Adjuvant Alpelisib Therapy for Congenital Hyperinsulinism

Congenital hyperinsulinism, often caused by mutations in ABCC8 or KCNJ11, leads to severe hypoglycemia and may require pancreatectomy. This correspondence reports the successful off-label use of alpelisib, a PI3K inhibitor, in a 4 month old infant with ABCC8 related hyperinsulinism unresponsive to conventional therapies (diazoxide, octreotide). Starting at 12.5 mg daily and titrated to 30 mg twice daily, alpelisib reduced time spent in hypoglycemia (<63 mg/dL) to 2% by week 13, enabling discontinuation of intravenous dextrose and transition to bolus feeding. Adverse effects included mild vomiting and elevated insulin levels. The findings suggest alpelisib may serve as an adjuvant therapy to avoid pancreatectomy, warranting further clinical trials.

Congenital hyperinsulinism, often caused by mutations in ABCC8 or KCNJ11, leads to severe hypoglycemia and may require pancreatectomy. This correspondence reports the successful off-label use of alpelisib, a PI3K inhibitor, in a 4 month old infant with ABCC8 related hyperinsulinism unresponsive to conventional therapies (diazoxide, octreotide). Starting at 12.5 mg daily and titrated to 30 mg twice daily, alpelisib reduced time spent in hypoglycemia (<63 mg/dL) to 2% by week 13, enabling discontinuation of intravenous dextrose and transition to bolus feeding. Adverse effects included mild vomiting and elevated insulin levels. The findings suggest alpelisib may serve as an adjuvant therapy to avoid pancreatectomy, warranting further clinical trials.