Congenital Hyperinsulinism Center, Cook Children's Medical Center, Fort Worth, TX 76104, USA.
Congenital Hyperinsulinism Center, Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
J Clin Endocrinol Metab. 2024 Mar 15;109(4):1071-1079. doi: 10.1210/clinem/dgad648.
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.
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).
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.
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.
Clinically meaningful reductions in all CGM-recorded measures of hypoglycemia support using dasiglucagon as a potential treatment for CHI.
先天性高胰岛素血症（CHI）的特征是胰岛素分泌失调导致低血糖和随之而来的脑损伤。Dasiglucagon 是一种正在研究用于治疗 CHI 的胰高血糖素类似物。
评估 dasiglucagon 通过连续皮下输注治疗伴有持续性低血糖的 CHI 儿童的疗效和安全性，作为标准治疗（SoC）的附加治疗。
在这项开放标签试验中，患者以 1:1 的比例随机分配至 SoC 或 SoC+dasiglucagon（10-70μg/h）治疗 4 周。在接下来的 4 周内，所有患者均接受 dasiglucagon+SoC 治疗。通过自我监测的血浆葡萄糖（SMPG）和盲法连续血糖监测（CGM）评估低血糖。主要终点是第 2 至 4 周内每周 SMPG 检测到的低血糖发作次数（SMPG<3.9mmol/L）的平均值。
32 名患者（0.6-10.9 岁）被随机分配至 dasiglucagon+SoC（n=16）或 SoC（n=16）组。两组的 SMPG 检测到的低血糖发生率均从基线下降，但在第 2 至 4 周内无统计学显著差异（事件发生率比：0.85[0.54；1.36]，P=0.5028）。然而，与单独使用 SoC 相比，dasiglucagon 治疗在第 2 至 4 周内使 CGM 检测到的低血糖（<3.9mmol/L）减少了 43%（事后分析；事件发生率比：0.57[0.39；0.83]，P=0.0029）。与单独使用 SoC 相比，CGM 评估的所有其他低血糖指标（包括低血糖的程度和时间百分比）均观察到 dasiglucagon 治疗后降低（37%-61%）（事后分析）。Dasiglucagon 似乎安全且耐受良好。与单独使用 SoC 相比，使用 dasiglucagon+SoC 时皮肤和胃肠道事件更频繁。
CGM 记录的所有低血糖指标均有临床意义的降低，支持使用 dasiglucagon 作为 CHI 的潜在治疗方法。
