Renal Effects of DPP-4 Inhibitor Linagliptin in Type 2 Diabetes

Inclusion Criteria: * Patients with type 2 diabetes (HbA1c: 6.5-9.0% DCCT or 48-75 mmol/mol IFCC) * Metformin monotherapy; using a stable dose for at least 3 months prior to inclusion * Both genders (females must be post-menopausal) * Caucasian * Age: 35-75 years * Body Mass Index: \>25 kg/m2 * All patients with previously diagnosed hypertension should use a RAS-interfering agent (angiotensin converting enzyme inhibitor/angiotensin II receptor blocker) for at least 3 months Exclusion Criteria: * Current / chronic use of the following medication: thiazolidinediones, insulin, glucocorticoids, immune suppressants, antimicrobial agents or chemotherapeutics. Subjects on diuretics will only be excluded when these drugs (e.g. hydrochlorothiazide) cannot be stopped for the duration of the study * Chronic use of NSAIDs will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications. However, no such drugs can be taken within a time-frame of 2 weeks prior to renal-testing * Pregnancy * Frequent occurrence of (confirmed) hypoglycemia (plasma glucose \<3.9 mmol/L) * Estimated Glomerular Filtration Rate \< 60 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation) * Current urinary tract infection and active nephritis * Recent (\<6 months) history of cardiovascular disease, including: acute coronary syndrome, chronic heart failure (New York Heart Association grade II-IV), stroke, transient ischemic neurologic disorder * Complaints compatible with or established gastroparesis and/or neurogenic bladder * Active liver disease * History of or actual pancreatic disease * History of or actual malignancy (except for basal cell carcinoma) * History of or actual severe mental disease * Substance abuse (alcohol: defined as \>4 units/day; smoking/nicotine: defined as daily smoking/use) * Allergy to any of the agents used in the study * Inability to understand the study protocol or give informed consent