Diva D De León, Indraneel Banerjee, Sebastian Kummer, Sune Birch, Eva Bøge, Jelena Ivkovic, David M Kendall, Paul S Thornton
{"title":"Dasiglucagon in Children with Congenital Hyperinsulinism up to 1 Year of Age: Results from a Randomized Clinical Trial.","authors":"Diva D De León, Indraneel Banerjee, Sebastian Kummer, Sune Birch, Eva Bøge, Jelena Ivkovic, David M Kendall, Paul S Thornton","doi":"10.1210/clinem/dgae818","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>Congenital hyperinsulinism (CHI) is a cause of persistent hypoglycemia in childhood with considerable risk of lifelong neurological sequelae. Available pharmacological therapies are limited. Dasiglucagon is a glucagon analog for the treatment of hypoglycemia.</p><p><strong>Objective: </strong>To assess efficacy and safety of dasiglucagon in children with CHI up to 1 year of age.</p><p><strong>Methods: </strong>This study included a randomized, crossover, double-blind, placebo-controlled Part 1, and an open-label, single-arm Part 2 at four centers in Germany, UK, and USA. Participants comprised children with CHI aged 7 days to 12 months who were dependent on IV glucose. In Part 1, participants were randomized to dasiglucagon or placebo for 48 hours, then crossed over to the other treatment for 48 hours. In Part 2, all participants received dasiglucagon for 21 days. The primary outcome was mean IV glucose infusion rate (GIR) in the last 12 hours of Part 1.</p><p><strong>Results: </strong>Between 6/19/2020 and 2/9/2022, 12 eligible participants were randomized to dasiglucagon-placebo (n = 7) or placebo-dasiglucagon (n = 5). The IV GIR was significantly reduced with dasiglucagon compared with placebo (least-squares mean 4.3 mg/kg/min [95% confidence interval [CI], 1.04 to 7.60 mg/kg/min] and 9.5 mg/kg/min [95% CI, 6.24 to 12.81 mg/kg/min], respectively; P = .004). The most frequent adverse events in both treatment groups were gastrointestinal, dermatological, and metabolism and nutritional disorders.</p><p><strong>Conclusion: </strong>In infants with CHI, dasiglucagon significantly reduced the amount of IV glucose needed to maintain euglycemia compared with placebo. Dasiglucagon represents a promising treatment for the management of CHI.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Endocrinology & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1210/clinem/dgae818","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Context: Congenital hyperinsulinism (CHI) is a cause of persistent hypoglycemia in childhood with considerable risk of lifelong neurological sequelae. Available pharmacological therapies are limited. Dasiglucagon is a glucagon analog for the treatment of hypoglycemia.
Objective: To assess efficacy and safety of dasiglucagon in children with CHI up to 1 year of age.
Methods: This study included a randomized, crossover, double-blind, placebo-controlled Part 1, and an open-label, single-arm Part 2 at four centers in Germany, UK, and USA. Participants comprised children with CHI aged 7 days to 12 months who were dependent on IV glucose. In Part 1, participants were randomized to dasiglucagon or placebo for 48 hours, then crossed over to the other treatment for 48 hours. In Part 2, all participants received dasiglucagon for 21 days. The primary outcome was mean IV glucose infusion rate (GIR) in the last 12 hours of Part 1.
Results: Between 6/19/2020 and 2/9/2022, 12 eligible participants were randomized to dasiglucagon-placebo (n = 7) or placebo-dasiglucagon (n = 5). The IV GIR was significantly reduced with dasiglucagon compared with placebo (least-squares mean 4.3 mg/kg/min [95% confidence interval [CI], 1.04 to 7.60 mg/kg/min] and 9.5 mg/kg/min [95% CI, 6.24 to 12.81 mg/kg/min], respectively; P = .004). The most frequent adverse events in both treatment groups were gastrointestinal, dermatological, and metabolism and nutritional disorders.
Conclusion: In infants with CHI, dasiglucagon significantly reduced the amount of IV glucose needed to maintain euglycemia compared with placebo. Dasiglucagon represents a promising treatment for the management of CHI.
期刊介绍:
The Journal of Clinical Endocrinology & Metabolism is the world"s leading peer-reviewed journal for endocrine clinical research and cutting edge clinical practice reviews. Each issue provides the latest in-depth coverage of new developments enhancing our understanding, diagnosis and treatment of endocrine and metabolic disorders. Regular features of special interest to endocrine consultants include clinical trials, clinical reviews, clinical practice guidelines, case seminars, and controversies in clinical endocrinology, as well as original reports of the most important advances in patient-oriented endocrine and metabolic research. According to the latest Thomson Reuters Journal Citation Report, JCE&M articles were cited 64,185 times in 2008.