Obesity
Conditions
Keywords
obesity, growth hormone
Brief summary
This study tests the following hypotheses: Aim 1: Test the hypothesis that acute dipeptidyl peptidase 4 (DPP4) inhibition with the currently available anti-diabetic drug, sitagliptin, will increase stimulated growth hormone (GH) secretion in healthy lean adults by decreasing the degradation of growth hormone releasing hormone (GHRH). Aim 2: Test the hypothesis that decreased degradation of GHRH during acute DPP4 inhibition will result in an increase in endothelium-dependent vasodilation mediated by GH and independent from GLP1 (glucagon like peptide-1) in healthy lean adults. This study promises to provide novel data regarding how this increasingly used class of anti-diabetic drugs affects the pituitary GH axis and could affect blood vessel relaxation. Growth hormone levels are low in the setting of obesity and pre-diabetes. A further study may evaluate the effect of chronic DPP4 inhibitor therapy in a population of patients with obesity and pre-diabetes.
Detailed description
Growth hormone secretion is low in patients with obesity, insulin resistance, and hyperlipidemia. GH therapy in these populations and others has been limited by side effects which include hyperglycemia. Another strategy to increase GH secretion is to enhance pulsatile GH secretion by growth hormone releasing hormone. Growth hormone releasing hormone (GHRH) has a half life of 5 minutes due to its rapid inactivation by DPP4. An alternative strategy to increase endogenous GH secretion is by inhibiting degradation of GHRH by DPP4. DPP4 inhibitors are currently approved therapies for the treatment of hyperglycemia in patients with type 2 diabetes mellitus. They additionally cause blood vessel relaxation. We therefore propose to test the hypothesis that DPP4 inhibition simultaneously enhances GH secretion while improving blood glucoses and vascular function in patient populations with low GH and increased cardiovascular risk. These preliminary aims serve primarily as a novel proof of concept study to define the effect of acute pharmacologic DPPIV inhibition on stimulated GH secretion.
Interventions
DRUGSitagliptin
During Aim 1, given on one of two study days (other study day subjects receive placebo.) During Aim 2, given during both of two study days.
DRUGPegvisomant
During Aim 2, given 72 hours prior to one of two study days (Group B subjects only)
DRUGPlacebo
During Aim 1, given on one of two study days (other study day subjects receive sitagliptin.) During Aim 2, given on one of two study days (other study day subjects receive either L-NMMA, pegvisomant, or Exendin 9-39 pending their group assignment)
DRUGL-NMMA
During Aim 2, given during one of two study days (Group A subjects only)
DRUGExendin 9-39
During Aim 2, given during one of two study days (Group C subjects only)
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 to 40 years inclusive * BMI ≤ 25 kg/m2 * For female subjects: Status-post surgical sterilization, or If of child-bearing potential, utilization of a barrier method of birth control following negative serum pregnancy test at screening visit and on every study day
Exclusion criteria
* Smoking * Type 1 or Type 2 Diabetes Mellitus, as defined by a fasting glucose of 126 mg/dL or greater at the time of screening visit or the use of anti-diabetic medication * Hypertension, as defined by an untreated seated systolic blood pressure (SBP) greater than 140 mmHg and/or an untreated diastolic blood pressure (DBP) greater than 90 mmHg at the time of screening visit or the use of anti-hypertensive medication * History of reported or recorded hypoglycemia (plasma glucose \< 70 mg/dL) * Pregnancy and/or Breast-Feeding * Use of any medication other than multivitamin, including use of transdermal as well as oral hormone replacement therapy or use of oral contraceptive therapy * Anemia defined as hematocrit \<35% at screening visit * Cardiovascular or cerebrovascular disease, including history of myocardial infarction, history of congestive heart failure, history of stroke * Pulmonary Hypertension * Abnormal thyroid hormone levels (TSH) at the time of screening visit * Abnormal serum insulin like growth factor-1 (IGF-1) at the time of screening visit * Impaired renal function, defined as estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m\^2 * Impaired hepatic function (alanine or aspartate transaminase \> 2 X upper limit of normal range) * Treatment with an investigational drug in the 1 month preceding the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes | Subjects undergo two study days separated by a washout period. On one study day they will receive sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit every 30 minutes for 3 hours. This was divided into mean arterial pressure to determine forearm vascular resistance. |
| Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes | Forearm blood flow was determined by strain gauge plethysmography. Forearm vascular resistance was then calculated by dividing this into mean arterial pressure. The percent change from baseline was determined at each timepoint. |
| Aim 1: Percent Change From Baseline in Forearm Blood Flow | Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes. | Forearm blood flow was determined by strain gauge plethysmography. The percent change from baseline was determined at each timepoint. |
| Aim 2: Percent Change From Baseline in Forearm Blood Flow | Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes. | Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit. |
| Aim 1: Stimulated Peak Growth Hormone Level | Growth Hormone Level at 30 minutes (i.e. at completion of arginine infusion), 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes | Subjects underwent two study days separated by a washout period. On one study day they will receive sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine (30 grams i.v. over 30 minutes) on each study day. Growth hormone levels were assessed during a 3 hour period following arginine stimulation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | baseline and every 30 minutes until 180 minutes | Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Tissue plasminogen activator activity (tPA) was assessed at each visit. |
