SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies

Inclusion Criteria: * Age between 35 and 75 years. * Females must be post-menopausal (no menses \>1 year). * Type 2 diabetes (HbA1c 6.5-9% DCCT or 48-75 mmol/mol IFCC), who are being treated with a stable dose of oral antihyperglycemic agents (either metformin alone, SU alone or a combination of metformin and SU) for at least 3 months prior to inclusion. * BMI 25 - 40 kg/m2 * Caucasian * Signed informed consent Exclusion Criteria: * GFR \< 60 mL/min/1.73m2 * Current / chronic use of the following medication: thiazolidinediones, GLP-1RA, DPP-4i, glucocorticoids, NSAIDs, insulin, antimicrobial agents, chemotherapeutics or immune suppressants. Subjects on diuretics will only be excluded when these drugs (e.g. hydrochlorothiazide) cannot be stopped for the duration of the study. * History of or actual pancreatic disease or impaired pancreatic exocrine function * Active liver disease * History of or actual malignancy (with the exception of basal cell carcinoma) * Current urinary tract infection and active nephritis * Recent (\<6 months) history of cardiovascular disease, including acute coronary syndrome, stroke, transient ischemic neurologic disorder or chronic heart failure (New York Heart Association grade II-IV) * Current atrial fibrillation * Chronic infectious or auto-immune disease * Substance and/or alcohol abuse * History of allergy/hypersensitivity to any of the test agents * Complaints compatible with or established gastroparesis and/or neurogenic bladder * Any condition that has been recognized as a contra-indication for the use of GLP-1RA and DPP-4i, as listed in the respective SPCs * History of or actual (severe) mental illness * Inability to understand the study protocol and/or inability to give informed consent * History of claustrophobia or presence of metal objects/implants (because of MRI protocol) For the preceding Pilot study, we will include: * Males * Age between 18 and 50 years * BMI 25 - 40 kg/m2 * Caucasian The exclusion criteria for the preceding pilot study are similar to the exclusion criteria of the main study, with the additions of: * Subjects with a fasting plasma glucose ≥5.6 mmol/L, a 2-hour glucose of ≥7.8 mmol/L after a 75-grams oral glucose tolerance test, or a HbA1c of ≥6.5% * Subjects using any kind of medication