University of Tübingen, Tübingen, Germany.
University of Tennessee Health Science Center, Memphis, Tennessee.
Diabetes Obes Metab. 2018 Feb;20(2):409-418. doi: 10.1111/dom.13086. Epub 2017 Oct 5.
To evaluate the efficacy and safety of dulaglutide 1.5 and 0.75 mg in patients with type 2 diabetes by subgroups of gender, duration of diabetes and baseline glycated haemoglobin (HbA1c) in the dulaglutide clinical development programme (AWARD-1 to -6 and -8 clinical trials).
Change in HbA1c was analysed by gender, duration of diabetes (<5, ≥5 years and <10, ≥10 years), and baseline HbA1c (<8.5%, ≥8.5%) in pooled and individual studies. Changes from baseline in weight, hypoglycaemia and gastrointestinal adverse events were evaluated for individual trials.
In the pooled analysis of patients treated with dulaglutide 1.5 mg at 6 months, the reductions in HbA1c from baseline were similar across gender (men: least squares [LS] mean -1.26% [95% confidence interval {CI} -1.36, -1.16]; women: LS mean -1.33% [95% CI -1.43, -1.24]) and among duration of diabetes subgroups (<5 years: LS mean -1.32% [95% CI -1.43, -1.22]; ≥5 and <10 years: LS mean -1.33% [95% CI -1.43, -1.22]; ≥10 years: -1.24% [95% CI -1.35, -1.14]). Patients with baseline HbA1c ≥8.5% had greater HbA1c reductions than patients with baseline HbA1c <8.5%, (≥8.5%: LS mean -1.86% [95% CI -1.97, -1.75]; <8.5%: LS mean -1.02% [95% CI -1.12, -0.93]). Reductions in fasting blood glucose (FBG) were consistent with HbA1c changes. Similar results were observed with dulaglutide 0.75 mg. In general, body weight changes were similar among duration of diabetes and in baseline HbA1c subgroups, respectively; women had a numerically greater weight loss or less weight gain than men with both dulaglutide doses. There was no clinically meaningful difference in hypoglycaemia trends by gender or duration of diabetes. Hypoglycaemia incidence and rate were generally lower in patients with baseline HbA1c ≥8.5% than in those with <8.5%, except for the AWARD-4 study (combination with mealtime insulin).
Across the AWARD studies, dulaglutide demonstrated significant improvements in glycaemic control irrespective of gender, duration of diabetes, or baseline HbA1c, with greater HbA1c and FBG reductions in patients with a higher baseline HbA1c. Dulaglutide was well tolerated, with a safety profile similar to other glucagon-like peptide-1 receptor agonists.
评估在糖尿病 2 型患者中，利拉鲁肽 1.5 和 0.75mg 的疗效和安全性，根据性别、糖尿病病程和基线糖化血红蛋白（HbA1c）对来自利拉鲁肽临床开发项目（AWARD-1 至 -6 和 -8 临床试验）的亚组进行分析。
在汇总和个体研究中，根据性别、糖尿病病程（<5 年、≥5 年和<10 年、≥10 年）以及基线 HbA1c（<8.5%、≥8.5%）分析 HbA1c 的变化。对个体试验中体重、低血糖和胃肠道不良事件的变化进行评估。
在接受利拉鲁肽 1.5mg 治疗 6 个月的患者的汇总分析中，性别之间（男性：最小二乘[LS]均值-1.26%[95%置信区间{CI}：-1.36，-1.16]；女性：LS 均值-1.33%[95%CI：-1.43，-1.24]）和糖尿病病程亚组中（<5 年：LS 均值-1.32%[95%CI：-1.43，-1.22]；≥5 年且<10 年：LS 均值-1.33%[95%CI：-1.43，-1.22]；≥10 年：LS 均值-1.24%[95%CI：-1.35，-1.14]），从基线的 HbA1c 降低情况相似。与基线 HbA1c<8.5%的患者相比，基线 HbA1c≥8.5%的患者 HbA1c 降低幅度更大（≥8.5%：LS 均值-1.86%[95%CI：-1.97，-1.75]；<8.5%：LS 均值-1.02%[95%CI：-1.12，-0.93]）。空腹血糖（FBG）的降低与 HbA1c 的变化一致。利拉鲁肽 0.75mg 也观察到了类似的结果。一般来说，糖尿病病程和基线 HbA1c 亚组之间的体重变化相似；与男性相比，女性分别有更大的体重减轻或更少的体重增加，这两种剂量的利拉鲁肽均如此。性别或糖尿病病程对低血糖趋势无明显影响。除了 AWARD-4 研究（与餐时胰岛素联合使用）之外，基线 HbA1c≥8.5%的患者低血糖发生率和发生率通常低于<8.5%的患者。
在 AWARD 研究中，无论性别、糖尿病病程或基线 HbA1c 如何，利拉鲁肽均能显著改善血糖控制，HbA1c 和 FBG 降低幅度在基线 HbA1c 较高的患者中更大。利拉鲁肽具有良好的耐受性，安全性与其他胰高血糖素样肽-1 受体激动剂相似。
