Scheen André J
a Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine , CHU Liege , Liège , Belgium.
b Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM) , University of Liège , Liège , Belgium.
Expert Opin Biol Ther. 2017 Apr;17(4):485-496. doi: 10.1080/14712598.2017.1296131. Epub 2017 Feb 28.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are injectable agents used for the treatment of hyperglycemia in type 2 diabetes. The interest for this pharmacological class is rising with the development of once weekly compounds and the demonstration of a potential reduction in cardiorenal outcomes. Areas covered: The paper describes the main pharmacokinetic/pharmacodynamic characteristics of dulaglutide, a new once-weekly GLP-1 RA. Dulaglutide was extensively investigated in the phase-3 AWARD program, which demonstrated its safety and efficacy when compared to placebo or active glucose-lowering agents in patients treated with diet alone, metformin or sulfonylurea monotherapy, oral dual therapies and basal insulin. In both Caucasian and Japanese patients, comparative trials showed better glucose control with dulaglutide, with a minimal risk of hypoglycemia and weight loss, but at the expense of an increased dropout rate due to side effects, mostly transient gastrointestinal disturbances. Dulaglutide proved its non-inferiority versus liraglutide and the safety and tolerance profile is similar to that of other GLP-1 RAs. Expert opinion: The once-weekly formulation and the combined positive effects on both glucose control and weight improves patient satisfaction despite nausea. Dulaglutide must prove its capacity to reduce cardiovascular and diabetic complications in the ongoing prospective REWIND trial.
胰高血糖素样肽-1受体激动剂(GLP-1 RAs)是用于治疗2型糖尿病高血糖的注射剂。随着每周一次给药化合物的开发以及心脏肾脏结局潜在降低的证实,这类药物的关注度正在上升。涵盖领域:本文描述了一种新型每周一次的GLP-1 RA——度拉糖肽的主要药代动力学/药效学特征。度拉糖肽在3期AWARD项目中进行了广泛研究,该项目表明,在仅接受饮食治疗、二甲双胍或磺脲类单药治疗、口服联合治疗以及基础胰岛素治疗的患者中,与安慰剂或活性降糖药物相比,度拉糖肽具有安全性和有效性。在白种人和日本患者中,对比试验均显示度拉糖肽能更好地控制血糖,低血糖风险和体重减轻风险最小,但代价是因副作用导致的停药率增加,主要是短暂的胃肠道不适。度拉糖肽已证明其与利拉鲁肽相比具有非劣效性,且安全性和耐受性与其他GLP-1 RAs相似。专家观点:尽管存在恶心情况,但每周一次的给药方案以及对血糖控制和体重的综合积极作用提高了患者满意度。度拉糖肽必须在正在进行的前瞻性REWIND试验中证明其降低心血管和糖尿病并发症的能力。