Lumacaftor/ivacaftor therapy fails to increase insulin secretion in F508del/F508del CF patients

PROSPECT Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Glucose tolerance abnormalities including cystic fibrosis related diabetes (CFRD) are common in patients with cystic fibrosis (CF). The underlying pathophysiology is not fully understood. Emerging evidence suggests that CFTR dysfunction may directly or indirectly impact β-cell function, offering the potential for improvement with CFTR modulator therapy. In small pilot studies, treatment with ivacaftor improved insulin secretion in patients with the G551D CFTR mutation. In the current study, we examined the impact of lumacaftor/ivacaftor therapy on glucose tolerance and insulin secretion in patients with CF who were homozygous for the F508del mutation. Methods: 39 subjects from the PROSPECT Part B study who had been prescribed lumacaftor/ivacaftor by their CF care team at a CF Foundation's Therapeutic Development Network center were recruited. Subjects underwent 2-hour oral glucose tolerance tests (OGTTs) at baseline prior to first dose of lumacaftor/ivacaftor, and at 3, 6 and 12 months on therapy. OGTT glucose, insulin and c-peptide parameters were compared. Results: Compared to baseline, OGTT fasting and 2 hour glucose levels, glucose area under the curve, insulin area under the curve and time to peak insulin level were not significantly different at 3, 6 and 12 months on lumacaftor/ivacaftor therapy. Similarly, C-peptide levels were no different. Conclusions: Lumacaftor/ivacaftor therapy did not improve insulin secretion or glucose tolerance in patients with CF who were homozygous for the F508del mutation.

Original languageEnglish (US)
Pages (from-to)333-338
Number of pages6
JournalJournal of Cystic Fibrosis
Volume20
Issue number2
DOIs
StatePublished - Mar 2021

Bibliographical note

Funding Information:
Amir Moheet has no declarations of interest. Daniel Beisang has no declarations of interest. Lin Zhang has no declarations of interest. Scott D. Sagel received grant funding from the CFF to conduct this study. Jill M. VanDalfsen has no declarations of interest. Sonya L. Heltshe has no declarations of interest. Carla Frederick has no declarations of interest. Michelle Mann has no declarations of interest. Nicholas Antos has no declarations of interest. Joanne Billings has no declarations of interest. Steven M. Rowe provided consulting services for Vertex Pharmaceuticals, and received research product for investigator initiated research and trial support from that company. Antoinette Moran served on a medical advisory board for Vertex Pharmaceuticals. She received grant funding from the CFF to conduct this study.

Funding Information:
This work was funded by the Cystic Fibrosis Foundation (SAGEL14K1). The Cystic Fibrosis Foundation had no role in the study design, data analysis, or manuscript writing.

Publisher Copyright:
© 2020

Keywords

  • CFRD
  • Cystic fibrosis
  • Insulin secretion
  • Orkambi

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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