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The following is a summary of “Preservation of β-cell Function in Pancreatic Insufficient Cystic Fibrosis With Highly Effective CFTR Modulator Therapy,” published in the January 2024 issue of Endocrinology by Flatt, et al.

Elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta) has shown promise in improving cystic fibrosis transmembrane conductance regulator (CFTR) function and addressing the associated insulin secretory defects in pancreatic insufficient cystic fibrosis (PI-CF), potentially impacting clinical outcomes. For a longitudinal case-control study, researchers sought to evaluate changes in β-cell function and secretory capacity measures over two visits in individuals with PI-CF following initiation of ETI, compared to matched controls not yet treated with CFTR modulator therapy.

Nine ETI participants (mean age 25 ± 5 years) and 8 matched controls were followed up after a median of 5 (interquartile range: 4-7) years and 3 (interquartile range: 2-3) years, respectively (P < .01). ETI initiation occurred approximately 1 year before follow-up. Clinical outcomes, glucose-potentiated arginine, and mixed-meal tolerance test measures were assessed using nonparametric testing comparisons of within- and between-group changes.

In controls, glucose-potentiated insulin and C-peptide responses to glucose-potentiated arginine deteriorated, while no significant changes were observed in the ETI group, with significant differences in C-peptide changes between groups (P < .05). Controls exhibited deterioration in basal proinsulin secretory ratio, whereas the ETI group showed improvement, along with enhanced maximal arginine-induced proinsulin secretory ratio (P < .05 for all comparisons). During mixed-meal tolerance testing, early insulin secretion improved in the ETI group, indicated by faster insulin secretory rate kinetics.

ETI appeared to preserve β-cell function in PI-CF by enhancing glucose-dependent insulin secretion, improving proinsulin processing, and enhancing meal-related insulin secretion. Future research should investigate whether early intervention with ETI can prevent glucose tolerance deterioration in PI-CF.

Reference: academic.oup.com/jcem/article-abstract/109/1/151/7232815