Trial Outcomes & Findings for Preservation of Beta-cell Function in Type 2 Diabetes Mellitus (NCT NCT00232583)

NCT ID: NCT00232583

Last Updated: 2017-12-14

Results Overview

C-peptide AUC during a 3-hours mixed meal challenge testing

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 58 participants
• Primary outcome timeframe: 72 months
• Results posted on: 2017-12-14

Participant Flow

Patients recruited at UT Southwestern Clinical Diabetes Research Office

A 3-months run-in period preceeded randomization. During this period all patients were treated with insulin and metformin.

Participant milestones

Measure	Metfomin & Insulin Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metfomin, Pioglitazone & Glyburide Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Overall Study STARTED	29	29
Overall Study COMPLETED	19	16
Overall Study NOT COMPLETED	10	13

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Preservation of Beta-cell Function in Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Measure	Metfomin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metfomin, Pioglitazone & Glyburide n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).	Total n=58 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	29 Participants n=93 Participants	29 Participants n=4 Participants	58 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	44.8 years STANDARD_DEVIATION 9.7 • n=93 Participants	45.0 years STANDARD_DEVIATION 10.7 • n=4 Participants	44.9 years STANDARD_DEVIATION 10.1 • n=27 Participants
Sex: Female, Male Female	9 Participants n=93 Participants	12 Participants n=4 Participants	21 Participants n=27 Participants
Sex: Female, Male Male	20 Participants n=93 Participants	17 Participants n=4 Participants	37 Participants n=27 Participants
Region of Enrollment United States	29 participants n=93 Participants	29 participants n=4 Participants	58 participants n=27 Participants

PRIMARY outcome

Timeframe: 72 months

C-peptide AUC during a 3-hours mixed meal challenge testing

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Beta-cell Function - C-peptide AUC (Area Under the Curve)	2096 ng*min/mL Standard Deviation 795	1725 ng*min/mL Standard Deviation 618

SECONDARY outcome

Timeframe: 72 months

C-peptide-based Matsuda index using following formula: Matsuda index = 500,00 / root square [(fasting c-peptide x fasting glucose x 333) x (average c-peptide 0-120 mins x average glucose 0-120 mins x 333). Higher the Matsuda index, better the insulin sensitivity.

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Insulin Sensitivity as Measure be Matsuda Index	3.12 index Standard Deviation 2.62	2.45 index Standard Deviation 1.09

SECONDARY outcome

Timeframe: 72 months

Disposition index was measured by multiplying the insulin secretion (C-peptide AUC/C-peptide AUC glucose) by the Matsuda index. Disposition index reflects the beta-cell function adjusted for total body insulin sensitivity

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Bet-cell Function Measured by Disposition Index	0.12 index Standard Deviation 0.07	0.16 index Standard Deviation 0.09

SECONDARY outcome

Timeframe: 72 months

Body Weight

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Weight	107.7 kg Standard Deviation 31.1	107.9 kg Standard Deviation 31.4

SECONDARY outcome

Timeframe: 72 months

Inflammatory markers - hsCRP (C reactive protein)

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Inflammatory Markers - hsCRP	6.9 mg/L Standard Deviation 7.7	6.1 mg/L Standard Deviation 8.9

SECONDARY outcome

Timeframe: 72 months

Inflammatory markers - Fibrinogen

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Inflammatory Markers -Fibrinogen	399.0 mg/dL Standard Deviation 82.6	395.4 mg/dL Standard Deviation 98.5

SECONDARY outcome

Timeframe: 72 months

Inflammatory markers - PAI-1 (Plasminogen activator inhibitor type 1)

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Inflammatory Markers - PAI-1	13.9 IU/L Standard Deviation 11.7	16.7 IU/L Standard Deviation 18.0

SECONDARY outcome

Timeframe: 72 months

Current health perception was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 = much better than 3 months ago; 2 - Somewhat better now than 3 months ago; 3 - About the same; 4 - Somewhat worse now than 3 months ago; 5 Much worse now than 3 months ago.

