CF drug improves blood sugar control, study suggests
Glucose levels improve for patients with, without CF-related diabetes
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Trikafta (elexacaftor, tezacaftor, and ivacaftor) may improve blood sugar control in people with cystic fibrosis (CF), including those with CF-related diabetes, or CFRD, a study showed.
After about one year of treatment, patients with CFRD showed clinically meaningful reductions in glycated hemoglobin (HbA1c), a measure of average blood sugar (glucose) levels over the previous two to three months. Those without diabetes processed glucose more efficiently, with many returning to normal glucose tolerance (the body’s response to sugar).
The researchers said the “findings add to growing evidence that glucose metabolism can improve with [Trikafta] in [people with CF]. Rather than assuming inevitable progression, clinicians should consider reassessing glycaemic [blood sugar] status after modulator initiation.”
The study, “Triple combination cystic fibrosis transmembrane receptor modulator effects on glycaemia and insulin kinetics in cystic fibrosis with and without diabetes,” was published in the Internal Medicine Journal.
Diabetes as common complication
CF is caused by mutations in the gene that provides instructions to make CFTR, a protein that’s crucial for regulating the production of mucus. The absence or dysfunction of CFTR results in the production of thick, sticky mucus that builds up, leading to most CF symptoms.
CFRD is a common complication of CF characterized by elevated blood glucose levels. It occurs as a result of mucus accumulation in the pancreas, which leads to insufficient production of insulin, a hormone that promotes glucose uptake by the body’s cells, and to insulin resistance, when cells don’t respond properly to insulin.
Trikafta, marketed by Vertex Pharmaceuticals, is an approved CFTR modulator, designed to boost the function of defective CFTR in CF patients with certain CFTR mutations. While most research on CFTR modulators has focused on how these treatments affect lung health, emerging evidence suggests it may also help treat CFRD.
To learn more, researchers in Australia conducted a study in a hospital in Sydney involving 61 adults — 23 with CFRD and 38 without the condition — with a mean age of about 33. All participants with known genetic profiles had F508del mutations, the most common CF-causing mutation, in at least one CFTR gene copy.
All patients with CFRD and 86.8% of those without it had pancreatic insufficiency, a common CF complication in which thick mucus blocks the release of digestive enzymes from the pancreas. Lung function was significantly worse in patients with CFRD.
Participants had received Trikafta for a little more than one year on average, and a significant proportion (34.8% of CFRD and 52.6% of non-CFRD patients) had previously been treated with other CFTR modulators.
In the CFRD group, average HbA1c levels fell by 0.5%, from 6.6% to 6.1%. While the change was not statistically significant, the team noted that it is considered clinically relevant. Patients also received a lower insulin dose, although this difference was also nonsignificant.
In participants without CFRD, Trikafta significantly reduced blood sugar levels at one hour and two hours on an oral glucose tolerance test, indicating improved glucose processing.
This was accompanied by a decrease in insulin levels at two hours, suggesting the body needed less insulin to control blood sugar. Of the 14 patients who had indeterminate or abnormal glucose tolerance at the start of the study, 13 improved after treatment, with 10 returning to normal glucose tolerance.
No participant progressed to CFRD on Trikafta. As expected, the treatment was also associated with better lung function and increases in weight and body mass index (a measure of body fat that takes into account weight and height) in both groups of patients.
These results support Trikafta’s “favourable metabolic effects beyond established respiratory benefits” and suggest that “screening and treatment guidelines may need to evolve to reflect a more dynamic understanding of glucose metabolism in CF,” the researchers wrote.
Among the study’s limitations, the scientists noted its relatively small number of patients, which may partly explain the lack of statistically significant differences in some analyses.
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