SUN-567 - Highly Effective CFTR Modulators (HEMT) Are Associated with Lower Prevalence of Cystic Fibrosis–Related Diabetes: A Real-World Cohort Study

Background:
While the lifespan of people with cystic fibrosis (PwCF) has increased substantially, up to 50% will develop CF-related diabetes (CFRD) which drives morbidity and mortality. Highly effective cystic fibrosis transmembrane conductance regulator therapies (HEMT) are now the mainstay of CF treatment but their impact on risk of CFRD remains uncertain.

Methods:
We conducted a retrospective analysis of 2015-2024 electronic health record data from a large regional health system. We included adult patients (age>18years) with CF (baseline was the time of CF diagnosis). We excluded patients with steroid-associated hyperglycemia, post-transplant diabetes, or type 1 or type 2 diabetes prior to the baseline visit. Our primary outcome of CFRD was defined by OGTT ≥200 mg/dL, HbA1c ≥6.5%, use of antihyperglycemic therapy, or diabetes-related diagnostic codes. HEMT exposure was defined as having one or more HEMT prescription order. We compared rates of CFRD among CF patients who were and were not exposed to HEMT. Summary statistics and bivariate tests for differences (t-tests; chi-square) between HEMT users were conducted.

Results:
Our analytic sample included 127 adults with CF (N=92 with and N=35 without HEMT exposure). Among HEMT users, 98% received elexacaftor/tezacaftor/ivacaftor; 17% ivacaftor and 9% tezacaftor/ivacaftor. Patients were, on average, 31 years old at time of CF diagnosis, predominantly female (57%), and non-Hispanic (73%). Baseline demographics and clinic characteristics were similar between groups expect, including with no reliable differences in pancreatitis or pancreatic insufficiency or inpatient utilization in the 12 months prior to baseline. BMI was higher among those exposed to HEMT (23.0 vs. 20.8 kg/m², p=0.003). In our adjusted model, CFRD prevalence was significantly lower among HEMT users (8% vs 49%, p< 0.001).

Conclusions:
HEMT use was associated with a marked reduction in CFRD prevalence. These findings provide supportive evidence for further investigation in larger, adequately powered prospective studies as well as time-to-CFRD analyses.

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