Trial Outcomes & Findings for The Effect of Exenatide Compared to Lantus Insulin on Vascular Function in Type 2 Diabetes (NCT NCT00353834)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

72 participants

Primary outcome timeframe

Baseline and End of Study

Results posted on

2018-01-09

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Glargine Insulin 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 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 Study STARTED	26	27
Overall Study COMPLETED	26	27
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glargine Insulin n=26 Participants 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 n=27 Participants 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 n=53 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	26 Participants n=93 Participants	27 Participants n=4 Participants	53 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	60.4 years STANDARD_DEVIATION 8.5 • n=93 Participants	58.4 years STANDARD_DEVIATION 11.6 • n=4 Participants	59.4 years STANDARD_DEVIATION 10.0 • n=27 Participants
Sex: Female, Male Female	10 Participants n=93 Participants	12 Participants n=4 Participants	22 Participants n=27 Participants
Sex: Female, Male Male	16 Participants n=93 Participants	15 Participants n=4 Participants	31 Participants n=27 Participants
Region of Enrollment United States	26 participants n=93 Participants	27 participants n=4 Participants	53 participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and End of Study

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.

Outcome measures

Outcome measures
Measure	Glargine Insulin n=26 Participants 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 n=27 Participants 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
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.	5.0 Percentage dilation Standard Deviation 2.3	4.7 Percentage dilation Standard Deviation 2.4

SECONDARY outcome

Timeframe: Baseline and end of study

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.

Outcome measures

Outcome measures
Measure	Glargine Insulin n=26 Participants 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 n=27 Participants 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
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	10.7 Percentage dilation Standard Deviation 5.3	11.3 Percentage dilation Standard Deviation 4.5

SECONDARY outcome

Timeframe: Baseline and end of study

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and end of study

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and end of study

Outcome measures

Outcome data not reported

Adverse Events

Glargine Insulin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Exenatide

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Edward S. Horton, MD

Joslin Diabetes Center

Phone: 6173091995

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place