A phase IV, randomized, double-blind, placebo-controlled, parallel-group trial to assess the effect of 12-week treatment with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide or dipeptidyl peptidase-4 inhibitor (DPP-4i) sitagliptin on the cardiovascular, renal and gastrointestinal system in insulin-naïve patients with type 2 diabetes (T2DM).

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 70

Inclusion Criteria

- Both genders
-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;For the preceding pilot-study:
- Males
- Age between 18 and 50 years
- BMI 25 * 40 kg/m2
- Caucasian

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 (defined as needed use of pancreatic enzymes)
- Active liver disease or a 3-fold elevation of liver enzymes (AST / ALT) at screening
- 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, defined as >4 units alcohol/day (because of risk of pancreatitis)
- History of allergy/hypersensitivity to GLP-1RA, DPP-4i, inulin, para-aminohippuric acid, acetaminophen, secretin, MRI contrast agent or latex (component of PAH).
- 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:
Similar to the exclusion criteria for 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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Cardiovascular part: resting heart rate variability<br /><br><br /><br>Renal part: glomerular filtration rate.<br /><br><br /><br>Gastrointestinal part: fecal elastase-1.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Cardiovascular part:<br /><br>- Blood pressure<br /><br>- Heart rate<br /><br>- Hemodynamic variables<br /><br>- Autonomic nervous system (ANS) function<br /><br>- Microvascular function<br /><br>- Arterial stiffness<br /><br>- Plasma lipid spectrum<br /><br>- Glycemic variables<br /><br>- Body anthropometrics and body fat content<br /><br><br /><br>Renal part:<br /><br>- Renal plasma flow<br /><br>- Renal tubular function<br /><br>- Renal damage parameters<br /><br><br /><br>Gastrointestinal part:<br /><br>- Pancreatic exocrine function/structure<br /><br>- Plasma pancreatic enzymes<br /><br>- Gallbladder motility<br /><br>- Liver enzymes<br /><br>- Hepatic function<br /><br>- Hepatic steatosis<br /><br>- Gastric emptying speed</p><br>