Imaging Pituitary ActiVation by Exendin (iPAVE)

The main goal is the comparison of pituitary uptake of Ga-68-NODAGA-exendin-4 in patients with and without adequate response (based on HbA1c or weight loss) to GLP-1R agonist treatment.

The prevalence of type 2 diabetes (T2D) is increasing and a better understanding of the mechanisms of T2D becomes increasingly important. The glucagon-like peptide 1 receptor agonists (GLP-1RA), such as exendin, can be used as potent antidiabetic drugs for treatment of T2D. Not all patients with T2D respond to treatment with GLP-1RA and some even respond with contradictory effects, but the underlying mechanism for this observation remains unclear. Interestingly, uptake of an exendin-based radiotracer was observed in the pituitary gland in diabetes patients. In this study, the effect of GLP-1RA on the HPA axis will be further studied for an improved understanding of the mechanisms and contradictory treatment responses. Patient data will be obtained and will consist of metabolic characterization (laboratory parameters and oral glucose tolerance test), an ACTH assay and determination of cortisol excretion. In addition, Ga-68-NODAGA-exendin-4 PET/CT imaging will be performed in 10 patients with treatment response (decrease in HbA1c or weight loss) and 10 patients without response after GLP-1RA therapy. In 5 patients with high radiotracer uptake, an additional brain MRI scan will be performed for improved anatomical referencing.

Inclusion Criteria: Patients with treatment response: Age ≥18 years Subject is diagnosed with type 2 diabetes Subject showed response to GLP-1RA treatment Ability to sign informed consent Patients without treatment response: Age ≥18 years Subject is diagnosed with type 2 diabetes Subject showed no response to GLP-1RA treatment Ability to sign informed consent Exclusion Criteria: Liver disease Renal disease Pregnancy or the wish to become pregnant within 6 months after the study Breastfeeding Age <18 years Pituitary disorder Inability to sign informed consent Exclusion criteria for MR: Fragments, clips or devices in brain, eyes, spinal canal Implantable defibrillator or pacemaker (wires) Mandibular magnetic implants Neurostimulator, bladder stimulator, non-removable insulin pump Metal tissue-expander in chest Cochlear implant Ossicular replacement prosthesis