Impaired Glucose Tolerance
Conditions
Brief summary
The purpose of this study is to compare the effects of exenatide versus metformin on vascular health with chronic (3-month) therapy and during a 2-hour period following a meal in patients with pre-diabetes. It is predicted that exenatide will improve vascular health to a greater degree compared to metformin.
Interventions
DRUGMetformin
metformin 500 twice daily
DRUGExenatide
exenatide 10 mcg twice daily
Sponsors
Amylin Pharmaceuticals, LLC.
Eli Lilly and Company
International Diabetes Center at Park Nicollet
St. Paul Heart Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Greater than or equal to 18 years old * Impaired glucose tolerance: 2-hr oral glucose tolerance test (OGTT) plasma glucose \>140 mg/dL OR impaired fasting glucose: fasting glucose \> or = 100 mg/dL OR elevated glycosylated hemoglobin: Hemoglobin A1c \> or = 5.7% * Abdominal obesity: waist circumference \>102 cm (men) and \>88 cm (women) * Stable cardiovascular medication regimen (or other medications known to affect endothelial function) at least 1 month prior to enrollment and throughout the study
Exclusion criteria
* Type 2 diabetes * Current use of glycemic control medications within one month of randomization * Fasting glucose \>126 mg/dL * Current use of weight loss medication * Previous weight loss surgery * History of severe gastrointestinal disease * Standard clinical contraindications to exenatide or metformin therapy * Unstable angina * Heart failure * Stroke or coronary artery bypass graft within 3 months of screening * Women who are currently pregnant or planning to become pregnant * Breastfeeding women * Clinically significant liver disease * Creatinine \> 1.5 mg/dL * Hepatic function greater than 3 times upper limit of normal * Patients who are mentally incompetent and cannot sign a Patient Informed Consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Reactive Hyperemic Index Over the 3-month Treatment Period | Change from baseline to 3 months | Change in reactive hyperemic index over the 3-month treatment period, which is a measure of endothelial (inner lining of blood vessels) function. This is measured as a ratio of post-occlusion blood flow volume versus baseline blood flow volume in fingertips. Higher ratio values are considered indicative of better arterial health. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from medical clinics
Participants by arm
| Arm | Count |
|---|---|
| Exenatide Three months of Exenatide therapy. Exenatide was initiated at 5 mcg, twice a day for one month and then up titrated to 10 mcg, twice a day for the remaining two months. | 25 |
| Metformin Three months of Metformin therapy. Metformin was initiated at 500 mcg, twice a day for one month and then up titrated to 1000 mcg, twice a day for the remaining two months. | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Metformin | Exenatide | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 25 Participants | 50 Participants |
| Age Continuous | 58.4 years STANDARD_DEVIATION 10.1 | 58.7 years STANDARD_DEVIATION 10 | 58.5 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 25 participants | 25 participants | 50 participants |
| Sex: Female, Male Female | 18 Participants | 20 Participants | 38 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 0 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Change in Reactive Hyperemic Index Over the 3-month Treatment Period
Change in reactive hyperemic index over the 3-month treatment period, which is a measure of endothelial (inner lining of blood vessels) function. This is measured as a ratio of post-occlusion blood flow volume versus baseline blood flow volume in fingertips. Higher ratio values are considered indicative of better arterial health.
Time frame: Change from baseline to 3 months
Population: All completers were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Change in Reactive Hyperemic Index Over the 3-month Treatment Period | 0.01 ratio | Standard Deviation 0.68 |
| Metformin | Change in Reactive Hyperemic Index Over the 3-month Treatment Period | -0.17 ratio | Standard Deviation 0.72 |