Efficacy and safety of octreotide for the treatment of congenital hyperinsulinism: a prospective, open-label clinical trial and an observational study in Japan using a nationwide registry

Abstract

Octreotide, a long-acting somatostatin analog, has been used for treating hypoglycemia caused by congenital hyperinsulinism (CHI). However, octreotide has not been evaluated in clinical trials and has not been approved in any developed country. We aimed to test the efficacy and safety of octreotide for diazoxide-unresponsive CHI through a combination of a single-arm, open-label clinical trial (SCORCH study) and an observational study to collect data on the clinical course of patients treated off-label in Japan (SCORCH registry). In the SCORCH study, 5 patients were stabilized (blood glucose > 45 mg/dL) by hypertonic glucose infusion, and treated by continuous subcutaneous octreotide infusion at a dose of 5-25 μg/kg/day. Continuous blood glucose monitoring was performed between -24 and +48 hours. In 3 patients, a clinically meaningful rise in blood glucose was achieved and therapy was continued. The glucose infusion was gradually decreased and stopped after 5, 11, and 174 days, respectively. In one case, remission of CHI was reached after 606 days and octreotide was discontinued. The SCORCH registry included 19 diazoxide-unresponsive patients treated by subcutaneous octreotide, by continuous infusion or multiple daily injections. Of the 17 patients treated with hypertonic glucose infusion, the infusion rate was reduced after 4 weeks to less than 50% in 11 patients (64.7%) and stopped in 9 (52.9%). During the combined observation period of 695.4 patient-months in both studies, no severe adverse events related to octreotide were observed. In conclusion, subcutaneous octreotide injection was effective and well tolerated in the majority of patients with diazoxide-unresponsive CHI.

Efficacy and safety of octreotide treatment for diazoxide‐unresponsive congenital hyperinsulinism in China

“…Nevertheless, 84.0% of patients in our study maintained blood glucose > 2.8 mmol/L. The SCORCH prospective trial and observational registry study, reported by Hosokawa et al, revealed that 60% and 64.7% of patients with diazoxide‐unresponsive CHI exhibited GIR reduction > 50% at 4 weeks, respectively, the GIR was reduced by 10%–20% when fasting glucose was > 11.1 mmol/L on two consecutive occasions 15 . Our study combined blood glucose values and dextrose weaning as efficacy criteria to clarify the effectiveness of octreotide treatment.…”

“…The SCORCH prospective trial and observational registry study, reported by Hosokawa et al, revealed that 60% and 64.7% of patients with diazoxide-unresponsive CHI exhibited GIR reduction > 50% at 4 weeks, respectively, the GIR was reduced by 10%-20% when fasting glucose was > 11.1 mmol/L on two consecutive occasions. 15 Our study combined blood glucose values and dextrose weaning as efficacy criteria to clarify the effectiveness of octreotide treatment. Demirbilek et al 10 reported that octreotide treatment was also effective in post-surgery patients who underwent near total pancreatectomy (14 patients) and focal resection (two patients).…”

Nationwide survey of endogenous hyperinsulinemic hypoglycemia in Japan (2017–2018): Congenital hyperinsulinism, insulinoma, non‐insulinoma pancreatogenous hypoglycemia syndrome and insulin autoimmune syndrome (Hirata’s disease)

“…In Japan, the pre‐emptive identification of the focal form of adenosine triphosphate‐sensitive potassium channel CHI by fluorine‐18‐l‐dihydroxyphenylalanine positron emission tomography followed by local surgical resection was first reported in 2009, and has gradually become the standard management. With the progress in the diagnosis of focal CHI, more aggressive medical treatments of diazoxide‐unresponsive CHI using continuous octreotide infusion and/or enteral nutrition using gastrostomy or nasogastric feeding have also become the standard care (management flowchart available in Yorifuji et al …”

Congenital Hyperinsulinism: Diagnosis and Treatment Update

“…Thus dose adjustment may be required ( 32 , 113 , 114 ). Although various side effects have been reported in case reports, in a study evalutaing the long-term safety and efficacy of octreotide in a large series of CHI patients, it was found to be a safe and effective treatment for diazoxide unresponsive CHI patients ( 102 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 ) ( Table 3 ). The effect of octreotide on linear growth have been found clinically insignificant ( 102 , 117 , 123 ).…”