Lumacaftor/ivacaftor in cystic fibrosis: effects on glucose metabolism and insulin secretion

C. Colombo, A. Foppiani, A. Bisogno, S. Gambazza, V. Daccò, E. Nazzari, A. Leone, A. Giana, A. Mari, A. Battezzati

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The question whether the new cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs aimed at restoring CFTR protein function might improve glucose metabolism is gaining attention, but data on the effect of lumacaftor/ivacaftor treatment (LUMA/IVA) on glucose tolerance are limited. We evaluated the variation in glucose metabolism and insulin secretion in CF patients homozygous for Phe508del CFTR mutation after one-year treatment with LUMA/IVA in comparison to patients with the same genotype who did not receive such treatment. Methods: We performed a retrospective case–control study on 13 patients with a confirmed diagnosis of CF, homozygous for the Phe508del CFTR mutation, who received LUMA/IVA for one year (cases) and 13 patients with identical genotype who did not receive this treatment (controls). At the beginning and conclusion of the follow-up, all subjects received a modified 3 h OGTT, sampling at baseline, and at 30 min intervals for plasma glucose, serum insulin, and c-peptide concentrations to evaluate glucose tolerance, and quantify by modeling beta-cell insulin secretion responsiveness to glucose, insulin clearance and insulin sensitivity. Results: LUMA/IVA did not produce differences in glucose tolerance, insulin secretory parameters, clearance and sensitivity with respect to matched controls over one-year follow-up. Conclusion: We found no evidence of improvements in glucose tolerance mechanisms in patients with CF after one-year treatment with LUMA/IVA.

Original languageEnglish
JournalJournal of Endocrinological Investigation
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Glucose tolerance
  • Lumacaftor/ivacaftor
  • OGTT
  • Phe508del

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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