The Use of Lanreotide in the Treatment of Congenital Hyperinsulinism

Abstract

Context Congenital hyperinsulinism (HI) results in severe, persistent hypoglycemia and is associated with high risk of neurodevelopmental deficits. Sixty percent of HI cases are unresponsive to diazoxide, the only FDA-approved drug. Somatostatin analogs are used off-label as second line treatment; the long-acting somatostatin analogue, lanreotide, has been used to treat HI over the past decade. Existing reports are limited to small case series. Objective To assess the effectiveness and safety of lanreotide in individuals with HI. Design Retrospective cohort study of individuals with HI treated with lanreotide between 2015-2020. Setting The Congenital Hyperinsulinism Center at The Children’s Hospital of Philadelphia. Patients Fifty-four individuals with hyperinsulinism treated with lanreotide. Main Outcome Measures Fasting duration with plasma glucose > 70 mg/dL; frequency of lanreotide-associated side effects. Results The median duration of lanreotide therapy was 28.7 months (2.8-64.5). Thirty-four patients (63%) had HI due to inactivating mutations of the ATP sensitive potassium channel (KATP-HI) and 39% had undergone a pancreatectomy. Of 52 patients receiving other HI therapies, 22 (42%) were able to discontinue other treatments and were managed on lanreotide alone. Fasting duration with plasma glucose >70 mg/dL was significantly longer during therapy with lanreotide compared to prior to lanreotide initiation (8.6 ± 6.5 vs 5.1 ± 4.7 hrs, P = 0.001). The most common side effects were subcutaneous nodules (26%) and gallstones (11%). Conclusions Lanreotide is a well-tolerated treatment for patients with HI. It results in a longer duration of fasting and a simplification of treatment regimens.

International Guidelines for the Diagnosis and Management of Hyperinsulinism

“…Second-Line Treatment for Infants with Hyperinsulinism Who Are Diazoxide-Unresponsive or Have Unacceptable Diazoxide Side Effects or Are Unable to Obtain Diazoxide [Grade 2⊕⊕○○] Short-or long-acting somatostatin analogs (SSA) used in patients with HI include octreotide [119,120], long-acting octreotide (octreotide LAR) [121,122], and lanreotide [122][123][124][125][126]. Octreotide has been used since the late 1980s as a long-term therapy for HI to avoid the need for pancreatectomy or in cases that could not be controlled following subtotal pancreatectomy [119,120,127,128,129].…”

Bridging the gaps: recent advances in diagnosis, care, and outcomes in congenital hyperinsulinism

“…Somatostatin analogues have long been used off-label as second-line treatment. Cuff et al recently reported on 54 children treated with lanreotide, the largest series to date [31 ▪ ]. They found lanreotide resulted in significantly longer fasting tolerance, compared to fasting tolerance prior to lanreotide initiation.…”

Congenital Hyperinsulinism: An Historical Perspective

“…Approximately 20 years later, Le Quan Sang [46] and Dalit Modan-Moses [47] reported the successful use of long-acting somatostatin analogs, octreotide LAR and lanreotide, respectively, for the treatment of HI, which allowed for the simplification of the treatment regimens with monthly dosing rather than multiple daily doses or continuous subcutaneous infusion. In the largest series to date, Diva D. De Leon and colleagues [48] reported significant improvements on glycemic control and fasting tolerance in children treated with lanreotide. While somatostatin analogs continue to be commonly used as second-line treatment of HI, this indication has not been approved by the FDA (USA).…”