Effect of GLP-1 Agonist Therapy on Insulin Secretion in Adults With Pancreatic Insufficient Cystic Fibrosis and Abnormal Glucose Tolerance: a Randomized, Open-label, Cross-over Trial
Diabetes is a major co-morbidity in pancreatic insufficient cystic fibrosis (PI-CF) and associated with worse outcomes. While reduced β-cell mass contributes to the insulin secretory defects that characterizes cystic fibrosis-related diabetes (CFRD), other modifiable determinants appear operative in the emergence and progression of abnormal glucose tolerance towards diabetes. Identifying interventions to preserve β-cell function are crucial for delaying and potentially preventing CFRD development. In this study, we hypothesize that weekly administration of the long-acting glucagon-like peptide-1 (GLP-1) agonist dulaglutide will improve defective early-phase insulin secretion and improve glucose tolerance during a mixed-meal tolerance test.
• 1\. Male or female, aged ≥18 years on date of consent
• 2\. Confirmed diagnosis of CF, defined by positive sweat test or Cystic Fibrosis transmembrane conductance regulator (CFTR) mutation analysis according to Cystic Fibrosis Foundation (CFF) diagnostic criteria.
• 3\. Pancreatic insufficiency defined by clinical requirement for pancreatic enzyme replacement.
• 4\. Abnormal glucose tolerance defined by OGTT criteria for EGI, IGT, or CFRD, or diagnosed CFRD.
‣ There will be no restriction on enrollment of individuals with CFRD but without fasting hyperglycemia (fasting hyperglycemia is defined as fasting glucose ≥126 mg/dL)
⁃ Individuals with CFRD and fasting hyperglycemia (defined as above or by the use of basal insulin therapy) must also have a HbA1c ≤8% and a random (non-fasting) C-peptide ≥1.2 ng/mL17; enrollment of this subgroup will be limited to n =10.
• 5\. Ability to take subcutaneous medication and be willing to adhere to the weekly administration regimen and complete study specific procedures (MMTT)
• 6\. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 6 weeks after the end of dulaglutide or observation administration; oral contraceptives, intra-uterine devices, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable