Effects of Glucagon Like Peptide-1(GLP-1) and Liraglutide on Brain Satiety and Reward Circuits and Feeding Behavior in Diabetes

What Was Tested

This registered not phased trial tested Insulin Glargine and Liraglutide.

The aim of this study is to investigate if endogenous Glucagon Like Peptide -1 (GLP-1) has an effect on brain satiety and reward systems and if there are alterations in obese patients with type 2 diabetes (T2DM).

Secondly, the aim is to investigate whether treatment with a GLP-1 analog, liraglutide, restores these signals in obese patients with type 2 diabetes.

Finally, also the endogenous GLP-1 effects will be investigated in obese individuals before and after gastric bypass surgery on brain satiety and reward systems.

It had three arms (groups): Liraglutide (experimental), Insulin glargine (active comparator) and before start of treatment period (other).

Before start of the treatment period, one day with tests will be performed. During this test a GLP-1 receptor antagonist will be administered In the group with obesity and planned gastric bypass surgery, the GLP-1 receptor agonist will be administered during 1 test before and 1 test after the surgery.

The registry classes the interventions as drug.

More on the Plan

Measurements activation of CNS circuits involved in satiety and reward will be performed using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI).

The second aim will be addressed in cross-over randomized-controlled trial (RCT) in the T2DM patients only.

Patients will be randomly assigned liraglutide vs insulin glargine treatment, during a treatment period of 12 weeks each with a 12-week washout period in between.

The investigators will perform the same fMRI protocol.

Who Took Part

50 actual participants took part.

It was open to people of any sex aged from 18 years up to 65 years.

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

Examples of who could join: For the healthy, lean individuals:. Age 18-65 years. Women: post menopausal (excluding possible menstruation cycle effects). Body-mass index (BMI) of \<25 kg/m2,. Normal fasting and 2h post load glucose as ascertained during a 75-g oral glucose tolerance test (OGTT) (34).

The full record lists 21 inclusion and 25 exclusion criteria; among the exclusions: GLP-1 based therapies, thiazolidinediones, sulphonylurea or insulin within 3 months before screening; weight-lowering agents within 3 months before screening; congestive heart failure (nyha ii-iv).

How the Study Was Run

The set-up was randomized, crossover and open-label.

Because people in this Insulin Glargine study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

In the crossover set-up each of the participants took both Insulin Glargine and the comparison in turn, acting as their own control.

Nothing was hidden in this open-label Insulin Glargine study: the participants and staff both knew the treatment.

It started in 2011-10 with completion listed for 2015-01.

It ran at 1 site in Netherlands.

What Was Measured

Primary outcome: food-stimuli related neuronal activity in reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%) (time frame: approximately 3 years).

It also tracked 9 secondary outcomes, for example GLP-1 analog treatment related changes in obese patients with type 2 diabetes in self-reported hunger, satiety, fullness, GLP-1 analog treatment related changes in obese patients with type 2 diabetes in basal metabolic rate and post-prandial energy expenditure, GLP-1 analog treatment related changes in obese patients with type 2 diabetes in microvascular function and vasomotion, GLP-1 analog treatment related changes in obese patients with type 2 diabetes in cardiovascular autonomic nervous balance, GLP-1 analog treatment related changes in obese patients with type 2 diabetes in concomitant changes in metabolic and humoral markers and GLP-1 analog treatment related changes in obese patients with type 2 diabetes in resting state brain activity networks.

What This Means in Plain Language

Put simply, this is a not phased, randomized trial of Insulin Glargine and Liraglutide in 50 people.

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

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