SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies

What Was Tested

The trial (phase 4) is built around Exenatide and Liraglutide.

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.

It had seven arms (groups): Liraglutide (main study, long-term intervention) (experimental), Sitagliptin (main study, long-term intervention) (experimental), Placebo (main study, long-term intervention) (placebo comparator), Exenatide (main study, acute intervention) (experimental) and Placebo (main study, acute intervention) (placebo comparator).

This arm (n=20) will receive liraglutide-placebo and sitagliptin-placebo during 12 weeks.

The registry classes the interventions as drug.

More on the Plan

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.

Moreover, in these healthy subjects, the effects of exenatide during L-NMMA infusion will be assessed.

Who Took Part

Enrollment: 70 actual participants took part.

It was open to people of any sex aged from 35 years up to 75 years.

Healthy volunteers could join, not only people with the condition.

Examples of who could join: Age between 35 and 75 years. Females must be post-menopausal (no menses \>1 year). BMI 25 - 40 kg/m2. Signed informed consent.

The full record lists 6 inclusion and 22 exclusion criteria; among the exclusions: 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).

How the Study Was Run

Design: randomized, parallel-group and double-blind.

The participants were allocated by chance, so the Exenatide group and the comparison group should start out alike.

The Exenatide group and the comparison group ran side by side rather than switching.

Blinding on both sides kept the participants and researchers unaware of who received Exenatide.

Those kept unaware of assignments: participant and investigator.

It started in 2013-04 with completion listed for 2015-08.

It ran at 1 site in Netherlands.

Its stated primary purpose is treatment.

What Was Measured

Researchers chose this as the main 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). 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 Glomerular Filtration Rate, measured by the inulin-clearance technique (time frame: 12 weeks). Changes from baseline following 12-week treatment with GLP-1RA or DPP-4i (long-term effects) on pancreatic exocrine function, measured as fecal Elastase-1 (time frame: 12 weeks).

What This Means in Plain Language

Put simply, this is a phase 4, randomized trial of Exenatide and Liraglutide in 70 people.

The trial is marked completed; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Exenatide compound page and the Liraglutide compound page, all human trials.