Randomised controlled trial of diazoxide for small for gestational age neonates with hyperinsulinaemic hypoglycaemia provided early hypoglycaemic control without adverse effects

Balachandran, Binesh; Mukhopadhyay, Kanya; Sachdeva, Naresh; Walia, Rama; Attri, Savita Verma

doi:10.1111/apa.14252

Cited by 15 publications

(16 citation statements)

References 22 publications

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“…One clinical trial was deemed eligible for inclusion. 8 Three additional clinical trials were identified in registries: 1 is ongoing (ANZCTR12620000129987); 1 was discontinued due to protocol compliance difficulties (NCT00994149); and 1 is of unknown status and remains unpublished (CTRI/2014/05/004617). The investigators of trial NCT00994149 were unable to provide any data.…”

Section: Search Resultsmentioning

confidence: 99%

“…The 1 included study by Balanchandran et al comprised 30 low birthweight (<2.5 kg) infants with hyperinsulinemic hypoglycemia (BGC <2.8 mmol/L with any detectable serum insulin) in the first 5 days after birth, who were randomized to either oral diazoxide capsules (9 mg/kg/day in 3 divided doses) or placebo capsules (cellulose powder). 8 If hypoglycemia persisted after 48 h, the dose was increased to 12 mg/kg/ day. Once euglycemia was achieved, the dose was tapered every 72 h. Oral feeds were started as soon as possible, initially at 30 mL/kg/day, and increased depending on tolerance and blood glucose stability, with glucose infusion rate decreased by protocol.…”

Section: Included Studiesmentioning

confidence: 99%

“…Early use of diazoxide is a possible treatment strategy for neonates that fail first-line management of hypoglycemia, such as buccal dextrose gel and feeding. 8 Importantly, diazoxide targets the underlying pathophysiology and directly promotes metabolic transition by slowing the secretion of insulin from the pancreatic β-cell. 9 By preventing exaggerated insulin release, diazoxide helps to promote glycogenolysis and gluconeogenesis, increasing hepatic glucose output, and lipolysis, which releases glycerol, a key substrate for gluconeogenesis, as well as free fatty acids for oxidative metabolism.…”

Section: Introductionmentioning

confidence: 99%

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Diazoxide for the Treatment of Transitional Neonatal Hypoglycemia: A Systematic Review

Laing

Hanning

Harding

et al. 2021

Journal of Neonatology

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Background: Neonatal hypoglycemia is widely recognized as a common, preventable cause of brain injury in infants. Early use of diazoxide, which attenuates insulin secretion, is a possible treatment strategy for neonates that fail first-line management of hypoglycemia. Objective: To systematically evaluate the effectiveness and safety of diazoxide compared to placebo or no diazoxide treatment for improving short- and long-term outcomes in neonates born at ≥35 weeks’ gestation who require treatment for transitional hypoglycemia. Methods: MEDLINE, SCOPUS, EMBASE, and Cochrane databases were searched from inception until November 2020. We included all published randomized and nonrandomized controlled studies of diazoxide therapy in neonates that reported 1 or more prespecified outcomes. We excluded studies that primarily reported on neonates born at <35 weeks, with congenital hyperinsulinism or inborn errors of metabolism, or who started treatment after 1 month of age. Two authors independently performed screening, risk of bias assessment, data extraction, and rating of evidence certainty (GRADE). Meta-analysis was performed in RevMan (inverse variance, fixed effects). Results: A total of 161 studies were screened, 7 reviewed in full, and 1 included (N = 30). Low-certainty evidence suggested that diazoxide, compared with placebo, is associated with a shorter duration of intravenous fluids (mean difference [MD] –50 h, 95% confidence interval [CI] −94, −6), decreased time to achieve full enteral feeding (MD –49 h, 95% CI −91, −7), and euglycemia (MD –33 h, 95% CI −66, −0). Conclusions: Diazoxide may promote metabolic transition in late preterm and term neonates with transitional hypoglycemia. Further high-quality randomized trials are needed to assess short- and long-term effects of diazoxide therapy.

