SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies

NCT01744236 · Completed

Last updated 2026-05-28

This clinical trial is studying the effects of incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) on heart rate variability in adults with type 2 diabetes.

Status Completed The study has finished.

Phase Phase 4 Monitors a drug already on the market.

Type Interventional (clinical trial)

Design Randomized, double-blind treatment study

Participants 70 people

Who can join Ages 35–75 · all sexes Healthy volunteers accepted.

Timeline Started 2013-04 · est. completion 2015-08

Where 1 site · Netherlands

What this study is testing ClinicalTrials.gov NCT01744236 ↗

Description as written by the study sponsor.

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.

Treatments tested

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

Main thing measured	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.
Sponsor	Amsterdam UMC, location VUmc
Conditions studied	Type 2 Diabetes
GLP-1 drugs	—

Full protocol, eligibility, and contacts on ClinicalTrials.gov NCT01744236 ↗