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Oral therapy as safe, effective as insulin in cystic fibrosis-related diabetes

Patients with cystic fibrosis-related diabetes treated with oral repaglinide for 24 months experienced improvements in HbA1c and pulmonary function that were similar to those in patients treated with human insulin therapy, according to findings from an open-label, comparative intervention trial.

“If cystic-fibrosis-related diabetes is diagnosed, treatment guidelines recommend insulin therapy with multiple daily injections, although there are no data to assess whether this is the optimum treatment,” Manfred Ballmann, MD, of the pediatric clinic at University Medicine Rostock, Germany, and colleagues wrote in the study background. “Oral antidiabetic therapies might be as effective as insulin for some patients and could lessen the additional burden of care in patients already undergoing complex and demanding therapy.”

Ballmann and colleagues analyzed data from 71 patients with cystic fibrosis aged at least 10 years with a diagnosis of diabetes based on two consecutive oral glucose tolerance tests in the previous 6 months, attending one of 30 cystic fibrosis centers in Austria, France, Germany and Italy between March 2002 and December 2009. Researchers randomly assigned patients to oral repaglinide therapy at a maximum dose of 4 mg three times per day (n = 33; mean age, 22 years; 61% female; mean HbA1c, 6.4%) or multiple daily injections of regular human insulin (Actrapid HM, Novo Nordisk) three times per day 20 to 30 minutes before each meal (n = 41; mean age, 22 years; 22 girls and women; mean HbA1c, 6.6%) for a mean of 24 months. Patients attended follow-up visits every 3 months. Primary outcome was mean change in HbA1c from baseline to 24 months. Secondary outcomes included mean change in HbA1c from baseline to 12 months, mean changes in BMI z score, forced expiratory volume in 1 second (FEV) and forced vital capacity (FVC) from baseline to 12 and 24 months. Researchers used linear models to assess differences between groups.

Within the cohort, 30 patients in the repaglinide group and 37 in the insulin group were included in the primary analysis. Mean final daily dose of repaglinide was 2.6 mg per day; mean daily insulin dose was 18.6 IU per day.

At both 12 and 24 months, researchers observed no between-group differences for the proportion of patients with HbA1c 7% or less. The mean change from baseline to 24 months was 0.2% for patients in the repaglinide group and –0.2% for patients in the insulin group. Similarly, there were no between-group differences in pulmonary function at 12 and 24 months or in mean blood glucose concentration. Researchers observed a mean –0.7 change in BMI z score for both groups at 12 months that did not persist at 24 months.

The most frequent adverse events were pulmonary events, affecting 40% of patients in the repaglinide group and 45% of patients in the insulin group. There were no between-group differences in incidents of hypoglycemia (22 in each group). A portion of both groups discontinued study treatment before 24 months (14 in repaglinide group and 16 in the insulin group).

“Repaglinide represents an alternative treatment to insulin for patients with newly diagnosed asymptomatic cystic fibrosis-related diabetes,” the researchers wrote. “Treatment with an oral antidiabetic drug is less invasive than multiple daily injections, which might be particularly important for patients who already have a complex and demanding pharmaceutical therapy schedule that includes antibiotics, pancreatic enzymes, bronchodilators, and mucolytic agents, and additional supportive care. Treatment with an oral antidiabetic drug might reduce the treatment burden for patients and the care burden for their caregivers.” – by Regina Schaffer

Disclosures: ABCF Association, Mukoviszidose eV, Novo Nordisk and Vaincre la Mucoviscidose funded this study. One author reports he received personal fees from Vertex Pharmaceuticals.

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