The Effect of GLP-1 Receptor Activation on Central Reward and Satiety in Obesity and Diabetes

What Was Tested

This registered not phased trial tested Exenatide.

Glucagon-like peptide 1 (GLP-1) based therapies, such as exenatide, are already successfully employed in the treatment of Type 2 Diabetes (T2DM).

The investigators hypothesize that it affects central reward and satiety circuits and that this may contribute to the weight loss.

It had three arms (groups): exenatide (experimental), exenatide + exendin (9-39) (experimental) and saline (placebo comparator).

Saline infusion, with the same infusion speed.

The registry classes the interventions as drug.

More on the Plan

To tease out concomitant postprandial metabolic and hormonal influences, measurements will be performed during a somatostatin pancreatic clamp with replacement of basal insulin, glucagon and growth hormone.

Finally, to correlate changes in brain activity with subsequent feeding behavior, the investigators will measure food intake, self-reported hunger, satiety and mood, during a choice-buffet after the scanning.

Expected Results This project will gain insight into (CNS) mechanisms underlying the observed effects of the GLP-1 receptor agonist exenatide on food intake and body weight in obese, diabetic and healthy lean individuals.

Who Took Part

48 actual participants took part.

It was open to people of any sex aged from 18 years up to 70 years.

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

Examples of who could join: Age 18-70 years. Men and women. For women, only postmenopausal women (as ascertained by serum FSH) will be included in order to avoid variations related to the menstrual cycle. To promote comparability and to overcome the interference of lateralization, only right-handed persons will be included. Body-mass index (BMI) of \<25 kg/m2. Normal fasting and 2-h postload glucose as ascertained during a 75-g oral glucose tolerance test (OGTT).

The full record lists 13 inclusion and 21 exclusion criteria; among the exclusions: congestive heart failure (nyha ii-iv); a history of gastrointestinal disorders, including gastroparesis, pancreatitis and cholelithiasis; neurological illness.

How the Study Was Run

The set-up was randomized, crossover and single-blind.

Because people in this Exenatide 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 Exenatide and the comparison in turn, acting as their own control.

In this single-blind Exenatide study one party knew the assignments and the other did not.

Those kept unaware of assignments: participant.

It started in 2011-09 with completion listed for 2013-10.

It ran at 1 site in Netherlands.

What Was Measured

Primary outcome: Differences in neuronal activity in CNS reward and satiety circuits (time frame: 1 hour).

It also tracked 2 secondary outcomes, for example Feeding behavior and Self-reported hunger.

What This Means in Plain Language

Put simply, this is a not phased, randomized trial of Exenatide in 48 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, all human trials.