Vanderbilt Clinical Trials

Age 18 to 80 years old For female subjects the following conditions must be met: Postmenopausal status for at least 1 year, or Status-post surgical sterilization, or If of childbearing potential, utilization of barrier methods of birth control and willingness to undergo urine β-HCG testing prior to drug treatment and on every study day T2DM, as defined by 1 or more of the following at the time of screening visit: - Hgb A1C ≥6.5%, or - Fasting plasma glucose ≥126mg/dL, or - 2-hour plasma glucose ≥200 mg/dL following 75gr oral glucose load Hypertension, as defined by: - Seated SBP ≥130 mm Hg on three occasions documented in medical record, or - Seated DBP ≥80 mm Hg on three occasions documented in medical record, or - Treatment with antihypertensive medications for a minimum of 6 months

• Type 1 diabetes - Poorly controlled T2DM, defined as Hgb A1C>8.7% - Use of anti-diabetic medications other than metformin for at least 12 months prior to initiation of the study - Secondary hypertension - Subjects who have participated in a weight-reduction program during the last 6 months and whose weight has increased or decreased more than 5 kg over the preceding 6 months - Pregnancy - Breast-feeding - Treatment with drugs primarily metabolized through CYP3A4 (e.g. cisapride, pimozide) - Clinically significant gastrointestinal impairment that could interfere with drug absorption - Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy and diastolic dysfunction acceptable), deep vein thrombosis, pulmonary embolism, second- or third-degree AV block, mitral valve stenosis, or hypertrophic cardiomyopathy - Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transaminase [ALT] >3 x upper limit of normal range) - Impaired renal function (eGFR< 50mL/min/1.73m2 as determined by the MDRD equation) - History or presence of immunological or hematological disorders. - History of pancreatitis or know pancreatic lesion - History of angioedema while taking an ACE inhibitor - Hematocrit <35% - Treatment with anticoagulants - Diagnosis of asthma requiring use of inhaled β-2 agonist more than 1 time per week - 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 - Treatment with systemic glucocorticoids within the last 6 months - Treatment with lithium salts - Treatment with any investigational drug in the 1 month preceding the study - Mental conditions rendering the subject unable to understand the nature, scope, or possible consequences of the study - Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study