Effect of DPP4 Inhibition on Vasoconstriction

Inclusion Criteria

Type 2 Diabetes Mellitus, as defined by one or more of the following,

• Hgb A1C ≥6.5%, or
• Fasting plasma glucose ≥126mg/dL, or
• Two hour plasma glucose ≥200 mg/dL following 75gr oral glucose load

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 some form of birth control and willingness to undergo β-HCG testing prior to drug treatment and on every study day

Exclusion Criteria

• Type 1 diabetes.
• Poorly controlled T2DM, defined as Hgb A1C>8.7%.
• Use of anti-diabetic medications other than metformin.
• 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 any of the following drugs: cisapride, pimozide, terfenadine, astemizol
• Clinically significant gastrointestinal impairment that could interfere with drug absorption
• Cardiovascular disease that would pose risk for the subject to participate in the study, such as: myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy 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] >2 x upper limit of normal range)
• Impaired renal function (eGFR< 60mL/min/1.73m2 as determined by the MDRD equation).
• History or presence of immunological or hematological disorders.
• History of pancreatitis or known pancreatic lesions.
• History of angioedema or cough while taking an ACE inhibitor.
• Hematocrit <35%.
• Treatment with anticoagulants.
• Growth hormone deficiency.
• Diagnosis of asthma requiring use of an 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
• Ongoing tobacco use or recreational drug use.
• 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