CFTR Modulator Therapy and Glycemic Control: A Meta-Analysis

CONTEXT: Cystic fibrosis-related diabetes significantly impacts health outcomes of people with cystic fibrosis (CF). Understanding the effects of CF transmembrane conductance regulator modulator (CFTRm) therapy on glycemic control is crucial for improving overall health in CF. OBJECTIVE: To evaluate the impact of CFTRm therapy on glycemic control in people with CF. DATA SOURCES: A comprehensive literature search was conducted from January 1, 2011, to September 19, 2024, in PubMed, Embase, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: Eligible studies included interventional trials comparing CFTRm therapy to no treatment or placebo and observational studies reporting glycemic outcomes-assessed by oral glucose tolerance test or continuous glucose monitoring-pretherapy and on therapy or between treated individuals and controls. DATA EXTRACTION: Two authors independently extracted data with full adherence to the Cochrane Handbook. RESULTS: Elexacaftor/tezacaftor/ivacaftor therapy (ETI) significantly improved 120-minute glucose levels (mean difference, -24.30 mg/dL; 95% CI, -44.82 to -3.96) and lowered hemoglobin A1c (HbA1c) levels (mean difference, -0.44%; 95% CI, -0.75 to -0.13). Regression analyses showed that earlier ETI therapy initiation was associated with lower HbA1c values (P = .03). In contrast, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and ivacaftor monotherapy were not associated with significant changes in any assessed outcomes. LIMITATIONS: Our analyses may underestimate the endocrine effects of CFTRm therapies, as most included papers assessed pre- and on-therapy outcomes in the same patients, potentially overlooking the gradual deterioration of glycemic control. CONCLUSIONS: ETI therapy significantly improves glycemic control in CF, particularly when initiated at a young age. Further research is needed to confirm and detail these findings.