O-18: Assessment of the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in cystic fibrosis patients
T Boueri Ramos, A Batista Coelho, F Giuzio Vignati, T Laks, N Damaceno, L de Freitas Pires Cudízio, L E Procopio CalliariAbstract
Introduction
Cystic Fibrosis-Related Diabetes (CFRD) affects approximately 20–50% of individuals with cystic fibrosis (CF), and is associated with more frequent pulmonary exacerbations, reduced lung function, lower weight, and early mortality. ETI, the most recent CFTR modulator approved by the FDA, has proven highly effective in reducing pulmonary exacerbations and improving lung function, but its impact on glucose metabolism remains unclear.
Objectives
To evaluate the impact of ETI on glucose metabolism in patients with CFRD, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT).
Methods
A prospective observational study with 88 CF patients (age 6–41), 54.54% females, from Santa Casa de São Paulo. Patients were divided into three groups: CFRD (n=15), IGT (n=11) and NGT (n=62), evaluated before and 3–12 months after ETI initiation, using HbA1c, fasting glucose, BMI, FEV1, and oral glucose tolerance test (OGTT) where applicable. In patients with CFRD, the total daily insulin dose (TDD) per body weight (IU/kg/day) was calculated.
Results
Mean BMI increased significantly across all groups (p<0.05). FEV1 improved in 88.6% of patients. In the NGT group only 1.6% progressed to IGT, and 3.2% to CFRD. In the IGT group, over half (54.5%) normalized their OGTT, showing a relevant improvement in the 120-minute OGTT value (p=0.008), and none developed CFRD. In the CFRD group, despite the increase in BMI, TDD decreased significantly (p=0.02), and insulin was discontinued in 26,6% of patients. HbA1c showed a non-significant declining trend across all groups.
Conclusions
ETI appears to have a positive, though modest, impact on glucose metabolism in CF patients, reducing insulin requirements in CFRD and normalizing glucose tolerance in IGT patients. Weight gain observed may modify insulin resistance, suggesting an even more expressive impact of ETI on pancreatic function. Larger multicenter studies are needed to confirm these findings.