Impact of Elexacaftor/Tezacaftor/Ivacaftor on Glucose Tolerance and Abnormal Glucose Metabolism: A Phase 3b, Open-Label Clinical Trial
Bibliographic record
Abstract
Abstract Rationale Abnormal glucose metabolism is a common complication in people with cystic fibrosis (CF), and those with impaired glucose tolerance (IGT) or CF-related diabetes (CFRD) have increased disease burden. Elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) is safe and effective for people with CF ≥2 years of age with ELX/TEZ/IVA-responsive CFTR (CF transmembrane conductance regulator) mutations; however, efficacy on glycemic control has not been studied. Objectives To evaluate the impact of ELX/TEZ/IVA on glucose tolerance in people with CF who have IGT or CFRD. Methods In this phase 3b, open-label study, ELX/TEZ/IVA was administered for 48 weeks to participants ≥12 years of age, heterozygous for F508del and a minimal function CFTR mutation, with either IGT or CFRD. Measurements and Main Results Sixty-nine participants received ELX/TEZ/IVA. 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; 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]). Secondary endpoints were the proportion of participants with improvement in dysglycemia categorization (CFRD, IGT, normal glucose tolerance) at Week 48 and safety. 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. Conclusions 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. Clinical trial registered with www.clinicaltrials.gov (NCT 04599465).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".