New study links Kaftrio treatment to lower insulin doses in CFRD
Glucose variability fell after 1 year, though HbA1c was unchanged
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Lower insulin doses and less blood sugar variability were observed one year after adults with cystic fibrosis-related diabetes (CFRD) started Kaftrio.
That’s according to results from the DIATRIM study (NCT06331000), a real-world, multicenter observational study conducted at 13 centers in France. Researchers retrospectively analyzed data from adults with CFRD who began Kaftrio, which is marketed as Trikafta in the U.S.
However, there were no significant changes in glycated hemoglobin (HbA1c), a measure of average blood sugar levels over the previous two to three months. Insulin is the hormone that allows glucose, or blood sugar, to move from the bloodstream into the body’s cells.
Researchers see lower insulin use after Kaftrio
These “findings showed a reduction in total … insulin doses with an improvement in glucose variability after [Kaftrio] treatment initiation, suggesting a modulation of glucose homeostasis … and the possibility to reduce the burden of CFRD in some patients,” the researchers wrote. Glucose homeostasis refers to the body’s ability to keep blood sugar levels within a healthy range.
The study, “Study of Insulin Treatment Modalities in Adults With Cystic Fibrosis-Related Diabetes After Elexacaftor-Tezacaftor-Ivacaftor Therapy,” was published in Clinical Therapeutics.
CF is caused by mutations in the gene that makes the CFTR protein, which helps regulate the movement of salt and water in and out of cells. When CFTR does not work properly, thick, sticky mucus builds up in organs such as the lungs and pancreas.
About half of people with CF develop CFRD, which has been linked to lower body weight, worsening lung function, and a higher risk of death.
Kaftrio, marketed by Vertex Pharmaceuticals, is a combination of three CFTR modulators — elexacaftor, tezacaftor, and ivacaftor — designed to improve the function of the faulty CFTR protein in people with certain mutations. While some studies have reported improved blood sugar control after Kaftrio treatment, its specific effects on insulin use in people with CFRD have not been fully understood.
Real-world study tracks adults with CFRD
To learn more, researchers in France conducted a retrospective real-world study involving 107 adults who had been living with CFRD for an average of 11.5 years. Their average age was 33.3 years. All had F508del mutations, the most common CF-causing mutation, in at least one CFTR gene copy. Most participants (60%) had previously been treated with other CFTR modulators before starting Kaftrio.
All but two participants had pancreatic insufficiency, a common CF complication in which thick mucus prevents digestive enzymes from reaching the intestines. Researchers collected data on diabetes treatment and continuous glucose monitoring (CGM) for one year before and up to two years after Kaftrio was started.
At the start of the study, 65% of participants were using multiple daily insulin injections. Of these, 32% used prandial (mealtime) or long-acting insulin alone, while 33% were on a basal-bolus regimen, which combines long-acting basal insulin with rapid-acting insulin at meals. Another 21% used an insulin pump, and 14% managed their diabetes with diet alone.
After one year of Kaftrio treatment, total insulin doses decreased significantly from 0.37 to 0.30 IU/kg/day. Bolus insulin doses also fell, from 0.27 to 0.17 IU/kg/day. Basal, or long-acting, insulin doses did not change significantly.
Among those who were initially managing CFRD with diet alone, about one-third began insulin therapy during follow-up. Meanwhile, 6.5% of participants who had been using insulin were able to stop it.
Glucose monitoring shows steadier blood sugar
Results from continuous glucose monitoring (CGM) — wearable devices that automatically track blood sugar levels — showed that both the proportion of time spent with low blood sugar (below 70 mg/dL) and overall glucose variability decreased significantly after one year of Kaftrio treatment. According to the researchers, “these findings indicate an improvement in glucose control in individuals with CFRD following [Kaftrio] therapy.” They added that blood sugar variability “is significant in CF–related diabetes and increases the risk of [low glucose].”
However, there were no significant differences in HbA1c levels. The researchers noted that in people with more advanced CF, like many in this study, HbA1c may not always accurately reflect blood sugar control.
After one year, participants’ weight and body mass index (BMI) increased significantly, which may reflect improved nutritional status. The proportion of patients needing at least one course of intravenous (into-the-vein) antibiotics per year fell significantly from 46% to 11%.
Lung function, measured by percent predicted forced expiratory volume in one second (ppFEV1), improved from 61.5% to 76.9%. This measure reflects how much air a person can forcefully exhale in one second compared with expected values for someone of the same age, sex, and height.
