Trial Outcomes & Findings for Adding Liraglutide to High Dose Insulin: Breaking the Cycle (NCT NCT01505673)

NCT ID: NCT01505673

Last Updated: 2018-01-16

Results Overview

HbA1c (%)

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 71 participants
• Primary outcome timeframe: 6-months
• Results posted on: 2018-01-16

Participant Flow

Participant milestones

Measure	Liraglutide Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection Saline: Placebo injection of 1.8mg saline once daily for 6-months
Overall Study STARTED	35	36
Overall Study COMPLETED	32	34
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Adding Liraglutide to High Dose Insulin: Breaking the Cycle

Baseline characteristics by cohort

Measure	Liraglutide n=35 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=36 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months	Total n=71 Participants Total of all reporting groups
Age, Categorical Between 18 and 65 years	35 Participants n=5 Participants	36 Participants n=7 Participants	71 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	52.8 years STANDARD_DEVIATION 8.1 • n=5 Participants	55.5 years STANDARD_DEVIATION 6.6 • n=7 Participants	54.2 years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment United States	32 Participants n=5 Participants	34 Participants n=7 Participants	66 Participants n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6-months

HbA1c (%)

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Glycemic Control Measured by HbA1c	7.9 Percent HbA1c Standard Deviation 1.1	8.9 Percent HbA1c Standard Deviation 1.3

SECONDARY outcome

Timeframe: 6-months

Liver Triglyceride and Pancreatic Triglyceride

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Pancreatic and Hepatic Triglyceride Content Pancreatic Triglyceride	12.53 Percent Triglyceride Standard Deviation 8.13	14.64 Percent Triglyceride Standard Deviation 9.25
Pancreatic and Hepatic Triglyceride Content Liver Triglyceride	12.3 Percent Triglyceride Standard Deviation 5.8	12.2 Percent Triglyceride Standard Deviation 7.8

SECONDARY outcome

Timeframe: 6-months

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Weight	114 Kilograms Standard Deviation 21	117 Kilograms Standard Deviation 27

SECONDARY outcome

Timeframe: 6-months

Fasting Glucose as a Measure of Beta-Cell Function

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Beta-Cell Function	179 mg/dL Standard Deviation 75	197 mg/dL Standard Deviation 98

SECONDARY outcome

Timeframe: 6-months

Measured during mixed meal challenge test.

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Glucagon	107.3 pg/mL Standard Deviation 44.5	93.8 pg/mL Standard Deviation 37.8

SECONDARY outcome

Timeframe: 6-months

The 3 days average of the total daily dose of insulin used within 3 consecutive days prior office visit 6 month.

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Total Daily Insulin Dose	200 IU Interval 163.0 to 275.0	218 IU Interval 160.0 to 260.0

SECONDARY outcome

Timeframe: 6-months

The 3 days average of the number of daily injections performed within 3 consecutive days prior office visit 6 month.

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Number of Daily Injections	3.7 number/day Standard Deviation 1.4	3.8 number/day Standard Deviation 1.3

SECONDARY outcome

Timeframe: 6-months

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Blood Pressure Systolic	134 mmHg Standard Deviation 18	135 mmHg Standard Deviation 17
Blood Pressure Diastolic	80.5 mmHg Standard Deviation 13.7	74.3 mmHg Standard Deviation 9.7

SECONDARY outcome

Timeframe: 6-months

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Lipid Profile Total cholesterol	154 mg/dL Standard Deviation 41	152 mg/dL Standard Deviation 42
Lipid Profile LDL	83.9 mg/dL Standard Deviation 37.2	76.3 mg/dL Standard Deviation 28.4
Lipid Profile HDL	36.6 mg/dL Standard Deviation 9.8	37.6 mg/dL Standard Deviation 9.9

SECONDARY outcome

Timeframe: 6-months

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Liver Function Blood Test AST	26.4 U/L Standard Deviation 17.6	32.1 U/L Standard Deviation 30.0
Liver Function Blood Test ALT	25.8 U/L Standard Deviation 13.5	36.0 U/L Standard Deviation 43.7

SECONDARY outcome

Timeframe: 6-months

Reported as hypoglycemic events per month by patient as any blood glucose <70 mg/dl or symptoms of hypoglycemia with blood glucose >70 mg/dl

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Hypoglycemic Events	1.1 events per month per patient Interval 0.7 to 1.7	0.7 events per month per patient Interval 0.5 to 1.2

SECONDARY outcome

Timeframe: 6-months

General health perception was measured at randomization and 6 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 = excellent; 2 = very good; 3 = good; 4 = fair; 5 = poor.

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Quality of Life Survey (QoL) - General Health Perception	3.1 score on a scale Standard Deviation 0.9	3.6 score on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: 6 months

Fasting C-peptide as a Measure of Beta-Cell Function

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Beta-Cell Function	2.48 microgram/L Standard Deviation 1.18	1.75 microgram/L Standard Deviation 1.19

SECONDARY outcome

Timeframe: 6 months

The Matsuda index is a measure of insulin sensitivity and has no minimum/maximum values. Index values are calculated as 500,000/square root of ((fasting glucose x fasting c-peptide x 333) x (mean 120 min post-meal glucose x mean 120 min post-meal c-peptide x 333)). Higher/lower values = better/worse insulin sensitivity.

