Effect of one-year lumacaftor–ivacaftor treatment on glucose tolerance abnormalities in cystic fibrosis patients

Cystic fibrosis-related diabetes and lung disease: an update

“…Looking to the future, perhaps specific treatment for CFRD may not be needed if CFTR modifiers are initiated early and protect the endocrine and exocrine pancreas from inflammation and resultant destruction. Even though more recent evidence suggests that CFTR may not be present in the beta cells of the pancreas and that dysglycaemia may occur secondary to changes in the inflammatory milieu of the pancreas [22], there does appear to be some modest evidence that modifiers improve glucose abnormalities [130][131][132][133]. However, longitudinal CFTR modifier studies need to be undertaken with glucose abnormalities as the primary outcome to determine if new modifiers treat, slow the onset or even prevent CFRD.…”

In Silico Molecular Dynamics Docking of Drugs to the Inhibitory Active Site of SARS-CoV-2 Protease and Their Predicted Toxicology and ADME

“…Trametinib (Rank 108, BE=-8.4, B08911) is indicated for the treatment of unresectable or metastatic melanoma [107] , advanced rectal [111] , breast [112] , biliary [113] , colorectal, non-small cell lung, and pancreatic cancer [114] . Lumacaftor (Rank 117, BE=-8.4, B09280) is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who are homozygous for the F508del mutation in the CFTR gene [115][116][117] . Ergotamine (Rank 154, BE=-8.3, B00696) is for use as therapy to abort or prevent vascular headache, e.g., migraine, migraine variants, or so called "histaminic cephalalgia" [118][119][120] .…”

Review of CFTR Modulators 2020

“…Many pwCF who do not yet have CFRD have impaired glucose tolerance (IGT). Part of the pathophysiology of IGT and CFRD involves decreased insulin secretion, insulin resistance and hepatic glucose control abnormalities, along with other mechanisms of insulin insufficiency such as destruction of the pancreas, islet cell inflammation, and oxidative stress 39 . In past studies of those with the G551D mutation, iva improved insulin secretion 38 .…”

“…A prospective, observational study in France, examined the effect of lum/iva on glucose tolerance abnormalities in pwCF between ages 12-61 years (average 24 years). At baseline, 78% of 40 patients had IGT, and 22% had newly diagnosed CFRD, while patients with fasting hyperglycemia, requiring insulin therapy or, with normal glucose tolerance (NGT) were excluded 39 . After 1 year of lum/iva treatment, based on 2-hour glucose levels in the oral glucose tolerance test (OGTT), 57.5% improved their glucose tolerance, and 42.5% had no change (p<0.001).…”