SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies

Sponsor
Amsterdam UMC, location VUmc
Study ID
NCT01744236
Phase
PHASE4
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
35 Years - 75 Years
Healthy Volunteers
Accepted

Interventions

  • Liraglutide — DRUG
    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 — DRUG
    Sitagliptin 100mg will be given once daily for 12 weeks.
  • Exenatide — DRUG
    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 — DRUG
    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 — DRUG
    Sitagliptin-placebo be given once daily for 12 weeks.
  • Exenatide placebo — DRUG
    Exenatide-placebo (saline) will be administered intravenously
  • L-NMMA — DRUG

Study Details

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.

Key Dates

Start date
Apr 30, 2013
Status verified
Dec 2015
Primary completion
Aug 31, 2015
Completion
Aug 31, 2015

Study Design

Enrollment
70 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Liraglutide (main study, long-term intervention)
    This arm (n=20) will receive liraglutide 1.8mg and sitagliptin-placebo during 12 weeks
  • Experimental: Sitagliptin (main study, long-term intervention)
    This arm (n=20) will receive sitagliptin 100mg and liraglutide-placebo during 12 weeks
  • Placebo Comparator: Placebo (main study, long-term intervention)
    This arm (n=20) will receive liraglutide-placebo and sitagliptin-placebo during 12 weeks
  • Experimental: Exenatide (main study, acute intervention)
    Prior to the 12-week intervention study, a GLP-1 receptor agonist (exenatide) will be administered intravenously (n=30).
  • Placebo Comparator: Placebo (main study, acute intervention)
    Prior to the 12-week intervention study, placebo will be administered intravenously (n=30).
  • Other: Acute MRI intervention study
    In a subset of 12 patients with type 2 diabetes, a crossover trial with acute infusion of exenatide and placebo is performed. This is done prior to the 12-week intervention study.
  • Other: Pilot-study
    In 10 healthy obese subjects, a crossover trial with acute infusion of exenatide, placebo and L-NMMA is performed.

Primary Outcome Measure

Changes from baseline following infusion of GLP-1RA (acute effects) and the changes from baseline following 12-week treatment with GLP-1RA or DPP-4i (long-term effects) on resting heart rate variability, as derived from electrocardiographic measurements. [ Time Frame: 12 weeks ]

Related Studies