Eligibility Details:
Inclusion Criteria:
1. Men and women,
2. Age 21 to 50 years, and
3. Pre-diabetes as defined by
1. Fasting plasma glucose 100-125 mg/dL, or
2. Two-hour plasma glucose 140-199 mg/dL, or
3. HbA1c 5.7-6.4%
4. BMI ≥ 30 kg/m2, inclusive
5. For female subjects, the following conditions must be met:
1. Postmenopausal status for at least one year, or
2. Status-post surgical sterilization, or
3. If of childbearing potential, utilization of adequate birth control and
willingness to undergo serum β-hcg testing prior to drug treatment and on every
study day.
Exclusion Criteria:
1. Diabetes type 1 or type 2, as defined by a fasting plasma glucose of 126 mg/dL or
greater, a two-hour plasma glucose of 200 mg/dL or greater, a HbA1c >6.4%, or the use
of anti-diabetic medication
2. Subjects who have participated in a weight-reduction program during the last six month
or whose weight has increased or decreased more than two kg over the preceding six
months
3. Resistant hypertension, defined as hypertension requiring the administration of more
than three anti-hypertensive agents including a diuretic to achieve control
4. Use of spironolactone
5. Pregnancy or breast-feeding
6. Any history of smoking
7. Any history of cancer including skin cancer, any history of a precancerous lesion,
abnormal PSA, or lack of screening adherent to American Cancer Society Guidelines for
the Early Detection of Cancer
8. Cardiovascular disease such as myocardial infarction within six months prior to
enrollment, presence of angina pectoris, significant arrhythmia, congestive heart
failure (left ventricular hypertrophy acceptable), deep-vein thrombosis, pulmonary
embolism, second- or third-degree heart block, mitral valve stenosis, aortic stenosis,
or hypertrophic cardiomyopathy
9. Abnormal corrected QT interval on screening ECG (QTc).
10. Treatment with anticoagulants
11. History of serious neurologic disease such as cerebral hemorrhage, stroke, or
transient ischemic attack
12. History or presence of immunological or hematological disorders
13. Diagnosis of asthma requiring regular inhaler use
14. Clinically significant gastrointestinal impairment that could interfere with drug
absorption
15. Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino
transaminase [ALT] >3.0 x upper limit of normal range)
16. History of gastrointestinal bleed
17. Estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2 or with an
albumin-to-creatinine ratio (UACR) >300µg/mg, where eGFR is determined by the
four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum
creatinine is expressed in mg/dL and age in years: eGFR (mL/min/1.73m2)=186 •
Scr-1.154 • age-0.203 • (1.212 if black) • (0.742 if female)
18. Hematocrit <35%
19. Any underlying or acute disease requiring regular medication which could possibly pose
a threat to the subject or make implementation of the protocol or interpretation of
the study results difficult
20. Treatment with chronic systemic glucocorticoid therapy
21. Treatment with lithium salts
22. History of alcohol or drug abuse
23. Treatment with any investigational drug in the month preceding the study
24. Mental conditions rendering a subject unable to understand the nature, scope, and
possible consequences of the study
25. Inability to comply with the protocol, e.g., uncooperative attitude, inability to
return for follow-up visits, and unlikelihood of completing the study
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-no
