Secondary:

Change in the Size of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

22.  Secondary:

Change in the Calculated Total Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

23.  Secondary:

Change in the Calculated Very Low Density Lipoprotein Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

24.  Secondary:

Change in the Calculated High Density Lipoprotein Cholesterol When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

25.  Secondary:

Percent of Subjects Achieving HbA1c Goal of <7.0% at Weeks 4, 8, 12, and 16 if Baseline HbA1c Was > or = to 7.0% When Given to Drug-naïve, Diabetics   [ Time Frame: Baseline to 4, 8, 12, and 16 Weeks ]

26.  Secondary:

Percent of Subject Achieving HbA1c Goal of <6.5% at Weeks 4, 8, 12, and 16 When Given to Drug-naïve, Diabetic Subjects   [ Time Frame: Baseline to 4, 8, 12 and 16 weeks ]

27.  Secondary:

Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <100 mg/dL at Weeks 8, 16 When Given to Drug-naïve, Diabetic Subjects   [ Time Frame: Baseline to Weeks 8, and 16 ]

28.  Secondary:

Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol Goal of <70 mg/dL at Weeks 8, 16 When Given as to Drug-naïve, Diabetics   [ Time Frame: Baseline to Weeks 8, and 16 ]

29.  Secondary:

Change in Body Weight When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

30.  Secondary:

Change in Waist-to-Hip Ratio When Given to Drug-Naive Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

31.  Secondary:

Change in Plasma Glucose Area Under the Curve (0 to 120 Minutes) From the Baseline Glucose Tolerance Test (GTT) to the 16 Week GTT   [ Time Frame: Baseline vs. 16 Weeks ]

32.  Secondary:

Percent Change of Various Calculated Lipid Parameters When Given as Initial Therapy to Drug-naïve, Diabetic From Baseline to 16 Weeks Subjects   [ Time Frame: Baseline to 16 Weeks ]

33.  Secondary:

Percent of Subjects Achieving 2-Hr. Post Meal Glucose Goal of <180 mg/dL When Given to Drug-naïve, Diabetic Subjects From Baseline to Week 16   [ Time Frame: Baseline to Week 16 ]

34.  Secondary:

Percent of Subjects Achieving Hs-C-Reactive Protein Goal of <2.0 mg/L When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

35.  Secondary:

Percent Change in Low Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

36.  Secondary:

Percent Change in Non-High Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

37.  Secondary:

Percent Change in High Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

38.  Secondary:

Percent Change in Total Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

39.  Secondary:

Percent Change in Apolipoprotein A-1 in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

40.  Secondary:

Percent Change in Apolipoprotein B in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

41.  Secondary:

Percent Change in Apolipoprotein CIII in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

42.  Secondary:

Percent Change in Triglycerides in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

43.  Secondary:

Percent Change in Hs-C-Reactive Protein in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline 16 Weeks ]

44.  Secondary:

Level of Various Lipoprotein Particles in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

45.  Secondary:

Particle Size of Various Lipoprotein Particles in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

46.  Secondary:

Change of Various Calculated Lipid Parameters in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

47.  Secondary:

Percent Change of HbA1c in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12, and 16 Weeks ]

48.  Secondary:

Percent Change of Fasting Plasma Glucose in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12, and 16 weeks ]

49.  Secondary:

Percent Change of Fasting Insulin in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12, and 16 Weeks ]

50.  Secondary:

Change of Fasting C-peptide Levels in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

51.  Secondary:

Change of Glucose Levels 30 Minutes Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

52.  Secondary:

Change of Glucose Levels 1 Hour Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

53.  Secondary:

Change of Glucose Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

54.  Secondary:

Change of Insulin Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

55.  Secondary:

Change of C-Peptide Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

56.  Secondary:

Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <100 mg/dL at Weeks 8, 16 in Pre-Diabetic Subjects   [ Time Frame: Baseline to 8, and 16 Weeks ]

57.  Secondary:

Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <70 mg/dL at Weeks 8, 16 in Pre-Diabetic Subjects   [ Time Frame: Baseline to 8, and 16 Weeks ]

58.  Secondary:

Change in Body Weight in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

59.  Secondary:

Change in Waist-to-Hip Ratio in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

60.  Secondary:

Area Under the Curve for Plasma Glucose From 0 to 120 Minutes During the Oral Glucose Tolerance Tests in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

61.  Secondary:

Percent Achievement of <140 mg/dL Plasma Glucose 2 Hours Post the Oral Glucose Tolerance Test in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was >or= to 140 mg/dL From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

62.  Secondary:

Percent Achievement of <110 mg/dL Fasting Plasma Glucose in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 110 mg/dL From Baseline to 4, 8, 12, and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12, and 16 Weeks ]

63.  Secondary:

Percent Achievement of <100 mg/dL Fasting Plasma Glucose in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 100 mg/dL From Baseline to 4, 8, 12 and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12 and 16 weeks ]

64.  Secondary:

Percent Achievement of <140 mg/dL Plasma Glucose Post 2 Hour Glucose Tolerance Test and Fasting Plasma Glucose <110 mg/dL in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

65.  Secondary:

Percent Achievement of Hs-C-Reactive Protein <2.0 mg/L in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 2.0 mg/L From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

66.  Secondary:

Percent of Subjects Meeting Type 2 Diabetes Criteria (Fasting Plasma Glucose >or= to 126 mg/dL or Plasma Glucose >or= to 200 mg/dL Post 2 Hr Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]