| Aim 2: Measurement of Growth Hormone (GH) Levels | baseline and every 30 minutes until 180 minutes | Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Growth hormone secretion following arginine stimulation was assessed at each visit. Growth hormone levels were determined using an assay that is not subject to interference by pegvisomant. |
| Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | baseline and every 30 minutes for 180 minutes | In Aim 1 subjects underwent two study days separated by a washout period. On one study day they received study drug and on another placebo, in a randomized double-blind fashion. Venous blood samples were obtained at each visit. |
Countries
United States
Participant flow
Recruitment details
Healthy Lean Adults are randomized to two cross-over studies (Aim 1 and Aim 2).
Pre-assignment details
In Aim 1, Healthy adults were randomized in a double-blinded cross-over fashion to sitagliptin vs placebo. A minimum 8 week wash-out separated Aims 1 & 2. 23 of the same adults who completed Aim 1 participated in Aim 2. In Aim 2, these adults were divided into three subgroups and randomized to sitagliptin+placebo vs. sitagliptin+antagonist.
Participants by arm
| Arm | Count |
|---|---|
| Participants From All Groups Data was collected as one group | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Aim 1: First Intervention (1 Day) | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Participants From All Groups |
|---|---|
| Age, Continuous | 25 years STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 35 Participants |
| Region of Enrollment United States | 39 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 43 | 0 / 5 | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 7 / 40 | 1 / 43 | 2 / 5 | 0 / 9 | 0 / 8 |
| serious Total, serious adverse events | 0 / 40 | 0 / 43 | 0 / 5 | 0 / 9 | 0 / 8 |
Outcome results
Primary
Aim 1: Percent Change From Baseline in Forearm Blood Flow
Forearm blood flow was determined by strain gauge plethysmography. The percent change from baseline was determined at each timepoint.
Time frame: Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.
Population: Data from all subjects who completed both study days in Aim 1 were analyzed. Subjects represented young, healthy adults without any chronic medical conditions and who did not take any medications. Oral birth control use was not permitted.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aim 1: Sitagliptin,Female Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | 15.9192 percent change from baseline | Standard Deviation 36.11077 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | 0.4835 percent change from baseline | Standard Deviation 19.44436 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | 5.3416 percent change from baseline | Standard Deviation 21.33943 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 23.2248 percent change from baseline | Standard Deviation 40.8397 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 39.9269 percent change from baseline | Standard Deviation 45.00577 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 40.6354 percent change from baseline | Standard Deviation 50.48606 |
| Aim 1: Placebo, Female Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 19.7355 percent change from baseline | Standard Deviation 30.90766 |
| Aim 1: Placebo, Female Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | 1.6458 percent change from baseline | Standard Deviation 19.42502 |
| Aim 1: Placebo, Female Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | 4.9101 percent change from baseline | Standard Deviation 37.42841 |
| Aim 1: Placebo, Female Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 30.0924 percent change from baseline | Standard Deviation 36.51124 |
| Aim 1: Placebo, Female Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 10.3081 percent change from baseline | Standard Deviation 28.3187 |
| Aim 1: Placebo, Female Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | 11.7285 percent change from baseline | Standard Deviation 47.44341 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 21.6011 percent change from baseline | Standard Deviation 42.67343 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | 1.5212 percent change from baseline | Standard Deviation 30.57639 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 16.8489 percent change from baseline | Standard Deviation 24.95539 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | -.0238 percent change from baseline | Standard Deviation 23.86278 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | -2.8869 percent change from baseline | Standard Deviation 25.79685 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 20.1185 percent change from baseline | Standard Deviation 38.89402 |
| Aim 1: Placebo, Male Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 26.1772 percent change from baseline | Standard Deviation 34.7512 |
| Aim 1: Placebo, Male Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | 0.6789 percent change from baseline | Standard Deviation 24.91588 |
| Aim 1: Placebo, Male Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | 13.5358 percent change from baseline | Standard Deviation 37.76659 |
| Aim 1: Placebo, Male Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 9.9379 percent change from baseline | Standard Deviation 28.93967 |
| Aim 1: Placebo, Male Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 15.0944 percent change from baseline | Standard Deviation 34.56449 |
| Aim 1: Placebo, Male Participants | Aim 1: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | 9.2597 percent change from baseline | Standard Deviation 14.60368 |
Primary
Aim 1: Percent Change From Baseline in Forearm Vascular Resistance
Forearm blood flow was determined by strain gauge plethysmography. Forearm vascular resistance was then calculated by dividing this into mean arterial pressure. The percent change from baseline was determined at each timepoint.
