Mifepristone Effects on Glucose Intolerance in Obese/Overweight Adults

Exclusion Criteria

• •1. Pregnancy and lactation
• •2. Diabetes requiring pharmacologic treatment. Diagnosis of diabetes will be based on the 2011 American Diabetes Association guidelines: HbA1C greater than or equal to 6.5%, fasting plasma glucose greater than or equal to 126 mg/dl, 2-hour glucose greater than or equal to 200 mg/dl during an OGTT, or a random blood glucose greater than or equal to 200 mg/dl along with classic symptoms of hyperglycemia (34)
• •3. Uncontrolled hypertension (blood pressure greater than or equal to 180/110 mmHg)
• •4. Current unstable medical conditions including clinically significant impaired cardiac function (Stage III and IV Cardiac failure), cardiac ischemia, severe respiratory insufficiency requiring oxygen therapy as assessed on history and/or physical exam
• •5. Liver function tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST) more than 3-times the upper normal limit
• •6. Severe renal impairment (creatinine clearance \< 30 ml/min)
• •7. Evidence of human immunodeficiency virus (HIV) based on history and physical examination and/or known positive HIV antibodies
• •8. Evidence of hepatitis C based on history and physical examination and/or known positive hepatitis C (HCV) antibody
• •9. History of hemorrhagic disorders or on anticoagulants
• •10. History of endometrial cancer, endometrial hyperplasia, unexplained vaginal bleeding, or endometrial thickness greater than 6 mm
• •11. Change in dose of lipid-lowering medications (including 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG Co-A) inhibitors , fibrates, niacin, ezetimibe, and over-the-counter fish oil supplements) within one month of study entry and during the study period
• •12. Current administration of medications known to be strong CYP3A4 inhibitors including ketoconazole, itraconazole, and erythromycin
• •13. Use of herbal supplements or grapefruit juice within 14 days of study drug initiation
• •14. Use of medications or dietary supplements that inhibit or induce CYP3A4 activity within 14 days of study drug initiation
• •15. Use of oral, injectable, or inhaled glucocorticoids or megestrol in the past six months
• •16. Use of estrogen-containing hormone therapy
• •17. Potential pseudocushing's states: depression or intake of \> 2 alcoholic drinks a day. Subjects will be screened for depression using the well-validated physician health questionnaire-9 (PHQ-9) with a score cut-off of greater than or equal to 10 for moderate depression (35).
• •18. Subjects who are actively dieting or are in a weight loss program
• •19. Midnight salivary cortisol \> 100 ng/dl on two separate occasions
• •20. Untreated thyroid dysfunction (thyroid stimulating hormone and Free thyroxine (FT4) not within normal range). If abnormal on screening labs, they will be repeated to confirm that not due to lab error or non-thyroidal illness.
• •21. Moderate to severe anemia (hemoglobin \< 10 g/dl)
• •22. Blood donation of more than 500 ml within one month prior to study enrollment
• •23. Subjects with a prolonged corrected Q-T interval (QTc) on electrocardiogram
• •24. Unable to give informed consent