Effect of Chronic ACE and DPP4 Inhibition on Blood Pressure

Inclusion Criteria

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

Exclusion Criteria

• 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