Endocrine Abstracts

CFTR modulators are drugs that enhance/restore the expression, function, or stabilize the defective CFTR protein in patients with cystic fibrosis (CF). These modulators have shown marked improvements in lung function and quality of life for people with CF but their role in glucose tolerance is still unclear¹. At Nottingham Children’s Hospital, children with CF are eligible for kaftrio treatment (Elexacaftor/tezacaftor/ivacaftor CFTR modulator) from 10 years of age. We investigated if glucose tolerance improved after starting kaftrio.

Methods: The fasting glucose levels and 2hr OGTT levels 12 months prior to starting kaftrio, just before starting, and 12 months post treatment from 21 children and adolescents with CF (12 males) were compared. We also categorized the glucose response as normal, impaired, or meeting the criteria for CF-related diabetes to determine if categorical changes occurred with kaftrio treatment.

Results: Paired t-tests showed no overall significant difference between immediately pre-kaftrio fasting glucose and 12 months post kaftrio fasting glucose levels, t(20)=1.4, P=0.166. Likewise, there was no significant difference between the initial 2hr OGTT results and those 12 months after starting kaftrio t(20)=0.4, P=0.663. Comparing fasting glucose and OGTT levels from 12 months prior to starting to 12 months post-kaftrio treatment also showed no significant differences (t(20)=1.8, P=0.089 and t(20)=0.5, P=0.595, respectively). 15 patients remained with normal glucose tolerance after kaftrio treatment and one with impaired glucose tolerance (IGT). One patient went from IGT to normal glucose tolerance. In contrast, 4 patients moved to the CF-related diabetes category after kaftrio treatment.

Conclusion: This study showed no clear relationship between kaftrio treatment and glucose regulation in children. The majority of children in this study had normal glucose tolerance 12 months after starting CFTR modulator therapy. Longer term follow-up is needed to see if kaftrio delays the onset of impaired glucose tolerance known to occur with CF, in line with its protective function for pancreatic beta cells due to better activity of the CFTR protein.

¹Merjaneh L. The role of modulators in cystic fibrosis related diabetes. Journal of clinical & translational endocrinology,2022,1;27:100286