SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      GLP-1 receptors are present in most organ systems of the human body, and pharmacological
      interventions enhancing GLP-1 activity may influence the function of these organs. The use of
      GLP-1 receptor agonists (GLP-1RA) and DPP-4 inhibitors (DPP-4i) has been associated with an
      increased heart rate, acute pancreatitis and acute renal failure. To date, studies in humans
      detailing the effects of these drugs on these organ systems, biological processes and
      underlying mechanisms, which could explain these associations, are lacking.

      Therefore, as part of the EU-FP7 SAFEGUARD program, the present study will aim to detail the
      (mechanisms underlying the) actions of GLP-1RA and DPP-4i on the cardiovascular, renal and
      gastrointestinal system in healthy obese subjects and patients with T2DM.

      In the main study, sixty patients with type 2 diabetes will undergo two interventions within
      the same protocol in order to assess changes in the outcome parameters:

        -  acute study = acute infusion with exenatide or placebo (to assess the cardiovascular and
           renal effects)

        -  long-term study = 12 weeks of treatment with liraglutide, sitagliptin or placebo (to
           assess the cardiovascular, renal and gastrointestinal effects)

      In a substudy (termed 'acute MRI study'), twelve patients with type 2 diabetes will undergo
      an additional acute intervention study with exenatide (to assess the pancreatic effects)

      In a substudy (termed 'pilot-study'), ten healthy obese subjects will undergo a similar acute
      study like the patients with type 2 diabetes (to assess the cardiovascular and renal
      effects). Moreover, in these healthy subjects, the effects of exenatide during L-NMMA
      infusion will be assessed.
    

Intervention name(s): Liraglutide; Sitagliptin; Exenatide; Liraglutide placebo; Sitagliptin placebo; Exenatide placebo; L-NMMA
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Liraglutide will be started with a titration period of 2 weeks (week 1: 0.6mg once daily and week 2: 1.2mg once daily). If liraglutide is well tolerated it will be continued for 10 more weeks in a dosage of 1.8mg once daily.; Sitagliptin 100mg will be given once daily for 12 weeks.; Exenatide will be administered intravenously with a loading dose of 50ng/min for 30 minutes, followed by a maintenance dose of 25ng/min during the rest of the tests; Liraglutide-placebo will be started with a titration period of 2 weeks (week 1: 0.6mg once daily and week 2: 1.2mg once daily). It will be continued for 10 more weeks in a dosage of 1.8mg once daily.; Sitagliptin-placebo be given once daily for 12 weeks.; Exenatide-placebo (saline) will be administered intravenously
Intervention MeSH terms: Sitagliptin Phosphate; Liraglutide; Exenatide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: GLP-1 Receptor Agonists, DPP-4 inhibitors