CFTR modulators keep blood glucose under control: Study

CF patients with diabetes might need insulin dose adjustments

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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CFTR modulators may help control glucose (sugar) levels in the blood of people with cystic fibrosis (CF), according to researchers in Israel, who called for regular oral glucose tolerance testing to adjust insulin dosing in diabetes and keep glucose from dropping too low.

The study, “Long-Term therapy with CFTR modulators consistently improves glucose metabolism in adolescents and adults with cystic fibrosis,” was published in Respiratory Medicine.

In CF, damage to the pancreas impairs the release of insulin, a hormone that controls the levels of glucose in circulation by moving it from the blood into cells, where it’s used to produce energy. As a result, as many as half of people with CF develop diabetes.

CFTR modulators are medications that ease symptoms of CF, such as the common breathing problems, by addressing what causes CF. They also seem to help with problems outside the lungs, such as increasing the release of insulin from the pancreas.

To find out how well CFTR modulators may help control glucose levels in the long term, the researchers compared the results of oral glucose tolerance testing, which measures the body’s ability to dispose of a glucose load, before and after starting treatment.

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Adults, teens followed for 4 years

The study involved 15 adults and adolescents with CF, ages 13 to 37. Twelve had pancreatic insufficiency, which occurs when the thick mucus produced in CF prevents the pancreas from releasing enough digestive enzymes. As for specific CFTR modulators, 10 participants were treated with Trikafta, one with Orkambi, and four with Kalydeco.

Patients took their second oral glucose tolerance test a median of 25 months after starting treatment with CFTR modulators. On average, the time between one test and the next was 49.9 months, or just over four years.

Over that time, glucose levels measured two hours after drinking a sugary solution dropped significantly, falling from an average 159.7 milligrams per deciliter of blood to 130.4 milligrams per deciliter, indicating patients were able to better move glucose into cells.

Of the four patients who had been diagnosed with CF-related diabetes before starting CFTR modulators, two improved glucose tolerance or reached normal glucose tolerance. As a result, they were taken off insulin treatment.

Overall, six patients showed better control of glucose levels after treatment with CFTR modulators. Eight patients remained stable, and one experienced worsening glucose control and developed CF-related diabetes.

The findings suggest that CFTR modulators may slow worsening of glucose control over time. Because patients with diabetes may be on insulin, their doses may need to be adjusted to prevent hypoglycemia, or low glucose levels in the blood, the researchers said.

While coming from a small number of patients, “these findings indicate the need for periodic [oral glucose tolerance testing] following the initiation of [CFTR modulator] therapy to appropriately adjust insulin requirements and prevent hypoglycemia,” the researchers wrote.

Clinical care guidelines from the CF Foundation recommend that patients take an oral glucose tolerance test every year, starting at the age of 10, to find out if they have abnormal glucose tolerance.