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Lumacaftor/ivacaftor therapy fails to increase insulin secretion in F508del/F508del CF patients. J Cyst Fibros 2021 Mar;20(2):333-338

Date

09/13/2020

Pubmed ID

32917547

Pubmed Central ID

PMC7937760

DOI

10.1016/j.jcf.2020.09.001

Scopus ID

2-s2.0-85090490297   18 Citations

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.

Author List

Moheet A, Beisang D, Zhang L, Sagel SD, VanDalfsen JM, Heltshe SL, Frederick C, Mann M, Antos N, Billings J, Rowe SM, Moran A, PROSPECT Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network

Author

Nicholas Antos MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aminophenols
Aminopyridines
Benzodioxoles
Child
Chloride Channel Agonists
Cystic Fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator
Drug Combinations
Female
Glucose Tolerance Test
Homozygote
Humans
Longitudinal Studies
Male
Middle Aged
Mutation
Quinolones