Advances in Pharmacotherapy for Congenital Hyperinsulinism

Congenital hyperinsulinism (CHI) is a rare disorder causing persistent hypoglycaemia in infants due to excessive insulin secretion from pancreatic β-cells. It has genetic causes, primarily mutations in ATP-sensitive potassium channel genes (ABCC8, KCNJ11). CHI manifests in three forms—focal, diffuse, and atypical—distinguished by histology and genetics, influencing treatment strategies. Early diagnosis and tailored management are vital to prevent neurological damage. While transient CHI resolves spontaneously, permanent CHI often requires complex medical and/or surgical intervention. Despite advances, long-term neurodisability remains high, highlighting increased need to improve monitoring as well as better therapies with lesser side effects. Acute treatment aims to rapidly normalize glucose levels and long-term treatments include diazoxide (KATP channel agonist) to suppress insulin secretion, though its effectiveness depends on genetic mutation type. Other therapies include somatostatin analogues. Newer emerging therapies include novel glucagon analogues, monoclonal antibodies targeting insulin receptors, GLP-1 receptor antagonist, and selective somatostatin receptor agonist, currently under clinical trials. Along with medical treatment, children may require additional feeding support with carbohydrate supplementation using glucose polymers and special formulas. Continuous glucose monitoring aids detection but has limitations. Surgery is preferred for focal lesions to potentially cure CHI.