Trial Outcomes & Findings for Colesevelam as Add-on to Pioglitazone Therapy for Type 2 Diabetes Mellitus (NCT NCT00789750)

NCT ID: NCT00789750

Last Updated: 2017-06-26

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 562 participants
• Primary outcome timeframe: Baseline, Week 24
• Results posted on: 2017-06-26

Participant Flow

The safety set includes all randomized participants who took at least one dose of study medication and have at least one post-baseline safety measurement. The intent-to-treat set includes all randomized subjects who took at least one dose of study medication, and had a baseline and at least one post-baseline HbA1c or FPG measurement.

There was a lead-in period that occurred after participant enrollment, but before randomization.1538 were screened, and a total of 562 participants were randomized.

Participant milestones

Measure	Colesevelam Colesevelam tablets with pioglitazone therapy	Placebo Placebo tablets with pioglitazone therapy
Overall Study STARTED	280	282
Overall Study Dropped During run-in Period	6	5
Overall Study Safety Set	274	277
Overall Study Intent to Treat Set	271	276
Overall Study COMPLETED	221	222
Overall Study NOT COMPLETED	59	60

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Colesevelam as Add-on to Pioglitazone Therapy for Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Measure	Colesevelam n=280 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=282 Participants Placebo tablets with pioglitazone therapy	Total n=562 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	220 Participants n=93 Participants	222 Participants n=4 Participants	442 Participants n=27 Participants
Age, Categorical >=65 years	60 Participants n=93 Participants	60 Participants n=4 Participants	120 Participants n=27 Participants
Age, Continuous	56.3 years STANDARD_DEVIATION 10.22 • n=93 Participants	55.6 years STANDARD_DEVIATION 10.61 • n=4 Participants	56.0 years STANDARD_DEVIATION 10.41 • n=27 Participants
Sex: Female, Male Female	136 Participants n=93 Participants	106 Participants n=4 Participants	242 Participants n=27 Participants
Sex: Female, Male Male	144 Participants n=93 Participants	176 Participants n=4 Participants	320 Participants n=27 Participants
Race/Ethnicity, Customized Caucasian	179 Participants n=93 Participants	172 Participants n=4 Participants	351 Participants n=27 Participants
Race/Ethnicity, Customized Black	59 Participants n=93 Participants	56 Participants n=4 Participants	115 Participants n=27 Participants
Race/Ethnicity, Customized Asian	23 Participants n=93 Participants	30 Participants n=4 Participants	53 Participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	16 Participants n=93 Participants	21 Participants n=4 Participants	37 Participants n=27 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Other	3 Participants n=93 Participants	2 Participants n=4 Participants	5 Participants n=27 Participants
Region of Enrollment United States	280 participants n=93 Participants	282 participants n=4 Participants	562 participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat, last observation carried forward

Outcome measures

Measure	Colesevelam n=271 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=276 Participants Placebo tablets with pioglitazone therapy
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24	-0.34 percent Standard Error 0.083	-0.02 percent Standard Error 0.083

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Intent to treat set, with baseline and post-baseline measures at the given time point

Outcome measures

Measure	Colesevelam n=264 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=266 Participants Placebo tablets with pioglitazone therapy
Change From Baseline in HbA1c at Week 4	-0.28 percent Standard Error 0.037	-0.11 percent Standard Error 0.037

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: Intent to treat set, with baseline and post-baseline measures at the given time point

Outcome measures

Measure	Colesevelam n=256 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=256 Participants Placebo tablets with pioglitazone therapy
Change From Baseline in HbA1c at Week 8	-0.35 percent Standard Error 0.055	-0.14 percent Standard Error 0.056

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Intent to treat set, with baseline and post-baseline measures at the given time point

Outcome measures

Measure	Colesevelam n=232 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=232 Participants Placebo tablets with pioglitazone therapy
Change From Baseline in HbA1c at Week 16	-0.50 percent Standard Error 0.078	-0.15 percent Standard Error 0.078

SECONDARY outcome

Timeframe: Week 24

Population: Intent-to-treat set, with last observation carried forward

Outcome measures

Measure	Colesevelam n=271 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=276 Participants Placebo tablets with pioglitazone therapy
Number of Participants Achieving an HbA1c Goal of <7.0%	56 Participants	35 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants in the intent-to-treat set with values at both baseline and Week 24 with last observation carried forward

In this study a reduction in FPG of at least 30 mg/dL is considered glycemic response.