Time frame: Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aim 1: Sitagliptin,Female Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | -5.0677 percentage change from baseline | Standard Deviation 18.56794 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | -5.1365 percentage change from baseline | Standard Deviation 16.61555 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | -10.1867 percentage change from baseline | Standard Deviation 22.00489 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | -12.5192 percentage change from baseline | Standard Deviation 31.29272 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -24.1962 percentage change from baseline | Standard Deviation 23.9209 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | -22.4043 percentage change from baseline | Standard Deviation 27.6002 |
| Aim 1: Placebo, Female Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | -16.5358 percentage change from baseline | Standard Deviation 32.22119 |
| Aim 1: Placebo, Female Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | -5.0763 percentage change from baseline | Standard Deviation 26.06546 |
| Aim 1: Placebo, Female Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | -5.3498 percentage change from baseline | Standard Deviation 19.60881 |
| Aim 1: Placebo, Female Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | -1.6694 percentage change from baseline | Standard Deviation 31.84989 |
| Aim 1: Placebo, Female Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | -1.0195 percentage change from baseline | Standard Deviation 22.62776 |
| Aim 1: Placebo, Female Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -11.8335 percentage change from baseline | Standard Deviation 27.88447 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | 6.7355 percentage change from baseline | Standard Deviation 23.96889 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | 1.0144 percentage change from baseline | Standard Deviation 28.50393 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | -10.3674 percentage change from baseline | Standard Deviation 32.22945 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | -11.9609 percentage change from baseline | Standard Deviation 20.50786 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -9.7129 percentage change from baseline | Standard Deviation 30.4028 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | 1.4929 percentage change from baseline | Standard Deviation 21.57596 |
| Aim 1: Placebo, Male Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -7.1590 percentage change from baseline | Standard Deviation 30.41909 |
| Aim 1: Placebo, Male Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | -15.0591 percentage change from baseline | Standard Deviation 25.33331 |
| Aim 1: Placebo, Male Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | 4.6875 percentage change from baseline | Standard Deviation 31.77169 |
| Aim 1: Placebo, Male Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | -2.7449 percentage change from baseline | Standard Deviation 31.52281 |
| Aim 1: Placebo, Male Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | -11.2235 percentage change from baseline | Standard Deviation 13.60628 |
| Aim 1: Placebo, Male Participants | Aim 1: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | -3.8029 percentage change from baseline | Standard Deviation 35.33295 |
Primary
Aim 1: Stimulated Peak Growth Hormone Level
Subjects underwent two study days separated by a washout period. On one study day they will receive sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine (30 grams i.v. over 30 minutes) on each study day. Growth hormone levels were assessed during a 3 hour period following arginine stimulation.
