Low-dose diazoxide is safe and effective in infants with transient hyperinsulinism

Area of Science:

• Neonatology
• Pediatric Endocrinology
• Pharmacology

Background:

• Transient hyperinsulinism (THI) is a common cause of neonatal hypoglycemia beyond the first week of life.
• Current guidelines suggest diazoxide doses of 5-15 mg/kg/day for THI, balancing efficacy with potential adverse events.
• The effectiveness of lower diazoxide doses (<5 mg/kg/day) in THI requires further investigation.

Purpose of the Study:

• To evaluate the efficacy and safety of diazoxide doses below 5 mg/kg/day in treating neonatal transient hyperinsulinism (THI).
• To determine if lower starting doses of diazoxide can effectively manage THI while minimizing adverse events.

Main Methods:

• A retrospective study of 73 infants with THI treated with low-dose diazoxide (2-5 mg/kg/day) between October 2015 and February 2021.
• Infants were stratified into weight-based cohorts receiving starting doses of 2 mg/kg/day, 3 mg/kg/day, or 5 mg/kg/day.
• Data collected included diazoxide dosage, duration of treatment, need for dose increase, and adverse events.

Main Results:

• The mean effective diazoxide dose was 3 mg/kg/day, with doses <5 mg/kg/day proving effective in managing THI.
• Adverse events occurred in 18% of infants, primarily mild events like edema and hyponatremia; two infants had suspected necrotizing enterocolitis.
• Dose increases were required in 35% of infants, with higher rates in the lowest starting dose cohort.

Conclusions:

• Diazoxide doses below 5 mg/kg/day are effective for treating transient hyperinsulinism in neonates.
• Starting diazoxide at 2-3 mg/kg/day may offer a favorable balance between efficacy and safety, reducing the risk of adverse events.
• While the association with necrotizing enterocolitis warrants further study, lower-dose diazoxide appears safe and effective for THI.