Improved glucose tolerance after initiation of Elexacaftor / Tezacaftor / Ivacaftor in adults with cystic fibrosis.
CFRD
Cystic fibrosis
Cystic fibrosis related diabetes
Elexacaftor/Tezacaftor/Ivacaftor
Glucose tolerance
OGTT
Oral glucose tolerance test
Journal
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
24
09
2022
revised:
10
01
2023
accepted:
11
01
2023
medline:
11
9
2023
pubmed:
21
1
2023
entrez:
20
1
2023
Statut:
ppublish
Résumé
The novel triple CFTR modulator therapy Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) improves lung function, body mass index (BMI), sinus clearance, and quality of life in patients with cystic fibrosis. Whether treatment with ELX/TEZ/IVA is associated with improved glucose tolerance is unknown. This cohort study included adults with CF and at least one copy of F508del.. Study assessments before treatment and at least 3 months after ELX/TEZ/IVA initiation included an oral glucose tolerance test (OGTT) with glucose and insulin measurements, BMI, lung function test, and sweat chloride levels. We used an analysis of response profiles to calculate changes in outcomes. 33 patients (27.8 ± 6.3 years; 73% male; 64% F508del homozygous) were included. After a median of 184 [IQR, 107 - 278] days following treatment initiation 16 (48.5%) patients improved their glucose tolerance category, while 13 (39.4%) remained unchanged and 4 (12.1%) deteriorated. Overall, 60, 90 and 120 min OGTT glycemia decreased significantly from 11.9 ± 2.7 mmol/l to 10.6 ± 2.8 mmol/l (p = 0.012), 10.4 ± 3.0 mmol/l to 8.4 ± 3.6 mmol/l (p = 0.002) and 7.3 ± 3.1 mmol/l to 5.7 ± 3.0 mmol/l (p = 0.012). HbA In adult patients with CF and at least one copy of F508del, treatment with the triple CFTR modulator was associated with possible improvement of glucose tolerance without increases of insulin secretion. Early initiation of treatment as assessed through long-term prospective trials is mandatory to demonstrate if decreased glucose control is preventable or even reversible.
Sections du résumé
BACKGROUND
The novel triple CFTR modulator therapy Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) improves lung function, body mass index (BMI), sinus clearance, and quality of life in patients with cystic fibrosis. Whether treatment with ELX/TEZ/IVA is associated with improved glucose tolerance is unknown.
METHODS
This cohort study included adults with CF and at least one copy of F508del.. Study assessments before treatment and at least 3 months after ELX/TEZ/IVA initiation included an oral glucose tolerance test (OGTT) with glucose and insulin measurements, BMI, lung function test, and sweat chloride levels. We used an analysis of response profiles to calculate changes in outcomes.
RESULTS
33 patients (27.8 ± 6.3 years; 73% male; 64% F508del homozygous) were included. After a median of 184 [IQR, 107 - 278] days following treatment initiation 16 (48.5%) patients improved their glucose tolerance category, while 13 (39.4%) remained unchanged and 4 (12.1%) deteriorated. Overall, 60, 90 and 120 min OGTT glycemia decreased significantly from 11.9 ± 2.7 mmol/l to 10.6 ± 2.8 mmol/l (p = 0.012), 10.4 ± 3.0 mmol/l to 8.4 ± 3.6 mmol/l (p = 0.002) and 7.3 ± 3.1 mmol/l to 5.7 ± 3.0 mmol/l (p = 0.012). HbA
CONCLUSION
In adult patients with CF and at least one copy of F508del, treatment with the triple CFTR modulator was associated with possible improvement of glucose tolerance without increases of insulin secretion. Early initiation of treatment as assessed through long-term prospective trials is mandatory to demonstrate if decreased glucose control is preventable or even reversible.
Identifiants
pubmed: 36669960
pii: S1569-1993(23)00006-1
doi: 10.1016/j.jcf.2023.01.004
pii:
doi:
Substances chimiques
elexacaftor
RRN67GMB0V
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
ivacaftor
1Y740ILL1Z
tezacaftor
0
Aminophenols
0
Benzodioxoles
0
Glucose
IY9XDZ35W2
Chloride Channel Agonists
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
722-729Informations de copyright
Copyright © 2023. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest C. Steinack and M. Ernst report speaker fees from Vertex®, outside the submitted work. M. Ernst reports congress and speaker fees from Novo Nordisk Pharma AG and Eli Lilly outside the submitted work. T. Gaisl reports consulting fees from Bayer AG, outside the submitted work. All other authors report no conflicts of interest.