Time frame: Growth Hormone Level at 30 minutes (i.e. at completion of arginine infusion), 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes
Population: Data from all subjects who completed both study days in Aim 1 were analyzed. Subjects represented young, healthy adults without any chronic medical conditions and who did not take any medications. Oral birth control use was not permitted.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aim 1: Sitagliptin,Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 150 minutes | 1.8 ng/ml | Standard Deviation 2.5 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 180 minutes | 0.9 ng/ml | Standard Deviation 0.9 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 60 minutes | 9.4 ng/ml | Standard Deviation 6.4 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 45 minutes | 9.5 ng/ml | Standard Deviation 6.1 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 30 minutes | 5.2 ng/ml | Standard Deviation 4.2 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 120 minutes | 2.7 ng/ml | Standard Deviation 2.1 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 90 minutes | 5.0 ng/ml | Standard Deviation 3.4 |
| Aim 1: Placebo, Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 30 minutes | 3.1 ng/ml | Standard Deviation 3.3 |
| Aim 1: Placebo, Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 180 minutes | 1.3 ng/ml | Standard Deviation 1.9 |
| Aim 1: Placebo, Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 120 minutes | 4.2 ng/ml | Standard Deviation 3.4 |
| Aim 1: Placebo, Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 45 minutes | 6.6 ng/ml | Standard Deviation 5 |
| Aim 1: Placebo, Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 90 minutes | 6.4 ng/ml | Standard Deviation 4.8 |
| Aim 1: Placebo, Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 60 minutes | 7.0 ng/ml | Standard Deviation 6 |
| Aim 1: Placebo, Female Participants | Aim 1: Stimulated Peak Growth Hormone Level | 150 minutes | 2.4 ng/ml | Standard Deviation 2.1 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 180 minutes | 1.0 ng/ml | Standard Deviation 1.9 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 30 minutes | 1.9 ng/ml | Standard Deviation 1.9 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 45 minutes | 3.4 ng/ml | Standard Deviation 3.5 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 60 minutes | 3.0 ng/ml | Standard Deviation 3.6 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 90 minutes | 1.1 ng/ml | Standard Deviation 1 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 120 minutes | 1.5 ng/ml | Standard Deviation 3.1 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 150 minutes | 2.2 ng/ml | Standard Deviation 4.3 |
| Aim 1: Placebo, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 90 minutes | 2.1 ng/ml | Standard Deviation 2 |
| Aim 1: Placebo, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 60 minutes | 3.3 ng/ml | Standard Deviation 2.3 |
| Aim 1: Placebo, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 180 minutes | 1.0 ng/ml | Standard Deviation 1.8 |
| Aim 1: Placebo, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 150 minutes | 1.8 ng/ml | Standard Deviation 3.3 |
| Aim 1: Placebo, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 45 minutes | 3.9 ng/ml | Standard Deviation 3.3 |
| Aim 1: Placebo, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 30 minutes | 2.0 ng/ml | Standard Deviation 2.3 |
| Aim 1: Placebo, Male Participants | Aim 1: Stimulated Peak Growth Hormone Level | 120 minutes | 0.9 ng/ml | Standard Deviation 0.8 |
Primary
Aim 2: Percent Change From Baseline in Forearm Blood Flow
Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit.
Time frame: Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.
Population: 19 of the original 29 females in Aim 1 returned to complete two more study days (Aim 2) in which they received sitagliptin + double-blinded study drug vs. sitagliptin plus placebo in a cross-over study. Three men from Aim 1 also returned to complete two more study days (Aim 2).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aim 1: Sitagliptin,Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | -0.71 percent change from baseline | Standard Error 6.75 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | 3.24 percent change from baseline | Standard Error 10.02 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 14.80 percent change from baseline | Standard Error 15.85 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 16.09 percent change from baseline | Standard Error 13 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | -3.64 percent change from baseline | Standard Error 12.68 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 4.22 percent change from baseline | Standard Error 12.54 |
| Aim 1: Placebo, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | -17.06 percent change from baseline | Standard Error 12.93 |
| Aim 1: Placebo, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 11.26 percent change from baseline | Standard Error 28.45 |
| Aim 1: Placebo, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | -6.35 percent change from baseline | Standard Error 16.6 |
| Aim 1: Placebo, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | -9.34 percent change from baseline | Standard Error 8.6 |
| Aim 1: Placebo, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 9.80 percent change from baseline | Standard Error 18.23 |
| Aim 1: Placebo, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 17.12 percent change from baseline | Standard Error 20.53 |
| Aim 1: Sitagliptin, Male Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | 5.17 percent change from baseline | Standard Error 4.27 |
| Aim 1: Sitagliptin, Male Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 29.24 percent change from baseline | Standard Error 35.21 |
| Aim 1: Sitagliptin, Male Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | 7.05 percent change from baseline | Standard Error 4.06 |
| Aim 1: Sitagliptin, Male Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 26.27 percent change from baseline | Standard Error 13.73 |
