The Effect of Exenatide Compared to Lantus Insulin on Vascular Function in Type 2 Diabetes

• ClinicalTrials.gov Identifier: NCT00353834
• Recruitment Status: Completed
• First Posted: July 19, 2006
• Results First Posted: January 9, 2018
• Last Update Posted: January 9, 2018
• Sponsor: Joslin Diabetes Center
• Collaborators: Amylin Pharmaceuticals, LLC.; Eli Lilly and Company
• Information provided by (Responsible Party): Joslin Diabetes Center

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Type 2 Diabetes Mellitus
• Interventions: Drug: Exenatide; Drug: Glargine Insulin
• Enrollment: 72

Participant Flow

Recruitment Details	Subjects were recruited from the Joslin Diabetes Center Clinic, Boston, MA, from July 2006-0ctober 2009. Subjects had Type 2 diabetes, treated with either Metformin, SU, Metformin/SU, TZD, or Metformin/TZD, on stable therapy and weight for 3 months. The healthy controls in the Extension Study, were recruited from the Joslin Diabetes Center.
Pre-assignment Details	Baseline fasting studies on all subjects included anthropometrics, blood pressure, HbA1c, glucose, insulin, c-peptide, lipids, free fatty acids (FFA), hsCRP, TNFa, IL-6, siCAM, sVCAM, PAI-1 antigen, and oxidized LDL. PWA and FMD were measured fasting and after a standardized meal with repeat PWA and FMD at 2 and 4 hours, and TNG at 4 hours.

Arm/Group Title	Glargine Insulin	Exenatide
Arm/Group Description	Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve fasting blood glucose of 100 mg/dl and avoid hypoglycemia. Glargine Insulin: Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve a fasting glucose of 100mg/dl and avoid hypoglycemia.	Exenatide 5ug twice daily for 4 weeks followed by 10 ug twice daily for 8 weeks. Exenatide: Exenetide 5ug twice daily for 4 weeks, then 10ug twice daily for 8 weeks
Period Title: Overall Study
Started	26	27
Completed	26	27
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Glargine Insulin	Exenatide	Total
Arm/Group Description		Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve fasting blood glucose of 100 mg/dl and avoid hypoglycemia. Glargine Insulin: Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve a fasting glucose of 100mg/dl and avoid hypoglycemia.	Exenatide 5ug twice daily for 4 weeks followed by 10 ug twice daily for 8 weeks. Exenatide: Exenetide 5ug twice daily for 4 weeks, then 10ug twice daily for 8 weeks	Total of all reporting groups
Overall Number of Baseline Participants		26	27	53
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants	27 participants	53 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	26 100.0%	27 100.0%	53 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	26 participants	27 participants	53 participants
		60.4 (8.5)	58.4 (11.6)	59.4 (10.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants	27 participants	53 participants
	Female	10 38.5%	12 44.4%	22 41.5%
	Male	16 61.5%	15 55.6%	31 58.5%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	26 participants	27 participants	53 participants
		26	27	53

Outcome Measures

1. Primary Outcome

Title	The Primary Endpoint Was the Change in FMD at the End of the Study Compared to Baseline Measurements in Subjects Treated With Exenatide Compared to Subjects Treated With Lantus.
Description	Flow mediated dilation (FMD) of the brachial artery was measured at rest and during reactive hyperemia using a high-resolution 10.0 MHz linear array transducer and an HOI Ultramark 9 system. Reactive hyperemia was produced by inflating a pneumatic tourniquet on the forearm distal to the brachial artery to 50 mmHg above the systolic BP for 5 minutes, then deflating it . Brachial artery diameter was measured before inflation of the cuff and 1-2 minutes after cuff deflation and expressed as the percentage change. This protocol is described in detail elsewhere. This was performed fasting, 2, and 4 hours after the meal challenge at baseline and 3 months.
Time Frame	Baseline and End of Study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glargine Insulin	Exenatide
Arm/Group Description:	Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve fasting blood glucose of 100 mg/dl and avoid hypoglycemia. Glargine Insulin: Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve a fasting glucose of 100mg/dl and avoid hypoglycemia.	Exenatide 5ug twice daily for 4 weeks followed by 10 ug twice daily for 8 weeks. Exenatide: Exenetide 5ug twice daily for 4 weeks, then 10ug twice daily for 8 weeks
Overall Number of Participants Analyzed	26	27
Mean (Standard Deviation); Unit of Measure: Percentage dilation
	5.0 (2.3)	4.7 (2.4)

