Dasiglucagon for the Treatment of Congenital Hyperinsulinism: A Randomized Phase 3 Trial in Infants and Children

Paul S. Thornton, Diva D. De Leon, Susann Empting, David Zangen, David M. Kendall, Sune Birch, Eva Bøge, Jelena Ivkovic, Indraneel Banerjee

Research output: Contribution to journalArticlepeer-review

Abstract

CONTEXT: Congenital hyperinsulinism (CHI) is characterized by dysregulated insulin secretion causing hypoglycemia and consequent brain damage. Dasiglucagon is a glucagon analogue under investigation to treat CHI. OBJECTIVE: To evaluate the efficacy and safety of dasiglucagon delivered via continuous subcutaneous infusion to children with CHI and persistent hypoglycemia as add-on to standard of care (SoC). METHODS: In this open-label trial, patients were randomized 1:1 to SoC or SoC + dasiglucagon (10-70 µg/h) for 4 weeks. In the following 4 weeks, all patients received dasiglucagon + SoC. Hypoglycemia was assessed by self-monitored plasma glucose (SMPG) and blinded continuous glucose monitoring (CGM). Primary endpoint was average number of SMPG-detected hypoglycemia episodes/week (SMPG <3.9 mmol/L) during Weeks 2 to 4. RESULTS: Thirty-two patients (0.6-10.9 years) were randomly assigned to dasiglucagon + SoC (n = 16) or SoC (n = 16). The rate of SMPG-detected hypoglycemia decreased from baseline in both groups, but with no statistically significant difference during Weeks 2 to 4 (event rate ratio: 0.85 [0.54; 1.36], P = .5028). However, dasiglucagon administration resulted in a 43% reduction in CGM-detected hypoglycemia (<3.9 mmol/L) vs SoC alone during Weeks 2 to 4 (post hoc analysis; event rate ratio: 0.57 [0.39; 0.83], P = .0029). Dasiglucagon enabled reductions (of 37% to 61%) in all other measures of hypoglycemia assessed by CGM vs SoC alone including extent and percent time in hypoglycemia (post hoc analyses). Dasiglucagon appeared safe and well tolerated. Skin and gastrointestinal events were more frequent with dasiglucagon + SoC than SoC only. CONCLUSION: Clinically meaningful reductions in all CGM-recorded measures of hypoglycemia support using dasiglucagon as a potential treatment for CHI.

Original languageAmerican English
Pages (from-to)1071-1079
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume109
Issue number4
DOIs
StatePublished - 15 Mar 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.

Keywords

  • congenital hyperinsulinism
  • dasiglucagon
  • hypoglycemia
  • treatment

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