The effect of elexacaftor/tezacaftor/ivacaftor (ETI) on glycemia in adults with cystic fibrosis

Abstract

Background: Cystic fibrosis related diabetes (CFRD) is associated with pulmonary decline and compromised nutritional status. Emerging data suggest that CFTR dysfunction may play a direct role in the pathogenesis of CFRD; however, studies investigating the effect of CFTR modulators on glycemic outcomes in patients with cystic fibrosis (CF) have shown mixed results. The impact of elexacaftor-tezacaftor-ivacaftor (ETI) on glycemic control is currently unknown. Our objective was to investigate the effect of ETI initiation on glycemia in adults with CF using continuous glucose monitoring (CGM).

Methods: In this prospective observational study, 34 adults with CF and at least one F508del CFTR mutation wore CGM sensors for 14 days prior to starting ETI and again 3-12 months after ETI initiation. Hypoglycemia symptoms were queried at each visit, and most recent anthropometric measures and spirometry data were obtained by chart review.

Results: Twenty-three participants completed the study. Compared to baseline, average glucose (AG), standard deviation (SD), % time >200 mg/dL, and peak sensor glucose decreased with ETI treatment, and % time in target range 70-180 mg/dL increased. Improvements in glycemic parameters were most notable in individuals with CFRD. There was no significant change in CGM-measured or self-reported hypoglycemia before and after ETI initiation.

Conclusion: Initiation of ETI in adults with CF was associated with improvement CGM-derived measures of hyperglycemia and glycemic variability with no effect on hypoglycemia. Further studies are needed to investigate underlying etiology of these changes and the long-term impact of ETI on glycemic control in patients with CF.

Keywords: CFTR modulator; Continuous glucose monitoring; Cystic fibrosis related diabetes; Elexacaftor-tezacaftor-ivacaftor.

Conflict of interest statement

Declaration of Competing Interest Dr. Putman reports grants from Vertex Pharmaceuticals and the Cystic Fibrosis Foundation, outside the submitted work. Dr. Sawicki reports personal fees from Vertex Pharmaceuticals, outside the submitted work. Dr. Uluer reports grants from the Cystic Fibrosis Foundation and serves an advisory board for Vertex Pharmaceuticals and as an unpaid board member for the Cystic Fibrosis Research Institute. Dr. Kennedy reports grants from the Cystic Fibrosis Foundation. The other authors have nothing to disclose.

Copyright © 2021. Published by Elsevier B.V.

Figures

Figure 1.. Changes in CGM Measures Before and After ETI Initiation

Changes in CGM measures before and after ETI-initiation are displated for a.) AG, SD, and peak glucose reported in mg/dL, and b) CV and time spent in glycemic ranges reported in percentages. Data are displayed as mean ± SEM. * p value