Improved glucose tolerance after initiation of Elexacaftor / Tezacaftor / Ivacaftor in adults with cystic fibrosis

Steinack, Carolin; Ernst, Matthias; Beuschlein, Felix; Hage, René; Roeder, Maurice; Schuurmans, Macé M.; Schmid, Christoph; Gaisl, Thomas

doi:10.1016/j.jcf.2023.01.004

Cited by 20 publications

(16 citation statements)

References 30 publications

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“…Two studies by Steinack et al and Korten et al support this notion, as they reported improvements in glucose tolerance using OGTTs after initiation of IVA/TEZ/ELX, without changes in insulin secretion. Both speculate that triple modulator therapy may have an indirect effect on glucose tolerance through an improved insulin sensitivity or overall reduction in inflammation 34,35 . In contrast to these studies, Chan et al showed an increase in both insulin secretion and insulin resistance 11 months after initiation of IVA/TEZ/ELX 36 .…”

Section: Discussionmentioning

confidence: 99%

Changes in glucose tolerance in people with cystic fibrosis after initiation of first‐generation CFTR modulator treatment

Ekblond,

Nielsen,

Højte

et al. 2023

Pediatric Pulmonology

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BackgroundCystic fibrosis transmembrane conductance regulator (CFTR) modulators have been shown to have a beneficial effect on pulmonary function and nutritional status in patients with cystic fibrosis (CF), but the extent to which they affect glucose tolerance is not fully understood. In the current study, we evaluated the change in glucose tolerance and insulin secretion after first‐generation CFTR modulator treatment in adults with CF.MethodsWe performed a longitudinal observational study with an oral glucose tolerance test performed at baseline and after three and a half years of follow‐up. The test comprised glucose, C‐peptide and insulin measured at fasting, 1 h, and 2 h, and HbA1c at fasting. We compared changes in parameters of glucose tolerance and insulin secretion from baseline to follow‐up.ResultsAmong 55 participants, 37 (67%) were treated with a first‐generation CFTR modulator for a median of 21 months. Glucose levels were unchanged in both the treated and untreated group. In the treated group, C‐peptide levels declined, yet no significant differences in glucose, insulin, and C‐peptide levels were observed between the groups. HbA1c increased in both groups, while no significant change in the insulin sensitivity indices was detected in either group. However, homeostatic model assessment for insulin resistance tended to decline in the treated group, whilst tending towards an increase in the untreated group. The difference between the groups reached statistical significance (p = 0.040).ConclusionTreatment with first‐generation CFTR modulators, mainly tezacaftor/ivacaftor, did not seem to be associated with glucose tolerance nor insulin secretion in adults with CF. However, CFTR modulators may still have a beneficial effect on insulin sensitivity.

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Section: Discussionmentioning

confidence: 99%

Changes in glucose tolerance in people with cystic fibrosis after initiation of first‐generation CFTR modulator treatment

Ekblond,

Nielsen,

Højte

et al. 2023

Pediatric Pulmonology

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“…Continuous glucose monitoring (CGM) and oral glucose tolerance tests (OGTT) did not detect any difference in glucose patterns after several months of ELX/TEZ/IVA therapy in three studies (Chan et al, 2022;Crow et al, 2022;Piona et al, 2022). In contrast, glucose patterns again assessed by CGM or OGTT improved in three other studies (Korten et al, 2022;Scully et al, 2022;Steinack et al, 2023). Thus, we still do not know whether or not ELX/TEZ/IVA ameliorate glucose homeostasis and/or any of its direct determinants.…”

Section: Cftr Genotypementioning

confidence: 97%

Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor

Tümmler

2023

Front. Pharmacol.

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Triple combination therapy with the CFTR modulators elexacaftor (ELX), tezacaftor (TEZ) and ivacaftor (IVA) has been qualified as a game changer in cystic fibrosis (CF). We provide an overview of the body of literature on ELX/TEZ/IVA published between November 2019 and February 2023 after approval by the regulators. Recombinant ELX/TEZ/IVA-bound Phe508del CFTR exhibits a wild type conformation in vitro, but in patient’s tissue a CFTR glyoisoform is synthesized that is distinct from the wild type and Phe508del isoforms. ELX/TEZ/IVA therapy improved the quality of life of people with CF in the real-life setting irrespective of their anthropometry and lung function at baseline. ELX/TEZ/IVA improved sinonasal and abdominal disease, lung function and morphology, airway microbiology and the basic defect of impaired epithelial chloride and bicarbonate transport. Pregnancy rates were increasing in women with CF. Side effects of mental status changes deserve particular attention in the future.

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“…These findings are also in line with those reported by Korten and collaborators, which verified similar results of ETI therapy in 16 adolescents with CF in an observational pilot study [ 102 ]. Steinack and collaborators also reported changes in oral glucose tolerance tests in PwCF with pancreatic insufficiency receiving ETI therapy for at least three months [ 105 ]. During the test, glucose levels significantly reduced after 60, 90, and 120 min, indicating an improved glucose tolerance.…”

Section: Clinical Outcomes Of Eti Therapy In Case Reports Observation...mentioning

confidence: 99%

“…During the test, glucose levels significantly reduced after 60, 90, and 120 min, indicating an improved glucose tolerance. A decrease in the inflammatory status was observed with a reduction in circulating C-reactive protein, IgG, and IgE levels, which might have an indirect impact on the improved oral glucose tolerance [ 105 ]. Aiming to further investigate the effects of ETI therapy on glycemia and pancreatic function, Chan and collaborators collected data from 12 youth and adults with CF before and after at least 8 weeks of the therapy [ 103 ].…”

Section: Clinical Outcomes Of Eti Therapy In Case Reports Observation...mentioning

confidence: 99%

Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis

et al. 2023

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Cystic fibrosis (CF) is a potentially fatal monogenic disease that causes a progressive multisystemic pathology. Over the last decade, the introduction of CF transmembrane conductance regulator (CFTR) modulator drugs into clinical practice has profoundly modified the lives of many people with CF (PwCF) by targeting the fundamental cause of the disease. These drugs consist of the potentiator ivacaftor (VX-770) and the correctors lumacaftor (VX-809), tezacaftor (VX-661), and elexacaftor (VX-445). In particular, the triple combination of CFTR modulators composed of elexacaftor, tezacaftor, and ivacaftor (ETI) represents a life-changing therapy for the majority of PwCF worldwide. A growing number of clinical studies have demonstrated the safety and efficacy of ETI therapy in both short- and long-term (up to two years of follow-up to date) and its ability to significantly reduce pulmonary and gastrointestinal manifestations, sweat chloride concentration, exocrine pancreatic dysfunction, and infertility/subfertility, among other disease signs and symptoms. Nevertheless, ETI therapy-related adverse effects have also been reported, and close monitoring by a multidisciplinary healthcare team remains vital. This review aims to address and discuss the major therapeutic benefits and adverse effects reported by the clinical use of ETI therapy for PwCF.

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Improved glucose tolerance after initiation of Elexacaftor / Tezacaftor / Ivacaftor in adults with cystic fibrosis

Cited by 20 publications

References 30 publications

Changes in glucose tolerance in people with cystic fibrosis after initiation of first‐generation CFTR modulator treatment

Changes in glucose tolerance in people with cystic fibrosis after initiation of first‐generation CFTR modulator treatment

Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor

Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis

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