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Matsuda Index as a Measure of Beta Cell Function	2.88 index Interval 1.67 to 3.7	3.12 index Interval 1.78 to 9.7

SECONDARY outcome

Timeframe: 6 Months

AUC c-peptide

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Beta-cell Function	1234.6 ug/(L/min) Standard Deviation 588.6	922.9 ug/(L/min) Standard Deviation 470.5

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Ratio (AUC C-peptide/AUC Glucose)	0.019 Ratio Standard Deviation 0.010	0.013 Ratio Standard Deviation 0.008

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Measure	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
AUC Glucose	71747 mg/(dL/min) Standard Deviation 22141	79278 mg/(dL/min) Standard Deviation 29416

SECONDARY outcome

Timeframe: 6 months

Current health perception was measured at randomization and 6 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	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Quality of Life Survey (QoL) - Current Health Perception	2.1 score on a scale Standard Deviation 0.9	2.6 score on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: 6 months

Quality of Life Survey (QoL) - treatment satisfactionTreatment satisfaction was measured at randomization and 6 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	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Quality of Life Survey (QoL) - Treatment Satisfaction	2.4 score on a scale Standard Deviation 0.8	2.7 score on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: 6 months

Treatment impact was measured at randomization and 6 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	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Quality of Life Survey (QoL) - Treatment Impact	2.3 score on a scale Standard Deviation 0.5	2.6 score on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: 6 months

Social or vocational worry was measured at randomization and 6 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	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Quality of Life Survey (QoL) - Social or Vocational Worry	1.5 score on a scale Standard Deviation 0.7	1.0 score on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: 6 months

Hypoglycemia fear was measured at randomization and 6 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	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Quality of Life Survey (QoL) - Hypoglycemia Fear	1.9 score on a scale Standard Deviation 0.7	2.0 score on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: 6 months

Glycemia control perception was measured at randomization and 6 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	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Quality of Life Survey (QoL) - Glycemia Control Perception	2.0 score on a scale Standard Deviation 1.0	2.9 score on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: 6 months

Lifestyle flexibility was measured at randomization and 6 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	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Quality of Life Survey (QoL) - Lifestyle Flexibility	2.2 score on a scale Standard Deviation 0.9	2.6 score on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: 6 months

Social stigma was measured at randomization and 6 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	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Quality of Life Survey (QoL) - Social Stigma	2.5 score on a scale Standard Deviation 1.1	2.4 score on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: 6 months

Satisfaction with insulin treatment was measured at randomization and 6 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	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment	1.6 score on a scale Standard Deviation 1.0	2.3 score on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: 6 months

Willingness to continue insulin treatment was measured at randomization and 6 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	Liraglutide n=32 Participants Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=34 Participants Saline: Placebo injection of 1.8mg saline once daily for 6-months
Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment	1.0 score on a scale Standard Deviation 0.5	2.1 score on a scale Standard Deviation 1.3

Adverse Events

Liraglutide

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Saline Injection

Serious events: 6 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	Liraglutide n=35 participants at risk Liraglutide: Liraglutide 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=36 participants at risk Saline: Placebo injection of 1.8mg saline once daily for 6-months
Cardiac disorders Atrial fibrilation	2.9% 1/35 • Number of events 1 • 6 months	0.00% 0/36 • 6 months
Respiratory, thoracic and mediastinal disorders COPD exacerbation	0.00% 0/35 • 6 months	2.8% 1/36 • Number of events 1 • 6 months
Cardiac disorders Stent placement	0.00% 0/35 • 6 months	5.6% 2/36 • Number of events 2 • 6 months
Gastrointestinal disorders Acute cholecystitis	0.00% 0/35 • 6 months	2.8% 1/36 • Number of events 1 • 6 months
Skin and subcutaneous tissue disorders Cellulitis	0.00% 0/35 • 6 months	2.8% 1/36 • Number of events 1 • 6 months
Gastrointestinal disorders Gastroenteritis	0.00% 0/35 • 6 months	2.8% 1/36 • Number of events 1 • 6 months

Other adverse events

Measure	Liraglutide n=35 participants at risk Liraglutide: Liraglutide 1.8mg injected subcutaneously from pen device once daily for 6-months	Saline Injection n=36 participants at risk Saline: Placebo injection of 1.8mg saline once daily for 6-months
Gastrointestinal disorders Nausea	31.4% 11/35 • Number of events 11 • 6 months	19.4% 7/36 • Number of events 7 • 6 months
Gastrointestinal disorders Diarrhea	11.4% 4/35 • Number of events 4 • 6 months	8.3% 3/36 • Number of events 3 • 6 months
Nervous system disorders Headache	8.6% 3/35 • Number of events 3 • 6 months	13.9% 5/36 • Number of events 5 • 6 months
Gastrointestinal disorders Vomiting	5.7% 2/35 • Number of events 2 • 6 months	2.8% 1/36 • Number of events 1 • 6 months
Gastrointestinal disorders Decreased in apetite	17.1% 6/35 • Number of events 6 • 6 months	11.1% 4/36 • Number of events 4 • 6 months
Gastrointestinal disorders Abdominal discomfort	2.9% 1/35 • Number of events 1 • 6 months	2.8% 1/36 • Number of events 1 • 6 months
Gastrointestinal disorders Increase of serum amylase	2.9% 1/35 • Number of events 1 • 6 months	2.8% 1/36 • Number of events 1 • 6 months
Respiratory, thoracic and mediastinal disorders Cough	2.9% 1/35 • Number of events 1 • 6 months	8.3% 3/36 • Number of events 3 • 6 months
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/35 • 6 months	2.8% 1/36 • Number of events 1 • 6 months
Respiratory, thoracic and mediastinal disorders Shortness of breath	2.9% 1/35 • Number of events 1 • 6 months	0.00% 0/36 • 6 months

Additional Information

Dr. Ildiko Lingvay

University of Texas Southwestern Medical Center at Dallas

Phone: 214-648-2779

Email: ildiko.lingvay@utsouthwestern.edu

Results disclosure agreements

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