| Aim 1: Sitagliptin, Male Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 32.92 percent change from baseline | Standard Error 0.97 |
| Aim 1: Sitagliptin, Male Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | 25.69 percent change from baseline | Standard Error 6.25 |
| Aim 1: Placebo, Male Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 56.26 percent change from baseline | Standard Error 55.06 |
| Aim 1: Placebo, Male Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | 20.32 percent change from baseline | Standard Error 12.83 |
| Aim 1: Placebo, Male Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 65.31 percent change from baseline | Standard Error 80.28 |
| Aim 1: Placebo, Male Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | 14.78 percent change from baseline | Standard Error 14.78 |
| Aim 1: Placebo, Male Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | 4.56 percent change from baseline | Standard Error 0.97 |
| Aim 1: Placebo, Male Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 71.51 percent change from baseline | Standard Error 76 |
| Aim 2: Sitagliptin and Pegvisomant, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | 6.58 percent change from baseline | Standard Error 10.16 |
| Aim 2: Sitagliptin and Pegvisomant, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | 15.64 percent change from baseline | Standard Error 5.06 |
| Aim 2: Sitagliptin and Pegvisomant, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | 36.96 percent change from baseline | Standard Error 14.71 |
| Aim 2: Sitagliptin and Pegvisomant, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 54.10 percent change from baseline | Standard Error 21.87 |
| Aim 2: Sitagliptin and Pegvisomant, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 59.08 percent change from baseline | Standard Error 32.36 |
| Aim 2: Sitagliptin and Pegvisomant, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 51.21 percent change from baseline | Standard Error 26.07 |
| Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | 16.67 percent change from baseline | Standard Error 33.39 |
| Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | 16.10 percent change from baseline | Standard Error 12.79 |
| Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 43.51 percent change from baseline | Standard Error 26.31 |
| Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | 0.39 percent change from baseline | Standard Error 8.93 |
| Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 26.87 percent change from baseline | Standard Error 17.56 |
| Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 41.97 percent change from baseline | Standard Error 31.29 |
| Aim 2: Sitagliptin and Exendin 9-39, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | 2.23 percent change from baseline | Standard Error 8.69 |
| Aim 2: Sitagliptin and Exendin 9-39, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 31.10 percent change from baseline | Standard Error 9.04 |
| Aim 2: Sitagliptin and Exendin 9-39, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | -10.54 percent change from baseline | Standard Error 8.53 |
| Aim 2: Sitagliptin and Exendin 9-39, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 29.48 percent change from baseline | Standard Error 8.22 |
| Aim 2: Sitagliptin and Exendin 9-39, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | -7.33 percent change from baseline | Standard Error 8.66 |
| Aim 2: Sitagliptin and Exendin 9-39, Female Participants | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 30.76 percent change from baseline | Standard Error 8.88 |
| Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 22.24 percent change from baseline | Standard Error 11.14 |
| Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 27.11 percent change from baseline | Standard Error 12.21 |
| Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | 2.08 percent change from baseline | Standard Error 11.6 |
| Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 15.59 percent change from baseline | Standard Error 8.26 |
| Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | -0.98 percent change from baseline | Standard Error 12.08 |
| Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | 6.95 percent change from baseline | Standard Error 9.53 |
| Aim 2: Sitagliptin and Exendin 9-39, Male Participant | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | -7.59 percent change from baseline | — |
| Aim 2: Sitagliptin and Exendin 9-39, Male Participant | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | 5.36 percent change from baseline | — |
| Aim 2: Sitagliptin and Exendin 9-39, Male Participant | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | 54.91 percent change from baseline | — |
| Aim 2: Sitagliptin and Exendin 9-39, Male Participant | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | 9.37 percent change from baseline | — |
| Aim 2: Sitagliptin and Exendin 9-39, Male Participant | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | 16.52 percent change from baseline | — |
| Aim 2: Sitagliptin and Exendin 9-39, Male Participant | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 45.98 percent change from baseline | — |
| Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 120 minutes | -22.00 percent change from baseline | — |
| Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 150 minutes | 1.33 percent change from baseline | — |
| Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 90 minutes | -18.33 percent change from baseline | — |
| Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 180 minutes | -1.67 percent change from baseline | — |
| Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 30 minutes | -22.67 percent change from baseline | — |
| Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Blood Flow | 60 minutes | -13.00 percent change from baseline | — |
Primary
Aim 2: Percent Change From Baseline in Forearm Vascular Resistance
Subjects undergo two study days separated by a washout period. On one study day they will receive sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit every 30 minutes for 3 hours. This was divided into mean arterial pressure to determine forearm vascular resistance.
