Am J Respir Crit Care Med. 2025 Oct;211(10):1926-1934. doi: 10.1164/rccm.202411-2312OC.

Phase 3b, open-label study

≥12 years of age, heterozygous for F508del and a minimal function CFTR mutation, with either IGT or CFRD

Elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) 48 weeks

The primary endpoint was change in blood glucose concentration after a 2-hour oral glucose tolerance test from baseline to the average of Week 36 and Week 48. Secondary endpoints were the proportion of participants with improvement in dysglycemia categorization (CFRD, IGT, normal glucose tolerance) at Week 48 and safety.

Participants had a mean change of -35.0 mg/dl (95% confidence interval [CI], -49.2 to -20.7 mg/dl; P < 0.0001) (-1.9 mmol/L [95% CI, -2.7 to -1.2 mmol/L]). Among participants with abnormal glucose tolerance at baseline, 37.7% (95% CI, 24.8 to 52.1) had improvements in dysglycemia categorization at Week 48. Overall, 35.5% of participants had normal glucose tolerance at Week 48 compared with 13.0% at baseline. Safety was consistent with the established safety profile of ELX/TEZ/IVA.

ELX/TEZ/IVA treatment led to clinically meaningful improvements in blood glucose regulation, with significant within-group decreases in blood glucose concentrations after oral glucose tolerance testing and improved dysglycemia categorization in people with CF with early IGT or CFRD.