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Section: Search Resultsmentioning

confidence: 99%

Section: Included Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Diazoxide for the Treatment of Transitional Neonatal Hypoglycemia: A Systematic Review

Laing

Hanning

Harding

et al. 2021

Journal of Neonatology

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“…Однако в ряде случаев высокая и длительно сохраняющаяся потребность в дотации углеводов или ее увеличение в динамике требуют назначения инсулино-статической терапии. Результаты крупного рандомизированного исследования, опубликованные в 2018 г., свидетельствуют о высокой эффективности диазоксида и его хорошей переносимости у маловесных пациентов с данным заболеванием [17].…”

Section: Discussionunclassified

Transient hyperinsulinism in neonates

Болмасова

Melikyan

Крылова

et al. 2020

Probl Endokrinol (Mosk)

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Congenital hyperinsulinusm is rare disease characterized high secretion of insulin by pancreatic beta cells leading to the development of hypoglycemia. Persistent and transient forms of hyperinsulinism are distinguished. Transient hyperinsulinism are the most common cause of severe hypoglycemia in newborns. The etiology of this disease is not known. There are risk factors for the development of transient hyperinsulinism: asphyxia at birth, prematurity, maternal diabetes, low or large weight by gestation. Hypoglycemia with hyperinsulinism is severe. Therefore, early diagnosis and therapy especially during the neonatal period, are necessary.The article describes 3 clinical cases of transient hyperinsulinism in children with different gestational age and concomitant pathology. All children recevied insulinostatic therapy with diazoxide with a positive effect: euglycemia without glucose requirement . In all children, therapy was completed subsequently. At the time of publication of the article, the physical and psychomotor development of children is normal.

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“…4,5 Hyperinsulinemic hypoglycemia (HH) is diagnosed by persistent hypoglycemia requiring a high glucose infusion rate (GIR) and inappropriately elevated insulin levels during hypoglycemia. [6][7][8][9] Diazoxide is the first-line and only US Food and Drug Administration-approved, pharmacologic treatment of refractory hyperinsulinism. Diazoxide targets pancreatic b cells, binding to the sulfonylurea receptor-1 subunit of the K ATP channel and inhibiting insulin release.…”

Section: Introductionmentioning

confidence: 99%

Necrotizing Enterocolitis in Neonates With Hyperinsulinemic Hypoglycemia Treated With Diazoxide

et al. 2021

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The most common cause of persistent hypoglycemia in the neonatal period is hyperinsulinism. Severe, refractory hypoglycemia resulting from hyperinsulinism can lead to significant brain injury and permanent cognitive disability. Diazoxide is the first-line and only US Food and Drug Administration–approved, pharmacologic treatment for refractory hyperinsulinism. In recent years, the use of diazoxide in neonates with persistent hyperinsulinemic hypoglycemia has increased in the United States. Known adverse effects of diazoxide include fluid retention, hypertrichosis, neutropenia, thrombocytopenia, and more recently, pulmonary hypertension. It is currently unknown if diazoxide exposure is associated with an increased risk of necrotizing enterocolitis (NEC) in neonates. We reviewed the cases of 24 patients in a level IV NICU at Massachusetts General Hospital who received diazoxide over 12 years (April 2006–April 2018). All 24 patients received enteral diazoxide for refractory hyperinsulinemic hypoglycemia. A total of 5 patients developed NEC after initiation of diazoxide based on clinical and radiographic findings, corresponding to 20% of infants exposed to diazoxide. This is above our baseline incidence of NEC (1% for all inborn infants and 6% for all inborn very low birth weight infants). More research and monitoring are necessary to characterize the potential risk of NEC associated with the use of diazoxide in the neonatal period.

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Randomised controlled trial of diazoxide for small for gestational age neonates with hyperinsulinaemic hypoglycaemia provided early hypoglycaemic control without adverse effects

Abstract: Using oral diazoxide for SGA neonates with HH provided early hypoglycaemic control with no apparent adverse effects.

Cited by 15 publications

References 22 publications

Diazoxide for the Treatment of Transitional Neonatal Hypoglycemia: A Systematic Review

Diazoxide for the Treatment of Transitional Neonatal Hypoglycemia: A Systematic Review

Transient hyperinsulinism in neonates

Necrotizing Enterocolitis in Neonates With Hyperinsulinemic Hypoglycemia Treated With Diazoxide

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