Time frame: Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes
Population: 19 of the original 29 females who participated in Aim 1 returned to complete an additional two study days (Aim 2) in which they received sitagliptin + double-blinded study drug vs. sitagliptin plus placebo in a cross-over study. Three men from Aim 1 also returned to complete two more study days (Aim 2).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aim 1: Sitagliptin,Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | -8.67 percent change from baseline | Standard Error 9.66 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | -4.89 percent change from baseline | Standard Error 8.93 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | -10.25 percent change from baseline | Standard Error 10.76 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -13.25 percent change from baseline | Standard Error 8.49 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | 8.77 percent change from baseline | Standard Error 17.03 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | 0.99 percent change from baseline | Standard Error 11 |
| Aim 1: Placebo, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | 51.82 percent change from baseline | Standard Error 36.73 |
| Aim 1: Placebo, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | 42.27 percent change from baseline | Standard Error 44.03 |
| Aim 1: Placebo, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | 39.24 percent change from baseline | Standard Error 35.45 |
| Aim 1: Placebo, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | 8.98 percent change from baseline | Standard Error 12.07 |
| Aim 1: Placebo, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | 21.98 percent change from baseline | Standard Error 35.57 |
| Aim 1: Placebo, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | 5.28 percent change from baseline | Standard Error 19.22 |
| Aim 1: Sitagliptin, Male Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | -9.87 percent change from baseline | Standard Error 0.82 |
| Aim 1: Sitagliptin, Male Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | -22.56 percent change from baseline | Standard Error 13.9 |
| Aim 1: Sitagliptin, Male Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | -9.75 percent change from baseline | Standard Error 2.28 |
| Aim 1: Sitagliptin, Male Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -20.62 percent change from baseline | Standard Error 6.34 |
| Aim 1: Sitagliptin, Male Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | -24.81 percent change from baseline | Standard Error 1.18 |
| Aim 1: Sitagliptin, Male Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | -23.34 percent change from baseline | Standard Error 8 |
| Aim 1: Placebo, Male Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | -28.34 percent change from baseline | Standard Error 21.27 |
| Aim 1: Placebo, Male Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | -16.75 percent change from baseline | Standard Error 4.25 |
| Aim 1: Placebo, Male Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | -19.52 percent change from baseline | Standard Error 37.12 |
| Aim 1: Placebo, Male Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | -14.60 percent change from baseline | Standard Error 12.22 |
| Aim 1: Placebo, Male Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | -2.42 percent change from baseline | Standard Error 3.34 |
| Aim 1: Placebo, Male Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -32.11 percent change from baseline | Standard Error 24.34 |
| Aim 2: Sitagliptin and Pegvisomant, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | -4.05 percent change from baseline | Standard Error 10.67 |
| Aim 2: Sitagliptin and Pegvisomant, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | -20.00 percent change from baseline | Standard Error 3.67 |
| Aim 2: Sitagliptin and Pegvisomant, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | -25.28 percent change from baseline | Standard Error 7.02 |
| Aim 2: Sitagliptin and Pegvisomant, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | -32.39 percent change from baseline | Standard Error 8.9 |
| Aim 2: Sitagliptin and Pegvisomant, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -30.12 percent change from baseline | Standard Error 11.1 |
| Aim 2: Sitagliptin and Pegvisomant, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | -25.00 percent change from baseline | Standard Error 11.92 |
| Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | 3.79 percent change from baseline | Standard Error 19.09 |
| Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | -10.97 percent change from baseline | Standard Error 11.64 |
| Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | -17.97 percent change from baseline | Standard Error 15.66 |
| Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | -3.75 percent change from baseline | Standard Error 12.43 |
| Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -14.25 percent change from baseline | Standard Error 13.15 |
| Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | -14.57 percent change from baseline | Standard Error 18.78 |
| Aim 2: Sitagliptin and Exendin 9-39, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | 1.76 percent change from baseline | Standard Error 8.96 |
| Aim 2: Sitagliptin and Exendin 9-39, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | -22.37 percent change from baseline | Standard Error 6.11 |
| Aim 2: Sitagliptin and Exendin 9-39, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | 14.46 percent change from baseline | Standard Error 11.08 |
| Aim 2: Sitagliptin and Exendin 9-39, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -20.92 percent change from baseline | Standard Error 5.3 |
| Aim 2: Sitagliptin and Exendin 9-39, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | 5.30 percent change from baseline | Standard Error 8.19 |
| Aim 2: Sitagliptin and Exendin 9-39, Female Participants | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | -22.58 percent change from baseline | Standard Error 5.82 |
| Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | -13.16 percent change from baseline | Standard Error 10.34 |
| Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | -16.76 percent change from baseline | Standard Error 8.94 |
| Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | 4.82 percent change from baseline | Standard Error 16.53 |
| Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -8.49 percent change from baseline | Standard Error 9.03 |
| Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | 4.53 percent change from baseline | Standard Error 12.62 |
| Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | -4.26 percent change from baseline | Standard Error 7.26 |
| Aim 2: Sitagliptin and Exendin 9-39, Male Participant | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | 0.57 percent change from baseline | — |
| Aim 2: Sitagliptin and Exendin 9-39, Male Participant | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | -14.02 percent change from baseline | — |
| Aim 2: Sitagliptin and Exendin 9-39, Male Participant | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | -34.69 percent change from baseline | — |
| Aim 2: Sitagliptin and Exendin 9-39, Male Participant | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | -11.80 percent change from baseline | — |
| Aim 2: Sitagliptin and Exendin 9-39, Male Participant | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | -16.20 percent change from baseline | — |
| Aim 2: Sitagliptin and Exendin 9-39, Male Participant | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -32.30 percent change from baseline | — |
| Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 120 minutes | 26.68 percent change from baseline | — |
| Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 150 minutes | -1.32 percent change from baseline | — |
| Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 90 minutes | 22.45 percent change from baseline | — |
| Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 180 minutes | 1.69 percent change from baseline | — |
| Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 30 minutes | 27.77 percent change from baseline | — |
| Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group | Aim 2: Percent Change From Baseline in Forearm Vascular Resistance | 60 minutes | 6.73 percent change from baseline | — |
Secondary
Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels
In Aim 1 subjects underwent two study days separated by a washout period. On one study day they received study drug and on another placebo, in a randomized double-blind fashion. Venous blood samples were obtained at each visit.
