Antidiabetic Effects of Adding a DPP-4 Inhibitor to Pre-Existing Treatment With an Incretin Mimetic in Patients With T2D

Inclusion Criteria

• Signed & dated written informed consent
• Male & female subjects with a diagnosis of type 2 diabetes mellitus according to ADA criteria at least 4 months prior to screening
• Medical history without major pathology (with the exception of type 2 diabetes) as judged by the investigator
• On a stable regimen of metformin for at least 1 month and liraglutide 1.2 mg for at least 1 week at the time-point of randomisation.
• Age: 25 - 75 years, both inclusive
• Body mass index (BMI): 22 - 40kg/m^2, both inclusive
• HbA1c ≥ 6.5 and ≤ 8.5% (≥ 7.0 and ≤ 8.5% for patients without previous liraglutide treatment)
• Female must be post-menopausal, surgically sterilized or practicing an effective birth control

Exclusion criteria

• Subjects with type 1 diabetes, maturity onset diabetes of the young (MODY) or secondary forms of diabetes such as due to pancreatitis
• Current or previous treatment with insulin therapy (except for treatment at diabetes' diagnosis, within a clinical trial, for surgical procedures or during an acute illness, and no insulin administration within the 6 months before screening)
• Treatment with any hypoglycaemic medication other than metformin and liraglutide within one month prior to screening
• Known of diabetic gastroparesis and / or prokinetic therapy
• Subjects that underwent surgery of the upper gastrointestinal tract
• Women who are pregnant, intending to become pregnant during the study period, currently lactating females, or women of child-bearing potential not using highly effective, medically approved birth control methods
• Any severe medical or surgical history of conditions likely to confound study assessments or study endpoints, for example but not limited to haemoglobinopathies, inflammatory bowel disease, cystic fibrosis, bariatric surgery and/or any surgery shortening the intestine, history of lactose intolerance, lactose- or glucose-galactose-malabsorption
• A suspicion of medullary thyroid cancer or a multiple endocrine neoplasia
• A personal or family history of medullar thyroid cancer or a multiple endocrine neoplasia
• Serious and/or unstable coronary heart disease (unstable angina, myocardial infarction within the preceding 6 months), congestive heart failure of New York Heart Association Class III or worse (severe limitation of physical activity; physical activity of low intensity resulting in fatigue, palpitation, or dyspnoea), second/third degree heart block, superior vena cava syndrome, uncontrolled hypertension, history of congenital QT-syndrome within family, history of stroke (within the preceding 6 months) or serious peripheral vascular disease
• History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (grade 3), left bundle branch block, or asymptomatic sustained ventricular tachycardia are not allowed
• Marked diabetic complications: severe autonomic or sensory neuropathy including previously diagnosed gastroparesis; proliferative retinopathy
• Any respiratory disease leading to respiratory insufficiency and/or depression including but not limited to clinically significant: bronchial asthma, chronic obstructive pulmonary disease, that might impact to the breath test, as judged by the investigator
• Clinically significant vital signs including known bradycardia with pulse rate 450 msec for males or QTc > 470 msec for women
• Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis or coagulation screening tests, as judged by the Investigator
• Moderate or severe renal dysfunction defined as an estimated creatinine clearance (MDRD equation) GFR (glomerular filtration rate) 3x ULN (upper Limit of normal). Isolated mild rise in bilirubin considered to be due to Gilbert's condition is allowed
• Uncontrolled high blood pressure (DBP (diastolic blood pressure) > 95 mmHg and/or SBP (systolic blood pressure) >