Children with neonatal diabetes switched from glibenclamide tablets to an oral suspension sulfonylurea therapy for 4 months experienced only mild adverse effects and no changes in HbA1c or incidence of hyperglycemia or hypoglycemia, according to findings from a phase 2 study published in Pediatric Diabetes.
“Glibenclamide was developed as an oral suspension to meet the needs of infants and young children who are unable to swallow whole tablets and for children who require doses too low to be reliably achieved using tablets,” Jacques Beltrand, MD, PhD, of Necker-Enfants Malades Hospital in Paris, and colleagues wrote in the study background. “The results of this study show that the target patients, ie, those younger than 5 years, rated the oral suspension positively. In addition, their parents were satisfied or very satisfied with the administration method of the suspension and preferred it over the tablets.”
In a prospective, nonrandomized, single-center study, Beltrand and colleagues analyzed data from 10 children with neonatal diabetes who received glibenclamide tablets for 1 month followed by the oral suspension for 3 months (eight boys). The main baseline HbA1c for the cohort was 6.4%, and six children were aged 5 years or younger. Median duration of diabetes was 2.7 years, and median glibenclamide treatment time was 2.3 years. Researchers assessed acceptability of the therapy using hedonic scales and patient/parent questionnaires; effectiveness was evaluated using HbA1c assays and safety was based on incidence of hypoglycemia, hyperglycemia and other adverse events.
The median dosage of the oral suspension therapy was 0.13 mg/kg at month 2 and 0.12 mg/kg at month 4, given twice daily. Researchers observed no statistically significant changes between baseline and month 4 in HbA1c (median change, –0.4%; 95% CI, –1.3 to 0.5) or fructosamine (median change, –6 mol/L; 95% CI, –87 to 19). At study completion, six children had an HbA1c of at least 5.6%, and no children experienced a worsening of glycemic control. Median frequencies of hypoglycemia and hyperglycemia were less than 5% of routine blood glucose assays and were similar with both drug formulations, according to researchers.
Two patients each experienced one episode of severe hypoglycemia ( 35 mg/dL), highlighting the need for dose titration when switching from tablets to suspension, the researchers noted. Researchers observed transient abdominal pain or diarrhea in three patients. No patients discontinued the treatment.
Researchers found that younger children (aged 5 years) preferred the oral suspension therapy vs. tablets, whereas older children preferred tablets vs. suspension.
“The glibenclamide oral suspension, which is the first antidiabetic drug specifically developed for pediatric patients, is acceptable, effective and safe in patients diagnosed with [neonatal diabetes] and their family,” the researchers wrote. “The availability of this suspension will allow a rapid and early switch to sulfonylurea therapy of all neonates and infants diagnosed with [neonatal diabetes] due to potassium channels mutation using the lowest effective dosage.” – by Regina Schaffer
Disclosures: One of the authors reports he is a scientific adviser for Ammtek Ltd.