Long-term therapy with CFTR modulators consistently improves glucose metabolism in adolescents and adults with cystic fibrosis

Amitay Cohen; Alon Mass; Joel Reiter; David Haim Zangen; Malena Cohen-Cymberknoh

doi:10.1016/j.rmed.2024.107664

Long-term therapy with CFTR modulators consistently improves glucose metabolism in adolescents and adults with cystic fibrosis

Respir Med. 2024 May 16:228:107664. doi: 10.1016/j.rmed.2024.107664. Online ahead of print.

Authors

Amitay Cohen¹, Alon Mass², Joel Reiter³, David Haim Zangen¹, Malena Cohen-Cymberknoh⁴

Affiliations

¹ Division of Pediatric Endocrinology, Hadassah Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Israel.
² Faculty of Medicine, Hebrew University of Jerusalem, Israel.
³ Faculty of Medicine, Hebrew University of Jerusalem, Israel; Pediatric Pulmonary Unit and Cystic fibrosis Center, Hadassah Medical Center, Jerusalem, Israel.
⁴ Faculty of Medicine, Hebrew University of Jerusalem, Israel; Pediatric Pulmonary Unit and Cystic fibrosis Center, Hadassah Medical Center, Jerusalem, Israel. Electronic address: malena@hadassah.org.il.

PMID: 38759874
DOI: 10.1016/j.rmed.2024.107664

Abstract

Background: Impaired glycemic control and the subsequent development of Cystic fibrosis Related Diabetes (CFRD) are prevalent complications, affecting up to 50 % of adults with cystic fibrosis (CF). CFTR modulator (CFTRm) therapies improve pulmonary functions, reduce exacerbation rates, increase survival in people with CF (pwCF) and appear to have a positive effect on extrapulmonary manifestations, such as nutritional state, improvements in upper respiratory symptoms, and quality of life. Initial findings indicate that CFTRm may have a positive impact on short-term glycemic control; however, long-term effects remain uncertain at present.

Methods: In this retrospective study, data were collected and analyzed on 15 pwCF, ages 13-37 years, started on CFTRm therapy. Oral Glucose Tolerance Test (OGTT) results were compared pre- and post-CFTRm therapy.

Results: The 120-min OGTT value decreased from 159.7 mg/dL to 130.4 mg/dL post-CFTRm (p = 0.047). The average time elapsed between the two OGTTs was 49.87 months (ranging 9-157 months, median 38 months). Glycemic status improved in six pwCF (two CFRD to normal (NGT)/indeterminate (INDET) glucose tolerance; two impaired glucose tolerance (IGT) to INDET; two INDET to NGT) and worsened in one (IGT to CFRD). Six pwCF and NGT remained stable with no changes in glycemic status throughout the follow-up period.

Conclusions: CFTRm therapy may decelerate the glycemic control deterioration in pwCF over an extended period. These findings indicate the need for periodic OGTTs following the initiation of CFTRm therapy to appropriately adjust insulin requirements and prevent hypoglycemia. Further larger cohorts are required to authenticate and substantiate these findings.

Keywords: CFRD; CFTR modulators; INDET; Impaired OGTT; NGT.