2. Secondary Outcome

Title	First Will be the Changes in TNG Stimulated Arterial Dilation (Endothelial-independent) in Subjects Treated With Exenatide Compared With Subjects Treated With Lantus at the End of the Study Compared to Baseline Measurements
Description	Trinitroglycerin (TNG) response evaluates endothelium independent vasodilation. The brachial artery was scanned before and 5 minutes after sublingual administration of 400 ug of trinitroglycerin. This was performed only at 4 hours following the test meal and fifteen minutes after completion of the FMD study to allow for the brachial artery to return to baseline. This was performed at both the baseline and 3 month visits.
Time Frame	Baseline and end of study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glargine Insulin	Exenatide
Arm/Group Description:	Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve fasting blood glucose of 100 mg/dl and avoid hypoglycemia. Glargine Insulin: Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve a fasting glucose of 100mg/dl and avoid hypoglycemia.	Exenatide 5ug twice daily for 4 weeks followed by 10 ug twice daily for 8 weeks. Exenatide: Exenetide 5ug twice daily for 4 weeks, then 10ug twice daily for 8 weeks
Overall Number of Participants Analyzed	26	27
Mean (Standard Deviation); Unit of Measure: Percentage dilation
	10.7 (5.3)	11.3 (4.5)

3. Secondary Outcome

Title	Second Will be the Change in Arterial Stiffness, as Measured by PWA, in Subjects Treated With Exenatide Compared With Subjects Treated With Lantus at the End of the Study Compared to Baseline Measurements.
Description	[Not Specified]
Time Frame	Baseline and end of study

Outcome Measure Data Not Reported

4. Secondary Outcome

Title	Third Will be the Changes in Markers of Endothelial Function, Inflammation, Fibrinolysis, and Oxidative Stress in Subjects Treated With Exenatide Compared With Subjects Treated With Lantus at the End of the Study Compared to Baseline
Description	[Not Specified]
Time Frame	Baseline and end of study

Outcome Measure Data Not Reported

5. Secondary Outcome

Title	Fourth Will be Changes in Insulin, Glucose, C-peptide, Lipids, and FFA Responses Following the MTT in Subjects Treated With Exenatide Compared With Subjects Treated With Lantus at the End of the Study Compared to Baseline Measurement
Description	[Not Specified]
Time Frame	Baseline and end of study

Outcome Measure Data Not Reported

Adverse Events

Time Frame	3 years and 3 months
Adverse Event Reporting Description	No adverse events reported
Arm/Group Title	Glargine Insulin	Exenatide
Arm/Group Description	Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve fasting blood glucose of 100 mg/dl and avoid hypoglycemia. Glargine Insulin: Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve a fasting glucose of 100mg/dl and avoid hypoglycemia.	Exenatide 5ug twice daily for 4 weeks followed by 10 ug twice daily for 8 weeks. Exenatide: Exenetide 5ug twice daily for 4 weeks, then 10ug twice daily for 8 weeks
All-Cause Mortality
	Glargine Insulin	Exenatide
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/26 (0.00%)	0/27 (0.00%)
Serious Adverse Events
	Glargine Insulin	Exenatide
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/26 (0.00%)	0/27 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Glargine Insulin	Exenatide
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/26 (0.00%)	0/27 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Edward S. Horton, MD
• Organization: Joslin Diabetes Center
• Phone: 6173091995
• EMail: edward.horton@joslin.harvard.edu

• Responsible Party: Joslin Diabetes Center
• ClinicalTrials.gov Identifier: NCT00353834
• Other Study ID Numbers: CHS #05-45
• First Submitted: July 18, 2006
• First Posted: July 19, 2006
• Results First Submitted: December 7, 2017
• Results First Posted: January 9, 2018
• Last Update Posted: January 9, 2018