Department of Pharmacy, Zhejiang Pharmaceutical College , Ningbo, Zhejiang, China.
Institute of Drug Discovery Technology, Ningbo University , Ningbo, Zhejiang, China.
Expert Opin Pharmacother. 2020 Aug;21(11):1311-1318. doi: 10.1080/14656566.2020.1747432. Epub 2020 Apr 8.
Hypoglycemia in diabetes is a common and unresolved complication during diabetes therapy, even life-threatening. Effective and convenient treatment for rescuing severe diabetic hypoglycemia and maintaining euglycemia is in high demand to reduce hypoglycemia-related morbidity and mortality. Dasiglucagon is a novel glucagon analog for diabetic hypoglycemia therapy.
This review summarizes the reported studies associated with the pharmacokinetics, pharmacodynamics, safety, and tolerability characteristics, as well as clinical application of dasiglucagon for managing diabetic hypoglycemia.
Dasiglucagon has demonstrated established solubility and stability in an aqueous formulation. Pharmacokinetics studies have shown dasiglucagon to exhibit higher absorption and a longer plasma elimination half-life than traditional reconstituted glucagon. Pharmacodynamic studies have shown that a full dose of 0.6 mg dasiglucagon could efficiently raise blood glucose level (BGL) by ≥20 mg/dL (9-10 min) from baseline following insulin-induced severe hypoglycemia in patients with type 1 diabetes, as well as rapidly increase BGL with small doses under euglycaemic and hypoglycemic conditions. Dasiglucagon is safe and well tolerated with the main adverse effects being nausea and vomiting. Collectively, dasiglucagon may be a promising candidate for severe diabetic hypoglycemic rescue and a continuous glycemic control in diabetic patients.
糖尿病患者的低血糖是糖尿病治疗过程中常见且未解决的并发症,甚至有生命危险。有效且方便的治疗方法可用于抢救严重糖尿病性低血糖并维持血糖正常,以降低与低血糖相关的发病率和死亡率。达格列净是一种用于治疗糖尿病性低血糖的新型胰高血糖素类似物。
本文综述了与达格列净治疗糖尿病性低血糖相关的药代动力学、药效学、安全性和耐受性特征,以及临床应用的研究报道。
达格列净在水性制剂中表现出稳定的溶解度。药代动力学研究表明,达格列净的吸收更快,血浆消除半衰期比传统重组成分的胰高血糖素更长。药效学研究表明,在 1 型糖尿病患者因胰岛素诱导的严重低血糖而接受 0.6mg 全剂量达格列净治疗后,其血糖水平(BGL)可在 9-10 分钟内从基线升高≥20mg/dL,在血糖正常和低血糖情况下,小剂量也能迅速升高 BGL。达格列净安全性和耐受性良好,主要不良反应为恶心和呕吐。总的来说,达格列净可能是抢救严重糖尿病性低血糖和控制糖尿病患者血糖的一种有前途的候选药物。