Background: Early treatment of neonatal diabetes with sulfonylureas has shown to improve neurodevelopment, beyond the demonstrated efficacy on glycemic control. Several barriers still prevent its use as an early treatment in preterm babies including the limited availability of a suitable galenic form of glibenclamide. Recently, an oral suspension of glibenclamide (Amglidia®) has been approved for use in EU.
Methods: We adopted Amglidia® 6mg/ml for the early treatment of neonatal diabetes due to an homozygous variant of KCNJ11 gene c.10C>T ; p.(Arg4Cys) in an extremely preterm infant. Amglidia® was administered via nasogastric tube and diluted in maternal milk at a final concentration of 1mg/1mL during the inpatient treatment, and administered orally at discharge.
Results: A female infant was born at 26+2 weeks’ gestation after C-section for chorioamnionitis (birthweight 750g (10thcentile)). On day 1 she presented with persistent hyperglycemia (>200mg/dL) and was started on insulin drip through a central catheter (0.01U/kg/h with an initial low glucose intake [4.5g/kg/d]) until day 41 of birth, when insulin was suspended for glucose normalization. On day 45 (32+5 weeks), due to a new raise of blood glucose (>400mg/dl) she was started on glibenclamide (Amglidia® 6 mg/mL) at the dose of 0.02mg/kg/day (in two daily administrations) via nasogastric tube. At 3 months of birth she was switched to oral Amglidia 0.6mg/ml at the dose of 0.008mg/kg/day with a progressive tapering off. The choice of glibenclamide suspension was due to the simplicity of drug administration and the possibility of the fine-tuning of dose titration. The patient exhibited a mean daily growth of 11g/kg/day during the treatment and glibenclamide was progressively weaned off and suspended at month 6 of birth (weight 4.9 kg [5th – 10th centile], M3 of corrected age). During the treatment, the patient exhibited a stable glucose profile within the range 4-8mmol/l in the absence of hypo or hyperglycemic episodes with 2-3 blood glucose tests per day. Retinopathy of prematurity (ROP) screening showed Stade 2 in ZoneII ROP at 32 weeks, with spontaneous regression at 45 weeks, while on glibenclamide.
Conclusion: This is the first report of the successful use of Amglidia® in an extremely preterm infant and supports the responsiveness of beta-cell to glibenclamide at this gestational age. Amglidia® was efficacious, safe and easy to administer enterally/orally and could be regarded as part of the treatment for hyperglycemia even in very preterm babies due to its beneficial effects on the metabolic and neurodevelopmental side.
15 Sep 2022 - 17 Sep 2022