SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies

• Status: Completed
• Trial end date: 2015-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The aim of this study is to detail the (mechanisms underlying the) actions of the GLP-1 receptor agonists and DPP-4 inhibitors on the cardiovascular, renal and gastrointestinal systems in patients with Type 2 Diabetes Mellitus.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: VU University Medical Center
• Collaborator: EU FP7: SAFEGUARD consortium
• Treatments: Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Glucagon-Like Peptide 1; Liraglutide; Sitagliptin Phosphate

Criteria

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