Trikafta triggers diabetes remission in 4 CF patients: Report
Patients able to stop taking insulin about 1 year after starting on therapy
Treatment with Trikafta triggered diabetes remission in four people with cystic fibrosis (CF) at a center in Australia, with each of these patients experiencing complete resolution of CF-related diabetes, or CFRD, after starting on the approved triple therapy.
In all four cases, the patients were able to stop taking insulin and other diabetes medications a little over a year, on average, after starting the modulator therapy. None of the patients has needed to resume diabetes treatment to maintain normal blood sugar levels, according to the researchers.
“Here we present a case series of four adults with CF commenced on [Trikafta] who achieved diabetes remission,” the team wrote.
The cases were detailed in a letter to the editor titled “Diabetes remission in adults with cystic fibrosis commenced on Elexacaftor/Tezacaftor/Ivacaftor: A single center case-series,” which was published in the journal Pediatric Pulmonology,
All patients achieving disease remission were teens or young adults
Cystic fibrosis 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 dysfunction or absence of CFTR lead the body to make unusually thick and sticky mucus that builds up in organs, causing damage that drives most CF symptoms.
CFRD is a common complication of cystic fibrosis that occurs when mucus builds up in the pancreas, leading to a deficiency of the hormone insulin as well as insulin resistance — when cells don’t respond as they should to insulin. This ultimately results in high blood sugar, with patients diagnosed with CF-related diabetes.
Trikafta, which is widely approved for treating CF, contains a combination of three CFTR modulators (elexacaftor, tezacaftor, and ivacaftor) that can boost the functionality of the defective CFTR protein in people with cystic fibrosis caused by particular mutations. Modulators like Trikafta have revolutionized CF treatment, though most research on these meds has focused on how they affect lung health.
The cases in this report involved four teens and young adults, ages 16 to 25, who were treated with Trikafta at a center in Queensland. All of them carried at least one copy of F508del, the most common CF-causing mutation.
In our single-center case series, we present a detailed report of four adults with pre-existing CF-related diabetes who ceased insulin following [Trikafta] initiation due to hypoglycemia and achieved diabetes remission.
Prior to starting on Trikafta, all four patients had been diagnosed with CFRD, which they were managing with insulin. In all four cases, blood sugar tests after starting on Trikafta revealed abnormally low blood sugar, known as hypoglycemia — the exact opposite of what’s usually the problem in CFRD. This eventually led all four of them to stop diabetes treatment, and none had needed to restart it at the time this study was concluded.
“In our single-center case series, we present a detailed report of four adults with pre-existing CF-related diabetes who ceased insulin following [Trikafta] initiation due to hypoglycemia and achieved diabetes remission,” the researchers wrote.
The findings imply that, at least in some cases, Trikafta may be able to rescue pancreas function to effectively reverse CFRD. The researchers speculated that this might be more likely in younger patients with less advanced diabetes, but they stressed that additional studies will be needed to know for sure.
The team also emphasized a need for long-term follow-up for these patients to see whether Trikafta can further restore and/or maintain normal pancreas function in these CF patients.
Spurred by this finding, the researchers said they have launched a comprehensive study of adults on Trikafta who show similar characteristics to what was seen here, so as to learn more.
Trikafta is sold by Vertex Pharmaceuticals, which was not involved with this study.
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