SYSTEMATIC REVIEW article
Front. Endocrinol.
Sec. Pediatric Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1623654
Impact of CFTR modulators on glucose homeostasis in children and young adults with CFRD: a systematic review
Provisionally accepted
Paola Giordano1
Giuseppina Leonetti1Vanja Granberg1Rosa Maria Pia Casolino1
Giuseppe Lassandro1Maurizio Delvecchio2*
Giovanna Linguiti1,3- 1Department of Interdisciplinary Medicine, Pediatric Unit “B. Trambusti”, Cystic Fibrosis Regional Reference Center, University of Bari “Aldo Moro”, Bari, Italy
- 2Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
- 3University of Bari Aldo Moro, Bari, Italy
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Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene, leading to impaired chloride transport, thickened mucus, and multi-organ dysfunction. Among its complications, cystic fibrosis-related diabetes (CFRD) is a major concern, characterized by progressive β-cell dysfunction and insulin deficiency. The advent of CFTR modulators, including ivacaftor, lumacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor (ETI), has revolutionized CF management by improving pulmonary function, nutritional status, and overall survival. However, their effects on glucose metabolism remain under investigation. This systematic review (systematic review registration: PROSPERO 2025 CRD420251021499) analyzes recent evidence on the impact of CFTR modulators on CFRD in children and young adults. Ivacaftor demonstrates potential benefits in glucose regulation, enhancing insulin secretion and glucagon control, particularly in patients with gating mutations. Conversely, lumacaftor/ivacaftor exhibits inconsistent effects, with some studies indicating glucose tolerance improvements while others report insulin sensitivity decline. ETI therapy shows modest but generally positive effects on glycemic control, with reductions in HbA1c and fasting glucose, though without significant changes in insulin secretion. While CFTR modulators improve systemic health, their role in directly preventing or reversing CFRD remains unclear. Further longitudinal studies are needed to optimize therapeutic strategies and elucidate the long-term metabolic effects of CFTR modulation in CF patients.
Keywords: Cystic Fibrosis, CFTR modulators, CFRD, glucose metabolism, Lumacaftor/ivacaftor, elexacaftor-ivacaftor-tezacaftor
Received: 06 May 2025; Accepted: 18 Jul 2025.
Copyright: © 2025 Giordano, Leonetti, Granberg, Casolino, Lassandro, Delvecchio and Linguiti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Maurizio Delvecchio, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
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