Outcome measures

Measure	Colesevelam n=268 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=270 Participants Placebo tablets with pioglitazone therapy
Change From Baseline in Fasting Plasma Glucose (FPG)	-4.8 mg/dL Standard Error 3.66	9.9 mg/dL Standard Error 3.66

SECONDARY outcome

Timeframe: Week 24

Population: Intent-to-treat set, with last count carried forward

Outcome measures

Measure	Colesevelam n=271 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=276 Participants Placebo tablets with pioglitazone therapy
Number of Participants With a Decrease of >= 0.7 Percent in HbA1c	108 Participants	70 Participants

SECONDARY outcome

Timeframe: Week 24

Population: Intent-to-treat set, with last count carried forward

Outcome measures

Measure	Colesevelam n=271 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=276 Participants Placebo tablets with pioglitazone therapy
Number of Participants With a Decrease of >= 0.5 Percent in HbA1c	147 Participants	106 Participants

SECONDARY outcome

Timeframe: Week 24

Population: Intent-to-treat set, with last count carried forward

Outcome measures

Measure	Colesevelam n=271 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=276 Participants Placebo tablets with pioglitazone therapy
Number of Participants With a Reduction in FPG of >= 30 mg/dL	60 Participants	47 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat set, with values at both baseline and Week 24 with last observation carried forward

TC is measured in milligrams per deciliter (mg/dL)

Outcome measures

Measure	Colesevelam n=263 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=263 Participants Placebo tablets with pioglitazone therapy
Percent Change From Baseline in Total Cholesterol (TC)	-3.4 percentage of change Standard Error 1.33	3.1 percentage of change Standard Error 1.32

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat set, with values at both baseline and Week 24 with last count carried forward

LDL-C is measured in mg/dL

Outcome measures

Measure	Colesevelam n=262 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=263 Participants Placebo tablets with pioglitazone therapy
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)	-9.1 percentage of change Standard Error 2.14	7.3 percentage of change Standard Error 2.12

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat set, with values at both baseline and Week 24 with last observation carried forward

HDL-C is measured in mg/dL

Outcome measures

Measure	Colesevelam n=263 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=263 Participants Placebo tablets with pioglitazone therapy
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)	2.9 percentage of change Standard Error 1.30	1.1 percentage of change Standard Error 1.30

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat set, with values at both baseline and Week 24 with last observation carried forward

Non-HDL-C is measured in mg/dL

Outcome measures

Measure	Colesevelam n=263 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=263 Participants Placebo tablets with pioglitazone therapy
Percent Change From Baseline in Non-HDL-C	-5.2 percentage of change Standard Error 1.85	4.6 percentage of change Standard Error 1.84

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat set, with values at both baseline and Week 24 with last observation carried forward

TG are measured in mg/dL

Outcome measures

Measure	Colesevelam n=263 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=263 Participants Placebo tablets with pioglitazone therapy
Percent Change From Baseline in Triglycerides (TG)	14.1 percentage of change Interval -4.32 to 32.52	2.2 percentage of change Interval -14.6 to 19.0

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat, with values at both baseline and Week 24 with last observation carried forward

Apo A-1 is measured in mg/dL

Outcome measures

Measure	Colesevelam n=263 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=262 Participants Placebo tablets with pioglitazone therapy
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-I)	3.2 percentage of change Standard Error 0.92	-0.2 percentage of change Standard Error 0.92

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat set, with values at both baseline and Week 24 with last observation carried forward

Apo B is measured in mg/dL

Outcome measures

Measure	Colesevelam n=263 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=262 Participants Placebo tablets with pioglitazone therapy
Percent Change From Baseline in Apolipoprotein B (Apo B)	-5.2 percentage of change Standard Error 1.51	3.6 percentage of change Standard Error 1.51

