The purpose of this study is to assess the effects of incretin-based antidiabetic therapies (DPP-4 inhibitors and GLP-1 agonists) on cardiovascular, gastrointestinal and renal system and to detail the mechanisms underlying their action in these systems.

Inclusion Criteria:

• Type 2 diabetes mellitus
• Metformin monotherapy - stable dose during last 3 months
• HbA1C 48-75 mmol/mol (IFCC)
• BMI 25-40 kg/m2
• Age 35-70 years (women postmenopausal)
• Use of ACE inhibitors or ATII receptor blockers for at least 3 months before enrollment

Exclusion Criteria:

• eGFR<30 ml/min/1.73m2 (MDRD)
• Treatment with incretin mimetics during 3 months before enrollment
• Chronic insulin therapy
• Chronic use of loop diuretics, glucocorticoids, NSAID, immune suppressants, antimicrobial agents, chemotherapeutics, bile acid sequestrants (colestyramin, colesevelam)
• History of pancreatic disease or impaired pancreatic function (defined as the need to use pancreatic enzymes)
• Active liver disease or a 3-fold elevation of liver transaminases (ALT, AST)
• Active malignancy
• History of severe cardiovascular disease including acute coronary syndrome, stroke or transient ischemic neurologic disorder during previous 6 months, atrial fibrillation or other arrhythmia requiring chronic antiarrhythmic medication, chronic heart failure (New York Heart Association grade III/IV)
• History of alcohol abuse, defined as >4 units of alcohol/day (32 g or 40 ml of 100% alcohol)
• History of allergy for GLP-1 receptor agonists or DPP-4 inhibitors
• Any disease that could interfere with study procedures (e.g. decreased mobility, mental incapacity)
• Inability to give informed consent