Time frame: baseline and every 30 minutes for 180 minutes
Population: Data from the first 14 subjects (7 men and 7 women) who completed both study days in Aim 1 were analyzed. We do not report tPA results from the remaining participants as the manufacturer changed the tPA assay standard and results were not comparable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aim 1: Sitagliptin,Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | Baseline prior to Arginine | 0.30 IU/ml | Standard Error 0.05 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 30 minutes | 0.40 IU/ml | Standard Error 0.04 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 45 minutes | 0.43 IU/ml | Standard Error 0.04 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 60 minutes | 0.40 IU/ml | Standard Error 0.06 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 90 minutes | 0.39 IU/ml | Standard Error 0.07 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 120 minutes | 0.40 IU/ml | Standard Error 0.07 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 150 minutes | 0.44 IU/ml | Standard Error 0.04 |
| Aim 1: Sitagliptin,Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 180 minutes | 0.55 IU/ml | Standard Error 0.06 |
| Aim 1: Placebo, Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 120 minutes | 0.35 IU/ml | Standard Error 0.04 |
| Aim 1: Placebo, Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 90 minutes | 0.35 IU/ml | Standard Error 0.06 |
| Aim 1: Placebo, Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 30 minutes | 0.32 IU/ml | Standard Error 0.04 |
| Aim 1: Placebo, Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 180 minutes | 0.50 IU/ml | Standard Error 0.05 |
| Aim 1: Placebo, Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 150 minutes | 0.41 IU/ml | Standard Error 0.04 |
| Aim 1: Placebo, Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 60 minutes | 0.32 IU/ml | Standard Error 0.05 |
| Aim 1: Placebo, Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 45 minutes | 0.35 IU/ml | Standard Error 0.04 |
| Aim 1: Placebo, Female Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | Baseline prior to Arginine | 0.28 IU/ml | Standard Error 0.05 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 150 minutes | 0.42 IU/ml | Standard Error 0.12 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 45 minutes | 0.40 IU/ml | Standard Error 0.1 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 60 minutes | 0.37 IU/ml | Standard Error 0.09 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 90 minutes | 0.34 IU/ml | Standard Error 0.09 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 120 minutes | 0.38 IU/ml | Standard Error 0.12 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 180 minutes | 0.51 IU/ml | Standard Error 0.12 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | Baseline prior to Arginine | 0.44 IU/ml | Standard Error 0.14 |
| Aim 1: Sitagliptin, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 30 minutes | 0.28 IU/ml | Standard Error 0.08 |
| Aim 1: Placebo, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 45 minutes | 0.32 IU/ml | Standard Error 0.08 |
| Aim 1: Placebo, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 60 minutes | 0.34 IU/ml | Standard Error 0.08 |
| Aim 1: Placebo, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 30 minutes | 0.25 IU/ml | Standard Error 0.07 |
| Aim 1: Placebo, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | Baseline prior to Arginine | 0.22 IU/ml | Standard Error 0.07 |
| Aim 1: Placebo, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 90 minutes | 0.27 IU/ml | Standard Error 0.07 |
| Aim 1: Placebo, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 180 minutes | 0.45 IU/ml | Standard Error 0.09 |
| Aim 1: Placebo, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 150 minutes | 0.37 IU/ml | Standard Error 0.08 |
| Aim 1: Placebo, Male Participants | Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 120 minutes | 0.28 IU/ml | Standard Error 0.07 |
Secondary
Aim 2: Measurement of Growth Hormone (GH) Levels
Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Growth hormone secretion following arginine stimulation was assessed at each visit. Growth hormone levels were determined using an assay that is not subject to interference by pegvisomant.