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat set, with values at both baseline and Week 24 with last observation carried forward

Outcome measures

Measure	Colesevelam n=246 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=248 Participants Placebo tablets with pioglitazone therapy
Change From Baseline in Fasting Insulin Levels	0.2 µIU/mL Standard Error 1.76	0.8 µIU/mL Standard Error 1.76

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat set, with values at both baseline and Week 24 with last observation carried forward

Outcome measures

Measure	Colesevelam n=253 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=255 Participants Placebo tablets with pioglitazone therapy
Change From Baseline in Fasting C-peptide	0.1 ng/mL Standard Error 0.10	0.3 ng/mL Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat set, with values at both baseline and Week 24 with last observation carried forward

HOMA-IR is a calculation of fasting insulin and fasting glucose that shows the level of insulin resistance. Lower numbers are better.

Outcome measures

Measure	Colesevelam n=227 Participants Colesevelam tablets with pioglitazone therapy	Placebo n=227 Participants Placebo tablets with pioglitazone therapy
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	0.2 calculation Standard Error 0.71	0.3 calculation Standard Error 0.72

Adverse Events

Colesevelam

Serious events: 11 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Colesevelam n=274 participants at risk Colesevelam tablets with pioglitazone therapy	Placebo n=277 participants at risk Placebo tablets with pioglitazone therapy
Blood and lymphatic system disorders Leukopenia	0.00% 0/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.36% 1/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Gastrointestinal disorders Inguinal hernia	0.36% 1/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.00% 0/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
General disorders Non-cardiac chest pain	0.73% 2/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.36% 1/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Infections and infestations Diabetic foot infection	0.36% 1/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.00% 0/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Infections and infestations Gastroenteritis	0.00% 0/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.36% 1/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Infections and infestations Osteomyelitis	0.36% 1/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.00% 0/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Infections and infestations Pneumonia	0.00% 0/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.36% 1/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Infections and infestations Urinary tract infection	0.36% 1/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.00% 0/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Metabolism and nutrition disorders Dehydration	0.00% 0/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.72% 2/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung squamous cell carcinoma stage unspecified	0.36% 1/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.00% 0/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.36% 1/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.00% 0/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Nervous system disorders Cerebrovascular accident	0.36% 1/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.00% 0/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Nervous system disorders Presyncope	0.36% 1/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.00% 0/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Nervous system disorders Syncope	0.36% 1/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.00% 0/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Psychiatric disorders Bipolar disorder	0.36% 1/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.00% 0/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.
Vascular disorders Hypertension	0.36% 1/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	0.00% 0/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.

Other adverse events

Measure	Colesevelam n=274 participants at risk Colesevelam tablets with pioglitazone therapy	Placebo n=277 participants at risk Placebo tablets with pioglitazone therapy
Metabolism and nutrition disorders Hypoglycaemia	4.0% 11/274 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.	6.1% 17/277 • Adverse events that first occurred or worsened in severity after initiation of treatment with the investigational product and up to the end of study assessment and follow-up period, within 3 years, 3 months Four potential cardiac events were referred to the Clinical Event Committee (CEC) for adjudication: 1 event was adjudicated as stroke and was considered unrelated to study treatment, while 3 were adjudicated as noncardiac chest pain. No serious adverse events in either treatment group were considered drug-related.

Additional Information

Global Clinical Leader

Daiichi Sankyo, Inc.

Phone: 9089926400

Results disclosure agreements

• Principal investigator is a sponsor employee PI agrees to wait until after coordinated multicenter publication or one year after the trial is over, whichever occurs first. After such time, Study Site will submit any publication to DSI for CCI review and comment at least forty-five (45) days prior to submission. Site agrees to delay publication for an additional sixty (60) days for legal (e.g., patent) concerns. Nothing shall be taken as giving DSI any right of editorial control over any publication prepared by Study Site.
• Publication restrictions are in place

Restriction type: OTHER