Effect of Glucagon and Glucagon-like Peptide-1 Co-agonism on Cardiac Function and Metabolism in Overweight Participants with Type 2 Diabetes

What Was Tested

This registered phase 4 trial tested Exenatide and Glucagon.

The study seeks to explore the cardiovascular effects of co-agonism at the glucagon and (glucagon-like peptide-1) GLP-1 receptor.

Glucagon and exenatide will be intravenously infused into participants with type 2 diabetes (T2DM).

Overall, the aim of the study is to further the investigator's understanding on the role these endogenous substances have on normal cardiac physiology, myocardial energetics and myocardial glucose uptake through a series of PET and MRI imaging studies.

The registry classes the interventions as drug.

More on the Plan

This is a single-centre, single-blinded pilot study designed to understand the role the GLP-1 receptor agonist, exenatide, and glucagon receptor co-agonism has on normal cardiac physiology, myocardial energetics and myocardial glucose utilisation.

Part A - Overweight participants with type 2 diabetes will act as their own control and will undergo a series of three imaging studies (in a randomised order) as detailed below: 1.

Cardiac PET-MRI with 18F-FDG with co-infusion of exenatide and glucagon 3.

Who Took Part

10 actual participants took part.

It was open to people of any sex aged from 18 years up to 99 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Written informed consent to participate. Aged \>18 years. Clinical diagnosis of T2DM, either diet controlled or treated with metformin (to be withheld on the morning of the imaging visit).

The full record lists 5 inclusion and 13 exclusion criteria; among the exclusions: females of childbearing potential (part a only) / current pregnancy (all parts); sustained hypertension (sustained bp \>160/100mmhg) or hypotension (systolic bp below 90 mmhg); implanted heart pacemaker or implantable cardioverter defibrillator (icd).

How the Study Was Run

It was run as a randomized, single-group and single-blind study.

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

Everyone received the same intervention, so there was no separate comparison group inside the trial.

Those kept unaware of assignments: participant.

It started in 2022-01-18 with completion listed for 2022-10-07.

It ran at 1 site in United Kingdom.

Its stated primary purpose is basic science.

What Was Measured

Primary outcome: Part A - Myocardial glucose uptake (time frame: Comparison between scans over a maximum period of 16 weeks). Part A - Global longitudinal strain / global circumferential strain / global radial strain (time frame: Comparison between scans over a maximum period of 16 weeks). Part A - Ejection fraction (time frame: Comparison between scans over a maximum period of 16 weeks).

It also tracked 14 secondary outcomes, for example Part A - End systolic/diastolic ventricular/atrial volumes, Part A - Radial strain, Part A - Global systolic/diastolic longitudinal/circumferential/radial strain rate, Part A - Relationship between early and late filling (from mitral flow), Part A/B - Heart rate and Part A/B - Blood pressure.

What This Means in Plain Language

Put simply, this is a phase 4, randomized trial of Exenatide and Glucagon in 10 people.

Its size is small, so on its own it can only give an early look.

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 Glucagon compound page, all human trials.