Hemoglobin A1c in youth and adults with cystic fibrosis related diabetes decreases after elexacaftor-tezacaftor-ivacaftor

Abstract

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has been highly effective for improving pulmonary disease and nutritional outcomes. However, the effect of this therapy on glycemic control in people with cystic fibrosis related diabetes (CFRD) is unclear. This study aimed to examine real-world effects of ETI on glycemia as captured by hemoglobin A1c (HbA1c) in people with pre-existing CFRD.

Methods: Retrospective chart review was performed at 4 US CF centers. Individuals with CFRD included in the study started ETI before December 2020, and had an HbA1c within 1 year before and up to 2 years after ETI initiation. A sub-analysis comparing CGM data and insulin dosing within the year before and after ETI was performed. Summary statistics were calculated and within-subject results compared.

Results: A total 175 individuals with CFRD had HbA1c data before and after ETI. Mean (±SD) age was 32.4 (±12.4) years, 49.1 % female. HbA1c were compared a median (IQR) of -40 (-93, 0) days before and 290 (107, 441) days after ETI initiation. Median (IQR) HbA1c decreased from 6.4 % (5.8, 7.2) to 6.0 % (5.5, 6.8), p<0.001. A subgroup of 13 individuals had CGM and basal insulin data for comparison. No changes were observed in CGM metrics, however, basal insulin dose in these patients decreased (p=0.03).

Conclusion: Findings suggest clinical improvements in glycemia following ETI initiation in people with CFRD. Further studies are required to better understand the mechanisms by which ETI may modulate insulin and glucose dynamics in individuals with existing CFRD.

Keywords: Continuous glucose monitoring; Cystic fibrosis related diabetes; Elexacaftor-tezacaftor-ivacaftor; Hemoglobin A1c.