Title of project

Effects of antidiabetic medication on glucose distribution, and organ and bone perfusion in patients with type 2 diabetes assessed by modern imaging techniques

Abstract

We aim to investigate the pharmacodynamic effects of antidiabetic treatments. Specifically, we will 1) investigate how glucagon like peptide 1 (GLP-1) receptor agonists, GLP-1:glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonist and sodium glucose co-transporter 2 (SGLT-2) inhibitors affect perfusion and metabolic activity with focus on cardiovascular and renal effecs compared, 2) how these different treatment strategies affect perfusion and metabolic activity of bone tissue. We will also 3) assess the differences between healthy participants and participants with type 2 diabetes at baseline.
Methods: By use of total body PET/CT, we will evaluate whole body, real-time glucose distribution and glucose uptake/metabolic activity in specific tissues/organs (isotope 18Fluor-2-deoxy-2-glucose (18F-FDG)), as well as perfusion and activity of bone tissue (isotope 18Fluor-sodiumfluoride (18F-NaF)).
Population: Participants with type 2 diabetes treated with metformin (n=30), divided into three groups; and a control group of healthy individuals (n=10).
Intervention: Participants with type 2 diabetes will be treated for 12 weeks with either 1) the GLP-1 receptor agonist semaglutide, 2) the GLP-1:GIP receptor co-agonist tirzepatide, or 3) an SGLT-2 inhibitor.
Assessment: Before and after the intervention, each participant will be assessed by an 18F-FDG-PET and a 18F-NaF-PET scan. Healthy participants will only be assessed at baseline.
Outcomes: Primary outcome is change in myocardial glucose uptake before and after treatment. Secondary outcomes include real-time glucose distribution, glucose uptake of specific organs such as intestines, adipose tissue, brain, kidneys, as well as bone metabolic activity and perfusion for all assessed bones before and after treatment, as well as between healthy participants and participants with type 2 diabetes at baseline.
Perspective: The medications studied are widely used but mechanisms underlying their short and long term physiological effects are still uncertain. This study will shed light on the mechanisms of action, contributing to pharmacodynamic insights on which health-care professionals and patients can personalize treatment plans.