Antagonist of the Glucagon-like Peptide 2 (GLP-2) Receptor
Phase: NA
Conditions: Healthy
Sponsor: University of Copenhagen

 
 
06.01.25 
 
 
Antagonist of the glucagon-like peptide 2 (GLP-2) 
receptor 
 
Department of Biomedical Sciences, 
University of Copenhagen 
 
H-24000668 
Date: 06/01/25 
 
 

 
 
06.01.25 
Title: Antagonist of the glucagon-like peptide 2 (GLP-2) receptor 
 
Approved ethical committee ID: H-24000668 
 
Project Group: 
Lærke Smidt Gasbjerg, MD, PhD (PI) 
Sophie Woge Nielsen, MD, PhD-student 
Lotte Alstrup, B.A. Science 
Andreas Holst Lange, Med.-student 
Rasmus Syberg Rasmussen, cand.scient. 
Ulrik Bjørn Andersen, MD 
Bryan Haddock, cand. scient., PhD 
Mark Bitsch Vestergård, cand.scient. PhD 
Professor Jens Juul Holst, MD, DMSc 
Professor Henrik Bo Wiberg Larsson, MD, DMSc 
Professor Mette Marie Rosenkilde, MD, PhD 
 
Background:  
Previous studies have shown that GLP-2 increase abdominal blood flow to the intestines. The studies 
that reveal this effect are built on results of exogenous distributed GLP-2 and have not investigated 
the endogenous effects of GLP-2. We have previously performed a single study in healthy males with 
the use of flow sensitive magnetic resonance imaging (MRI) where supraphysiological doses of GLP-
2 injections greatly increased the blood flow in the superior mesenteric artery and portal vein but 
there were surprisingly no changes after intake of oral glucose. In this study we investigate if 
physiological doses of GLP-2 will increase the blood flow to the intestines and if different doses of 
the GLP-2 receptor antagonist (GLP-2(3-33)) can alter these flow changes in humans of both genders.  
 
Aim: We aim to determine the right dose of the GLP-2-receptor antagonist to use in physiological 
research in healthy humans. We hope to be able to achieve the maximal blocking of the GLP-2 
receptor possible and at the same time reduce expenses and infusion volume for the participants in 
future studies. We thereby hope to characterize the use of the GLP-2 receptor antagonist GLP-2(3-
33) as an essential tool in research of the role of the human GLP-2 receptor in bone metabolism and 
nutrient uptake in the future.   
 
Hypothesis: The hypothesis of this study is that the GLP-2(3-33) can block the effects of GLP-2 on 
the blood flow to the superior mesenteric artery and the portal vein. 
 
Design: 
Randomized, placebo controlled, crossover, single blind design in 10 healthy participants.  
 
Baseline information: 
A description of the baseline measured will be presented in a table, including the following measures: 
Age, Weight, Height, BMI, Hemoglobin, Leucocytes, Vitamin D, Fasting glucose, HbA1c, Sex, and 
Blood pressure. The data will be presented in Median and range. 
 
 
Statistical analysis and graphs: 

 
 
06.01.25 
The flow data is analyzed in Rs studio by a linear mixed model, that pairs the data, and compared the 
interventions after steady state of the infusion of GLP-2(3-33) antagonist. The primary statistical 
analysis will be done between the interventions: Physiological dose of GLP-2 injection and highest 
dose of GLP-2-antagonist infusion + GLP-2 injection and placebo infusion. Furthermore, the data 
will be presented in GraphPad Prism 10. A data table will present the flow measurements of each 
intervention, including mean and 95% confidence intervals 
 
Criteria: 
Inclusion  
1) Age 18-70 years  
2) BMI 19-28 kg/m2 
Exclusion  
3) Chronic illness that affects the cardiovascular system or gastrointestinal tract 
4) Treatment with medicine or supplements that cannot be paused for 12 hours 
5) Intake of above 14 alcoholic drinks per week or substance abuse 
6) Liver enzymes (ALAT) above 2 times normal values 
7) Decreased kidney function (eGFR below 90 or creatinine levels over reference value) 
8) Low blood percentage (hemoglobin below reference value) 
9) Any condition or disease that the persons responsible for the study find would interfere with 
the participation of the study.  
 
Methods and outcomes: Phase-contrast magnetic resonance imaging (PC-MRI) is used to calculate 
blood flow in the blood vessels: superior mesenteric artery, portal vein, celiac trunk and hepatic artery 
during the infusion of either saline or GLP-2(3-33) receptor antagonist and injection of GLP-2.  
The main outcome of the study is blood flow in superior mesenteric artery. On each study day, 8 
MRI scans are performed (-32 min to 60 min after start of infusion) and four blood samples are taken. 
Blood glucose is measured bedside on whole blood. The blood samples collected are kept for analysis 
of GLP-2(1-33), GLP(3-33) and markers of bone metabolism.  
 
 
Adverse event: 
All adverse events (AEs) or serious adverse event (SAE) are reported throughout the whole study 
period, any adverse event reported will be informed to the ethical committee responsible for the 
study. All AEs including local and systemic reactions not meeting the criteria for SAEs will be 
captured on the appropriate case report form. Information to be collected includes event description, 
time of onset, qualified medical professional’s assessment of severity, relationship to study product 
(assessed only by those with the training and authority to make a diagnosis), and time of 
resolution/stabilization of the event. All AEs occurring while on study must be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution.