NCT01744236

SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies

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).

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 70 (actual)
• Sponsor: Amsterdam UMC, location VUmc · Academic / Other
• Sex: All
• Age: 35 Years – 75 Years
• Healthy volunteers: Accepted

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.

Conditions

• Type 2 Diabetes

Interventions

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

Timeline

• Start date: 2013-04-01
• Primary completion: 2015-08-01
• Completion: 2015-08-01
• First posted: 2012-12-06
• Last updated: 2015-12-09

Locations

1 site across 1 country: Netherlands