Changes in glucose metabolism and metabolic outcomes following ETI initiation in patients with cystic fibrosis

BACKGROUND: Cystic fibrosis-related diabetes (CFRD) is a frequent complication in people with cystic fibrosis (pwCF). CFTR modulators such as Elexacaftor/Tezacaftor/Ivacaftor improve pulmonary outcomes, but their effect on glucose metabolism remains uncertain. This study evaluated changes in oral glucose tolerance after initiation of ETI. METHODS: In this uncontrolled retrospective single-center study, pwCF aged ≥10 years receiving ETI underwent a 2-hour oral glucose tolerance test before treatment, at 12 and 24 months. Participants were classified by baseline glucose tolerance: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or CFRD. Secondary outcomes included changes in body weight, FEV1, lipids, and HbA1c. RESULTS: Of 68 pwCF (median age 23 years), 56% had NGT, 25% IGT, and 19% CFRD at baseline. Among 62 participants with OGTT data at baseline and 24 months, glucose tolerance remained stable in 48 (77%), improved in 10 (16%), and worsened in 4 (6%). Median HbA1c decreased from 5.5% to 5.3% (P<0.001). In 52 adults, median body weight increased by +7.3 kg (P<0.001). At year 1, pwCF with deteriorated OGTT showed a greater increase in total cholesterol compared with those with stable or improved OGTT (+26 vs. +5 mg/dL, P=0.008). CONCLUSIONS: Glucose tolerance improved in some pwCF after ETI initiation, but responses were heterogeneous and improvements were not consistently sustained. A greater cholesterol increase in a small exploratory subgroup with worsening glucose tolerance requires confirmation.