OBJECTIVE Treatment of severe hypoglycemia outside of the hospital setting is limited to glucagon formulations requiring reconstitution before use, which may lead to erroneous or delayed glucagon administration. We compared the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and safety and tolerability of different doses of dasiglucagon, a novel soluble glucagon analog, with approved pediatric and full doses of GlucaGen in insulin-induced hypoglycemia in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS In this single-center, randomized, double-blind trial, 58 patients with type 1 diabetes received single subcutaneous injections of 0.1, 0.3, 0.6, or 1.0 mg dasiglucagon or 0.5 or 1.0 mg GlucaGen in a state of hypoglycemia (blood glucose target 55 mg/dL) induced by an intravenous insulin infusion.

RESULTS Dasiglucagon demonstrated a dose-dependent and rapid increase in plasma concentrations, reaching a maximum at ∼35 min with a half-life of ∼0.5 h. Dasiglucagon rapidly increased plasma glucose (PG) by ≥20 mg/dL (9–14 min) to PG ≥70 mg/dL (within 6–10 min), similar to GlucaGen, but with a longer-lasting and greater effect on PG. All patients on both treatments reached these end points within 30 min (predefined success criteria). Both treatments were well tolerated. Nausea was the most frequent adverse event, occurring at a similar rate (44–56%).

CONCLUSIONS Dasiglucagon was well tolerated and showed an early PD response similar to that of GlucaGen at corresponding doses, suggesting comparable clinical effects of the two glucagon formulations. Dasiglucagon has the potential to become an effective and reliable rescue treatment for severe hypoglycemia in a ready-to-use pen.

目的在医院范围以外治疗严重的低血糖仅限于在使用前需要重新配制的胰高血糖素制剂，这可能会导致错误或延迟的胰高血糖素给药。我们比较了不同剂量的dasiglucagon（一种新型的可溶性胰高血糖素类似物）与批准的儿科和全剂量GlucaGen在1型糖尿病患者胰岛素引起的低血糖中的药代动力学（PK）和药效学（PD）特性以及安全性和耐受性。

研究设计与方法在这项单中心，随机，双盲试验中，58例1型糖尿病患者在低血糖状态下接受了0.1、0.3、0.6或1.0 mg达西格列酮或0.5或1.0 mg GlucaGen的单次皮下注射（静脉注射胰岛素诱导的血糖目标值55 mg / dL）。

结果Dasiglucagon表现出剂量依赖性且血浆浓度快速增加，在〜35 min达到最大值，半衰期为〜0.5 h。与GlucaGen相似，达西格列酮可将血浆葡萄糖（PG）迅速增加≥20 mg / dL（9–14分钟）至PG≥70 mg / dL（6–10分钟内），但作用更持久，对PG的影响更大。两种疗法的所有患者均在30分钟内达到了这些终点（预定义的成功标准）。两种治疗均耐受良好。恶心是最常见的不良事件，发生率相似（44-56％）。

结论达斯古高冈具有良好的耐受性，并在相应剂量下显示出与GlucaGen相似的早期PD反应，表明这两种胰高血糖素制剂具有可比的临床效果。Dasiglucagon有可能成为即用笔治疗严重低血糖症的有效且可靠的抢救方法。