Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
Eli Lilly and Company, Indianapolis, Indiana.
Diabetes Obes Metab. 2019 Nov;21(11):2570-2575. doi: 10.1111/dom.13844. Epub 2019 Aug 16.
The long-acting glucagon-like peptide-1 receptor agonist dulaglutide acts by stimulating insulin secretion and reducing glucagon levels in a glucose-dependent manner both in the fasting and postprandial states, resulting in reductions of both fasting glucose (FG) and postprandial glucose (PPG). In contrast, the main mechanism of action of basal insulin is to reduce elevated FG by inhibiting hepatic glucose production. The aim of the present post hoc analysis of the phase 3 AWARD-2 trial was to investigate whether specific baseline glycaemic patterns respond differentially to dulaglutide compared to insulin glargine (glargine). We categorized participants into four subgroups based on prespecified glucose thresholds and their baseline FG and daily 2-hour mean PPG: low FG/low PPG; low FG/high PPG; high FG/low PPG; and high FG/high PPG. Changes in glycaemic measures in response to treatment with dulaglutide or glargine were evaluated in each subgroup. At 52 weeks, significant reductions from baseline in glycated haemoglobin (HbA1c) were observed in all subgroups with dulaglutide 1.5 mg and with glargine (all P < .05), except in patients with low FG/low PPG who received glargine. Greater HbA1c reductions were observed with dulaglutide 1.5 mg compared to glargine in all subgroups (all P ≤ .05), except in the low FG/high PPG subgroup.
长效胰高血糖素样肽-1 受体激动剂度拉鲁肽通过在空腹和餐后状态下以葡萄糖依赖的方式刺激胰岛素分泌和降低胰高血糖素水平来发挥作用,从而降低空腹血糖(FG)和餐后血糖(PPG)。相比之下,基础胰岛素的主要作用机制是通过抑制肝葡萄糖生成来降低升高的 FG。本次对 3 期 AWARD-2 试验的事后分析旨在研究与甘精胰岛素(glargine)相比,特定的基线血糖模式是否对度拉鲁肽有不同的反应。我们根据预设的血糖阈值以及基线 FG 和每日 2 小时平均 PPG 将参与者分为四个亚组:低 FG/低 PPG;低 FG/高 PPG;高 FG/低 PPG;和高 FG/高 PPG。在每个亚组中评估了度拉鲁肽或甘精胰岛素治疗对血糖测量值的变化。在 52 周时,所有接受度拉鲁肽 1.5mg 和甘精胰岛素治疗的亚组(均 P<.05)的糖化血红蛋白(HbA1c)均较基线显著降低,除了接受甘精胰岛素治疗的低 FG/低 PPG 患者。与甘精胰岛素相比,所有亚组(均 P≤.05)接受度拉鲁肽 1.5mg 治疗的 HbA1c 降低幅度更大,除了低 FG/高 PPG 亚组。