759-P: Effect of Elexacaftor/Tezacaftor/Ivacaftor on Glycemic Control in Cystic Fibrosis-Related Diabetes Mellitus: A Chart Review

Abstract

Introduction: Cystic fibrosis related diabetes mellitus (CFRD) affects up to 50% of adults with cystic fibrosis (CF), causing significant morbidity. CFRD primarily causes insulin deficiency, but exacerbations of CF may result in periods of insulin resistance. Anecdotal reports have suggested improved glycemic control and reduced insulin needs with CFTR modulators. Small pilot studies have shown improved insulin secretion and glycemic control with use of cystic fibrosis transmembrane regulator (CFTR) gene modulators, but the data are conflicting. This is a retrospective observational study investigating the effect of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), the newest CFTR modulator, on glucose metabolism in CF. Methods: We identified patients enrolled in the CF clinic at Brooke Army Medical Center who were started on ELX/TEZ/IVA in the last 12 months. Chart review was performed to identify diagnosis of CFRD, glucose and HbA1c values, and insulin dose. Glycemic control was compared for the periods 6 months prior to starting ELX/TEZ/IVA vs. 6 months afterward using paired t-tests. Results: There were 10 patients with adequate data for analysis; 6 had CFRD and 4 did not. Median duration of CFRD was 10 years. Among patients without CFRD, there was no difference in FPG (p = 0.80), HbA1c (p = 0.20), or 2-hour OGTT (p = 0.09). In patients with CFRD, an improvement was seen in FPG (p=0.006) but not HbA1c (p=0.29) or insulin dose per kilogram (p=0.51). One patient did have a 55% reduction in insulin dose. Conclusion: ELX/TEZ/IVA may improve FPG in patients with CFRD but does not have a significant effect on glucose metabolism in patients without CFRD. Further research is needed to elucidate metabolic effects of CFTR modulators and patient characteristics associated with improved glycemic control. Disclosure M. Kravchenko: None. W. Warren: None.