Time frame: baseline and every 30 minutes until 180 minutes
Population: Five of the original 29 women returned for an additional two study days separated by a wash-out period. As pre-specified in the protocol, men did not complete this portion of the study. We did not measure GH levels in participants who received LNMMA or Exendin 9-39 as these drugs are not known to influence GH secretion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aim 1: Sitagliptin,Female Participants | Aim 2: Measurement of Growth Hormone (GH) Levels | 150 minutes | 1.83 ng/mL | Standard Error 0.83 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Measurement of Growth Hormone (GH) Levels | 180 minutes | 1.57 ng/mL | Standard Error 0.82 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Measurement of Growth Hormone (GH) Levels | 30 minutes | 2.99 ng/mL | Standard Error 1.6 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Measurement of Growth Hormone (GH) Levels | 60 minutes | 5.92 ng/mL | Standard Error 2.37 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Measurement of Growth Hormone (GH) Levels | 120 minutes | 4.06 ng/mL | Standard Error 2.18 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Measurement of Growth Hormone (GH) Levels | 90 minutes | 6.05 ng/mL | Standard Error 2.39 |
| Aim 1: Placebo, Female Participants | Aim 2: Measurement of Growth Hormone (GH) Levels | 120 minutes | 6.17 ng/mL | Standard Error 1.21 |
| Aim 1: Placebo, Female Participants | Aim 2: Measurement of Growth Hormone (GH) Levels | 60 minutes | 7.00 ng/mL | Standard Error 2.2 |
| Aim 1: Placebo, Female Participants | Aim 2: Measurement of Growth Hormone (GH) Levels | 180 minutes | 1.77 ng/mL | Standard Error 0.32 |
| Aim 1: Placebo, Female Participants | Aim 2: Measurement of Growth Hormone (GH) Levels | 150 minutes | 4.09 ng/mL | Standard Error 1.33 |
| Aim 1: Placebo, Female Participants | Aim 2: Measurement of Growth Hormone (GH) Levels | 90 minutes | 11.53 ng/mL | Standard Error 4.67 |
| Aim 1: Placebo, Female Participants | Aim 2: Measurement of Growth Hormone (GH) Levels | 30 minutes | 4.27 ng/mL | Standard Error 2.19 |
Secondary
Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels
Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Tissue plasminogen activator activity (tPA) was assessed at each visit.
Time frame: baseline and every 30 minutes until 180 minutes
Population: Five of the original 29 women returned for two more study days separated by a wash-out. As pre-specified in the protocol, men did not complete this portion of the study. We do not report tPA results from participants who received LNMMA and Exendin 9-39 in this table as the manufacturer changed the tPA assay standard and results were not comparable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aim 1: Sitagliptin,Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | Baseline prior to Arginine | 0.24 IU/ml | Standard Error 0.05 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 30 minutes | 0.26 IU/ml | Standard Error 0.04 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 45 minutes | 0.33 IU/ml | Standard Error 0.06 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 60 minutes | 0.27 IU/ml | Standard Error 0.08 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 90 minutes | 0.26 IU/ml | Standard Error 0.07 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 120 minutes | 0.28 IU/ml | Standard Error 0.08 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 150 minutes | 0.31 IU/ml | Standard Error 0.07 |
| Aim 1: Sitagliptin,Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 180 minutes | 0.35 IU/ml | Standard Error 0.06 |
| Aim 1: Placebo, Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 180 minutes | 0.23 IU/ml | Standard Error 0.05 |
| Aim 1: Placebo, Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | Baseline prior to Arginine | 0.10 IU/ml | Standard Error 0.03 |
| Aim 1: Placebo, Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 90 minutes | 0.16 IU/ml | Standard Error 0.05 |
| Aim 1: Placebo, Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 30 minutes | 0.15 IU/ml | Standard Error 0.05 |
| Aim 1: Placebo, Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 150 minutes | 0.20 IU/ml | Standard Error 0.05 |
| Aim 1: Placebo, Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 45 minutes | 0.17 IU/ml | Standard Error 0.06 |
| Aim 1: Placebo, Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 120 minutes | 0.16 IU/ml | Standard Error 0.05 |
| Aim 1: Placebo, Female Participants | Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels | 60 minutes | 0.14 IU/ml | Standard Error 0.04 |