Clinical and Experimental Endocrinology, University of Leuven, Leuven, Belgium.
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Diabetes Obes Metab. 2018 Aug;20(8):2023-2028. doi: 10.1111/dom.13313. Epub 2018 May 2.
Glucagon-like peptide-1 receptor agonists lower blood glucose in type 2 diabetes (T2D) partially through glucose-dependent stimulation of insulin secretion. The aim of this study was to investigate whether beta-cell function (as measured by HOMA2-%B) at baseline affects the glycaemic response to dulaglutide. Dulaglutide-treated patients from AWARD-1, AWARD-3 and AWARD-6 clinical studies were categorised based on their homeostatic model assessment of beta-cell function (HOMA2-%B) tertiles. Changes in glycaemic measures in response to treatment with once-weekly dulaglutide were evaluated in each HOMA2-%B tertile. Patients with low HOMA2-%B had higher baseline glycated haemoglobin (HbA1c), fasting and postprandial blood glucose, and longer duration of diabetes (P < .001, all) (mean low, middle and high tertiles with dulaglutide 1.5 mg: HOMAB-2%B, 31%, 58%, 109%; HbA1c, 8.7%, 7.7%, 7.3%, respectively). At 26 weeks, the low tertile experienced larger reductions in HbA1c compared to the high tertile with dulaglutide 1.5 mg (mean; -1.55% vs. -0.98% [-16.94 vs. -10.71 mmol/mol]). Differences between low and high tertiles disappeared when adjusted for baseline HbA1c (LSM; -1.00 vs. -1.18% [-10.93 vs. -12.90 mmol/mol]). Greater decreases in fasting blood glucose and greater increases in fasting C-peptide were observed in the low tertile. Similar increases in HOMA2-%B were observed in all tertiles. Dulaglutide demonstrated clinically relevant HbA1c reduction irrespective of estimated baseline beta-cell function.
胰高血糖素样肽-1 受体激动剂通过葡萄糖依赖性刺激胰岛素分泌降低 2 型糖尿病（T2D）患者的血糖。本研究旨在探讨基线时β细胞功能（通过 HOMA2-%B 测量）是否会影响度拉糖肽的血糖反应。根据稳态模型评估的β细胞功能（HOMA2-%B）三分位数，对 AWARD-1、AWARD-3 和 AWARD-6 临床研究中的度拉糖肽治疗患者进行分类。在每个 HOMA2-%B 三分位数中评估每周一次度拉糖肽治疗对血糖测量值的变化。HOMA2-%B 低值的患者基线糖化血红蛋白（HbA1c）、空腹和餐后血糖以及糖尿病病程较长（均 < .001）（HOMA2-%B 低值、中值和高值与度拉糖肽 1.5 mg 治疗时的平均水平：HOMA2-%B，31%、58%、109%；HbA1c，8.7%、7.7%、7.3%）。在 26 周时，与度拉糖肽 1.5 mg 治疗的高值三分位相比，低值三分位的 HbA1c 降幅更大（平均降幅-1.55%比-0.98%[-16.94 比-10.71 mmol/mol]）。当根据基线 HbA1c 进行调整时，低值与高值三分位之间的差异消失（LSM；-1.00 比-1.18%[-10.93 比-12.90 mmol/mol]）。低值三分位的空腹血糖下降更大，空腹 C 肽增加更大。所有三分位的 HOMA2-%B 均有相似的增加。无论估计的基线β细胞功能如何，度拉糖肽均能显著降低 HbA1c。
