Effect of Elexacaftor/Tezacaftor/Ivacaftor on Glucose Tolerance in Adolescents With Cystic Fibrosis

Abstract

Context: Highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators, such as elexacaftor/tezacaftor/ivacaftor (ETI), herald a new era in therapeutic strategy of cystic fibrosis (CF). ETI’s effect on glucose tolerance remains controversial. Objective: The study was undertaken to evaluate the effect of ETI treatment on glucose tolerance in youths with CF. Methods: All the participants underwent a baseline oral glucose tolerance test (OGTT) before ETI initiation (M0) and 12 months (M12), and at 24 months if possible. The cohort was stratified in two subgroups based on the baseline OGTT: normal glucose tolerance (NGT) and abnormal glucose tolerance (AGT) defined by impaired fasting glucose or impaired glucose tolerance or diabetes not requiring insulin treatment. Results: We included 106 adolescents with CF (age 14.1 ± 1.5 years), 75 with NGT, and 31 with AGT. The baseline characteristics of the two groups were similar except for a higher glucose level at 1- and 2-hour OGTT in the AGT group. ETI induced an increase in body mass index z score and in forced expiratory volume in 1 second (FEV1) (P