NCT04307797

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

A Pilot Study on the Effect of Glucagon and Glucagon-like Peptide-1 Co-agonism on Cardiac Function and Metabolism in Overweight Participants with Type 2 Diabetes (COCONUT)

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Cambridge University Hospitals NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed description

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 positron emission tomography-magnetic resonance imaging (PET-MRI) with fluorine-18-fluorodeoxyglucose (18F-FDG) with placebo (0.9% saline) infusion 2. Cardiac PET-MRI with 18F-FDG with co-infusion of exenatide and glucagon 3. Cardiac PET-MRI with 18F-FDG with infusion of glucagon Part B - Overweight participants with type 2 diabetes will act as their own control and will undergo a series of two imaging studies (in a randomised order), followed by one optional visit as detailed below: 1. 7T Phosphorus (P) 31 magnetic resonance spectroscopy (MRS) (31P-MRS) with placebo (0.9% saline) infusion 2. 7T 31P-MRS with co-infusion of glucagon and exenatide 3 (optional) 7T 31P-MRS with infusion of glucagon Study outcome measures are detailed below

Conditions

• Type 2 Diabetes
• Obesity

Interventions

Type	Name	Description
DRUG	0.9% Sodium-chloride	Part A - 0.9% saline infusion during cardiac PET-MRI scan
DRUG	Exenatide (50ng/min for 30 minutes loading followed by 25ng/min maintenance) and glucagon 12.5ng/kg/min	Part A - exenatide and glucagon infusion during cardiac PET-MRI scan
DRUG	Glucagon 12.5ng/kg/min and 0.9% saline	Part A - Glucagon and 0.9% saline infusion during PET-MRI scan
DRUG	0.9% Sodium-chloride	Part B - 0.9% saline infusion during 7T 31P MRS scan
DRUG	Exenatide (50ng/min for 30 minutes loading followed by 25ng/min maintenance) and glucagon 12.5ng/kg/min	Part B - exenatide and glucagon infusion during 7T 31P MRS scan
DRUG	Glucagon 12.5ng/kg/min	Part B - Glucagon infusion during 7T 31P MRS scan

Timeline

• Start date: 2022-01-18
• Primary completion: 2022-10-07
• Completion: 2022-10-07
• First posted: 2020-03-13
• Last updated: 2024-09-19

Locations

1 site across 1 country: United Kingdom