Trial Outcomes & Findings for The Effect of Welchol on Glucose Metabolism in Type 2 Diabetics (NCT NCT00951899)

NCT ID: NCT00951899

Last Updated: 2013-11-11

Results Overview

Total Disposition Index (DI) is a calculated value which represents the ability of a person's pancreas to lower blood glucose. A higher number means the pancreas is better able to lower blood glucose and a lower number means the pancreas is less able to lower blood glucose.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 38 participants
• Primary outcome timeframe: Baseline, 12 weeks
• Results posted on: 2013-11-11

Participant Flow

Participants with type 2 diabetes on monotherapy with Metformin were recruited by advertisement from 2009 to 2010 at Mayo Clinic in Rochester, Minnesota.

39 subjects provided written informed consent to participate. One subject lost intravenous access during the baseline study and withdrew consent. The remaining 38 were randomized.

Participant milestones

Measure	Colesevelam Treatment with colesevelam in addition to metformin and diet	Placebo Placebo plus diet and metformin
Overall Study STARTED	19	19
Overall Study COMPLETED	19	19
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Effect of Welchol on Glucose Metabolism in Type 2 Diabetics

Baseline characteristics by cohort

Measure	Colesevelam n=19 Participants Treatment with colesevelam in addition to metformin and diet	Placebo n=19 Participants Placebo plus diet and metformin	Total n=38 Participants Total of all reporting groups
Age Continuous	62.6 years STANDARD_DEVIATION 5.9 • n=5 Participants	60.2 years STANDARD_DEVIATION 6.3 • n=7 Participants	61 years STANDARD_DEVIATION 6.1 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	19 participants n=7 Participants	38 participants n=5 Participants
Body Mass Index	30.8 kg/m^2 STANDARD_DEVIATION 4.3 • n=5 Participants	30.4 kg/m^2 STANDARD_DEVIATION 4.0 • n=7 Participants	30.6 kg/m^2 STANDARD_DEVIATION 4.1 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 12 weeks

Population: Intent to treat analysis population.

Total Disposition Index (DI) is a calculated value which represents the ability of a person's pancreas to lower blood glucose. A higher number means the pancreas is better able to lower blood glucose and a lower number means the pancreas is less able to lower blood glucose.

Outcome measures

Measure	Colesevelam n=19 Participants Treatment with colesevelam in addition to metformin and diet	Placebo n=19 Participants Placebo plus diet and metformin
Total Disposition Index Disposition Index at Baseline	332 DItot (10^-14 dl/kg/min^2 per pmol/l) Standard Error 41	253 DItot (10^-14 dl/kg/min^2 per pmol/l) Standard Error 40
Total Disposition Index Disposition Index at 12 Weeks	519 DItot (10^-14 dl/kg/min^2 per pmol/l) Standard Error 169	310 DItot (10^-14 dl/kg/min^2 per pmol/l) Standard Error 48

SECONDARY outcome

Timeframe: Baseline, 12 weeks

GLP-1 is thought to increase insulin secretion and was measured in the blood and reported in picomoles per liter.

Outcome measures

Measure	Colesevelam n=19 Participants Treatment with colesevelam in addition to metformin and diet	Placebo n=19 Participants Placebo plus diet and metformin
Total Fasting Glucagon-Like Peptide-1 (GLP-1) Concentration Total GLP-1 at Baseline	18.3 pmol/L Standard Error 1.8	18.6 pmol/L Standard Error 1.7
Total Fasting Glucagon-Like Peptide-1 (GLP-1) Concentration Total GLP-1 at 12 Weeks	21.9 pmol/L Standard Error 2.1	19.3 pmol/L Standard Error 2.4

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Fasting glucose concentrations were measured at baseline and 2 hours post-meal using the glucose oxidase method.

Outcome measures

Measure	Colesevelam n=19 Participants Treatment with colesevelam in addition to metformin and diet	Placebo n=19 Participants Placebo plus diet and metformin
Plasma Glucose Concentration Glucose at Baseline	7.0 mmol/L Standard Error 0.2	7.4 mmol/L Standard Error 0.3
Plasma Glucose Concentration Glucose at 12 Weeks	6.6 mmol/L Standard Error 0.2	7.5 mmol/L Standard Error 0.5
Plasma Glucose Concentration Postmeal Glucose Peak at Baseline	15.4 mmol/L Standard Error 0.6	15.4 mmol/L Standard Error 0.6
Plasma Glucose Concentration Postmeal Glucose Peak at 12 Weeks	14.4 mmol/L Standard Error 0.6	15.8 mmol/L Standard Error 0.6

SECONDARY outcome

Timeframe: Baseline, 12 weeks

HbA1c is the percent of red blood cell hemoglobin with glucose attached to it and an indicator of average blood glucose over the previous two to three months.

Outcome measures

Measure	Colesevelam n=19 Participants Treatment with colesevelam in addition to metformin and diet	Placebo n=19 Participants Placebo plus diet and metformin
Glycosylated Hemoglobin (HbA1c) HbA1c at Baseline	6.7 Percentage of hemoglobin Standard Error 0.1	6.8 Percentage of hemoglobin Standard Error 0.1
Glycosylated Hemoglobin (HbA1c) HbA1c at 12 Weeks	6.5 Percentage of hemoglobin Standard Error 0.2	6.9 Percentage of hemoglobin Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Fasting insulin levels were measured in the plasma using a chemiluminescence assay and is reported in nanomoles over 6 hours.