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Quality of Life Survey (QoL) - Current Health Perception	2.7 score on a scale Standard Deviation 0.9	2.9 score on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: 72 months

Treatment satisfaction was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Quality of Life Survey (QoL) - Treatment Satisfaction	1.7 score on a scale Standard Deviation 0.5	2.1 score on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: 72 months

Treatment impact was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Quality of Life Survey (QoL) - Treatment Impact	1.7 score on a sale Standard Deviation 0.2	1.8 score on a sale Standard Deviation 0.3

SECONDARY outcome

Timeframe: 72 months

Social or vocational worry was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 0-5, where 0 - does not apply; 1 - never; 2 - seldom; 3 - sometimes; 4 - often; 5 - all of the time.

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Quality of Life Survey (QoL) - Social or Vocational Worry	1.8 score on a scale Standard Deviation 0.3	1.7 score on a scale Standard Deviation 0.3

SECONDARY outcome

Timeframe: 72 months

Hypoglycemia fear was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - never worry; 2 - rarely water; 3 - sometimes worry; 4 - often worry; 5 - very often worry

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Quality of Life Survey (QoL) - Hypoglycemia Fear	1.8 score on a scale Standard Deviation 0.3	1.8 score on a scale Standard Deviation 0.4

SECONDARY outcome

Timeframe: 72 months

Glycemia control perception was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1-7, where 1 - extremely controlled and 7 - not at all controlled.

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Quality of Life Survey (QoL) - Glycemia Control Perception	2.8 score on a scale Standard Deviation 2.8	2.0 score on a scale Standard Deviation 2.0

SECONDARY outcome

Timeframe: 72 months

Lifestyle flexibility was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1 to 5, where 1 - a great deal of choice; 2 - a lot of choice; 3 - some choice; 4 - a little choice; 5 - no choice.

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Quality of Life Survey (QoL) - Lifestyle Flexibility	2.1 score on a scale Standard Deviation 0.6	2.0 score on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: 72 months

Social stigma was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1 to 5, where 1- strongly agree; 2 - somewhat agree; 3 - neither agree nor disagree; 4 - somewhat disagree; 5 - strongly disagree.

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone n=29 Participants Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Quality of Life Survey (QoL) - Social Stigma	2.2 score on a scale Standard Deviation 1.2	2.2 score on a scale Standard Deviation 1.7

SECONDARY outcome

Timeframe: 72 months

Population: Data were not collected from participants in the "Metfomin, Pioglitazone \& Glyburide" Arm/Group since patients did not receive insulin.

Satisfaction with insulin treatment was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1 to 7, where 1 extremely satisfied to 7 - not at all satisfied.

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment	1.2 score on a scale Standard Deviation 0.9	—

SECONDARY outcome

Timeframe: 72 months

Population: Data were not collected from participants in the "Metfomin, Pioglitazone \& Glyburide" Arm/Group since patients did not receive insulin.

Willingness to continue insulin treatment was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1 to 7, where 1 extremely willing to 7 - not at all willing.

Outcome measures

Measure	Metformin & Insulin n=29 Participants Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metformin, GLyburide & Pioglitazone Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment	1.4 score on a scale Standard Deviation 0.7	—

Adverse Events

Metfomin & Insulin

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Metfomin, Pioglitazone & Glyburide

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Metfomin & Insulin n=29 participants at risk Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metfomin, Pioglitazone & Glyburide n=29 participants at risk Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Cardiac disorders Cardiac arrest	3.4% 1/29 • Number of events 1	3.4% 1/29 • Number of events 1

Other adverse events

Measure	Metfomin & Insulin n=29 participants at risk Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose).	Metfomin, Pioglitazone & Glyburide n=29 participants at risk Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily).
Gastrointestinal disorders GI disturbance	17.2% 5/29 • Number of events 15	20.7% 6/29 • Number of events 18

Additional Information

Ildiko Lingvay

UT Southwestern Medical Center

Phone: 214-648-2779

Email: ildiko.lingvay@utsouthwestern.edu

Results disclosure agreements

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