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Current and Emerging Agents for the Treatment of Hypoglycemia in Patients with Congenital Hyperinsulinism

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Abstract

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycmia in neonatles and children. The inappropriate secretion of insulin by the pancreatic β-cells produces recurrent hypoglycemia, which can lead to severe and permanent brain damage. CHI results from mutations in different genes that play a role in the insulin secretion pathway, and each differs in their responsiveness to medical treatment. Currently, the only available approved treatment for hyperinsulinism is diazoxide. Patients unresponsive to diazoxide may benefit from specialized evaluation including genetic testing and 18F-DOPA PET to identify those with focal forms of CHI. The focal forms can be cured by selective pancreatectomy, but the management of diazoxide-unresponsive diffuse CHI is a real therapeutic challenge. Current off-label therapies include intravenous glucagon, octreotide and long-acting somatostatin analogs; however, they are often insufficient, and a 98% pancreatectomy or continuous feeds may be required. For the first time in over 40 years, new drugs are being developed, but none have made it to market yet. In this review, we will discuss current on-label and off-label drugs and review the currently available data on the novel drugs under development.

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Authors and Affiliations

  1. Division of Endocrinology, Instituto Nacional de Pediatria, Mexico City, Mexico

    Ana Paola De Cosio

  2. Cook Children’s Medical Center Congenital Hyperinsulinism Center, Fort Worth, TX, USA

    Paul Thornton

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  1. Ana Paola De Cosio
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Funding for the preparation of this manuscript was provided in part by the Cook Children’s Health Care System Endowed Chair program.

Conflict of interest

Paul Thornton has received consulting fees from Xeris Pharmaceuticals (the maker of stable liquid glucagon) and is a PI for both Xeris and Zealand in studies involving an investigational new drug for the treatment of congenital hyperinsulinism. Ana P. De Cosio has no conflict of interest to declare.

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De Cosio, A.P., Thornton, P. Current and Emerging Agents for the Treatment of Hypoglycemia in Patients with Congenital Hyperinsulinism. Pediatr Drugs 21, 123–136 (2019). https://doi.org/10.1007/s40272-019-00334-w

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