The purpose of the study is to determine the contribution of endogenous Glucagon-like
peptide 1 (GLP-1) to the postprandial secretion of insulin and glucagon and the incretin
effect in healthy subjects and patients with type 2 diabetes mellitus (T2DM).
Inclusion Criteria:
- male or female (postmenopausal, surgically sterile or using double-barrier method of
contraception) healthy subjects and patients with type 2 diabetes mellitus (T2DM)
- must be able to complete a 1 week wash-out of current anti-diabetic medications
- Age 30-70 years
- HbA1c (Hemoglobin A1c) ≤11% at screening
- Body mass index (BMI) <40 kg/m2
- Patients with type 2 diabetes mellitus (T2DM): Must have a fasting blood glucose of
≤12. 2 mmol/L (240 mg/dL) at screening
- Able to provide written informed consent prior to study participation
- Able to communicate well with the investigator and comply with the requirements of
the study
Exclusion Criteria:
- Patients with type 1 diabetes mellitus (T1DM), diabetes as a result of pancreatic
injury, or secondary forms of diabetes (eg Cushing, acromegaly)
- Need for insulin within the previous 3 months
- Use of Thiazolidinediones in the previous 4 weeks
- Significant concomitant disease or complications of diabetes (i. e. nephropathy,
autonomic dysfunction, orthostasis).
- Treatment with systemic steroids and thyroid hormone (unstable dosage).
- Patients with any history of gastrointestinal surgery, e. g. partial bowel resections,
partial gastric resections, etc.
- Participation in any clinical investigation within 4 weeks prior to dosing or longer
if required by local regulation.
- Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
- Significant illness within the two weeks prior to dosing.
- Past medical history of clinically significant ECG abnormalities or a family history
of a prolonged QT-interval syndrome.
- History of clinically significant drug allergy; history of atopic allergy (asthma,
urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or
drugs similar to the study drug.
- history of major gastrointestinal tract surgery such as gastrectomy,
gastroenterostomy, or bowel resection;
- history or clinical evidence of pancreatic injury or pancreatitis;
- history or presence of impaired renal function as indicated by abnormal creatinine or
urea val-ues or abnormal urinary constituents (e. g., albuminuria);
- evidence of urinary obstruction or difficulty in voiding at screening;
- Polymorphonuclears <1500/µL at inclusion or platelet count < 100,000/μL at screening
and baseline.
- History of immunocompromise.
- Evidence of liver disease as indicated by abnormal transaminases and alkaline
phosphatase exceeding twice the upper limit of the normal range, and serum bilirubin
should not exceed the value of 27 µmol/L (1. 6 mg/dL).