Outcome measures

Measure	Colesevelam n=19 Participants Treatment with colesevelam in addition to metformin and diet	Placebo n=19 Participants Placebo plus diet and metformin
Insulin Concentration Insulin at Baseline	48 nmols/6 hrs Standard Error 6	50 nmols/6 hrs Standard Error 6
Insulin Concentration Insulin at 12 Weeks	45 nmols/6 hrs Standard Error 5	51 nmols/6 hrs Standard Error 6
Insulin Concentration Postmeal Insulin at Baseline	67.3 nmols/6 hrs Standard Error 7.9	72.7 nmols/6 hrs Standard Error 8.3
Insulin Concentration Postmeal Insulin at 12 Weeks	63.9 nmols/6 hrs Standard Error 6.1	81.9 nmols/6 hrs Standard Error 11.6

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

EGP was measured using a triple-tracer mixed meal and calculated using the Steele's model, reported in micromoles per kilogram per minute.

Outcome measures

Measure	Colesevelam n=19 Participants Treatment with colesevelam in addition to metformin and diet	Placebo n=19 Participants Placebo plus diet and metformin
Fasting Endogenous Glucose Production (EGP) EGP at Baseline	17.6 micromol/kg/min Standard Error 0.6	17.7 micromol/kg/min Standard Error 0.7
Fasting Endogenous Glucose Production (EGP) EGP at 12 Weeks	17.2 micromol/kg/min Standard Error 0.6	17.6 micromol/kg/min Standard Error 0.7

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Meal Ra was measured using a triple-tracer mixed meal and reported in micromols in 6 hours. Meal derived glucose is a function of both gastric emptying and splanchnic meal extraction. Meal Ra was calculated by multiplying rate of appearance of [1-^13C] glucose (obtained from the infusion rate of [6-^3H] glucose and the clamped plasma ratio of [6-^3H] glucose and [1-^13C] glucose) by the meal enrichment.

Outcome measures

Measure	Colesevelam n=19 Participants Treatment with colesevelam in addition to metformin and diet	Placebo n=19 Participants Placebo plus diet and metformin
Rate of Meal Glucose Appearance (Meal Ra) Meal appearance glucose at Baseline	5941 micromol/6h Standard Error 402	5504 micromol/6h Standard Error 354
Rate of Meal Glucose Appearance (Meal Ra) Meal appearance glucose at 12 Weeks	5413 micromol/6h Standard Error 289	5613 micromol/6h Standard Error 354

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Meal Rd is the rate at which glucose leaves the systemic circulation. It was measured using a triple-tracer mixed meal and reported in micromols over 6 hours. Meal Rd was calculated by subtracting the change in glucose mass from the overall rate of glucose appearance (i.e., meal Ra + EGP).

Outcome measures

Measure	Colesevelam n=19 Participants Treatment with colesevelam in addition to metformin and diet	Placebo n=19 Participants Placebo plus diet and metformin
Rate of Meal Glucose Disappearance (Meal Rd) Meal Rd at Baseline	8642 micromol/6h Standard Error 414	8784 micromol/6h Standard Error 403
Rate of Meal Glucose Disappearance (Meal Rd) Meal Rd at 12 Weeks	8155 micromol/6h Standard Error 314	8761 micromol/6h Standard Error 382

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Lipids are fat-like substances in the blood.

Outcome measures

Measure	Colesevelam n=19 Participants Treatment with colesevelam in addition to metformin and diet	Placebo n=19 Participants Placebo plus diet and metformin
Lipid Values Total Cholesterol at Baseline	4.35 mmol/l Standard Error 0.19	4.33 mmol/l Standard Error 0.14
Lipid Values Total Cholesterol at 12 weeks	3.60 mmol/l Standard Error 0.16	4.00 mmol/l Standard Error 0.14
Lipid Values Triglycerides at Baseline	1.67 mmol/l Standard Error 0.15	1.88 mmol/l Standard Error 0.27
Lipid Values Triglycerides at 12 Weeks	2.19 mmol/l Standard Error 0.19	1.55 mmol/l Standard Error 0.18
Lipid Values High Density Lipoprotein (HDL) at Baseline	1.18 mmol/l Standard Error 0.06	1.27 mmol/l Standard Error 0.08
Lipid Values High Density Lipoprotein (HDL) at 12 Weeks	1.08 mmol/l Standard Error 0.10	1.20 mmol/l Standard Error 0.07
Lipid Values Low Density Lipoprotein (LDL) at Baseline	2.50 mmol/l Standard Error 0.17	2.31 mmol/l Standard Error 0.13
Lipid Values Low Density Lipoprotein (LDL) at 12 Weeks	1.59 mmol/l Standard Error 0.14	2.09 mmol/l Standard Error 0.12

Adverse Events

Colesevelam

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Colesevelam n=19 participants at risk Treatment with colesevelam in addition to metformin and diet	Placebo n=19 participants at risk Placebo plus diet and metformin
Gastrointestinal disorders GI ulcer and hemorrhage	5.3% 1/19 • Number of events 1 • Baseline to 12 weeks.	0.00% 0/19 • Baseline to 12 weeks.

Other adverse events

Measure	Colesevelam n=19 participants at risk Treatment with colesevelam in addition to metformin and diet	Placebo n=19 participants at risk Placebo plus diet and metformin
Blood and lymphatic system disorders Low hemoglobin	5.3% 1/19 • Number of events 1 • Baseline to 12 weeks.	0.00% 0/19 • Baseline to 12 weeks.

Additional Information

Dr. Adrian Vella

Mayo Clinic

Phone: 507-284-3289

Email: vella.adrian@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place