Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy.
Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
Diabetes Obes Metab. 2018 Jun;20(6):1490-1498. doi: 10.1111/dom.13237. Epub 2018 Feb 21.
Patients with a type-2-diabetes (T2D) phenotype positive for glutamic acid decarboxylase antibodies (GADA) represent the majority of cases of latent autoimmune diabetes of the adult (LADA). The GLP-1 receptor agonist dulaglutide, recently introduced for treatment of T2D, has yet to be evaluated in LADA patients. Our primary objective was to evaluate the effect of dulaglutide on glycaemic control (HbA1c) in GADA-positive LADA vs GADA-negative T2D patients.
A post-hoc analysis was performed using data from 3 randomized phase 3 trials (AWARD-2,-4,-5; patients with GADA assessment) which were part of the dulaglutide clinical development programme in T2D. LADA patients were identified by GADA ≥5 IU/mL (ELISA). Changes in HbA1c during 12 months of treatment with dulaglutide or comparator were analysed using mixed-effect model repeated measures.
Of 2466 adults tested for GADA (dulaglutide, 1710; glargine, 298; sitagliptin, 294; placebo, 164), 2278 (92.4%) were GADA-negative and 188 (7.6%) were GADA-positive, including 58 GADA-high patients (> 200 IU/mL) and 130 GADA-low patients (≤200 and ≥5 IU/mL). Overall, baseline parameters were comparable between the groups. Dulaglutide resulted in comparable HbA1c reductions in GADA-negative (LS mean change [95%CI], -1.09% [-1.15, -1.03]) and GADA-positive patients (-0.94% [-1.15, -0.72]) at 12 months. HbA1c reductions were numerically, but not statistically, significantly larger in GADA-low patients (-1.02% [-1.26, -0.78]) vs GADA-high patients (-0.72% [-1.21,-0.24]) at 12 months. Similar outcomes were observed at 3 and 6 months.
These data are the first to indicate that dulaglutide was effective in reducing HbA1c in LADA patients.
谷氨酸脱羧酶抗体（GADA）阳性的 2 型糖尿病（T2D）患者代表成人隐匿性自身免疫性糖尿病（LADA）的大多数病例。最近被引入用于治疗 T2D 的 GLP-1 受体激动剂度拉糖肽尚未在 LADA 患者中进行评估。我们的主要目的是评估度拉糖肽对 GADA 阳性 LADA 与 GADA 阴性 T2D 患者血糖控制（HbA1c）的影响。
对来自 3 项随机 3 期试验（AWARD-2、-4、-5；进行 GADA 评估）的事后分析，这些试验是度拉糖肽在 T2D 中的临床开发项目的一部分。通过 GADA≥5IU/ml（ELISA）确定 LADA 患者。使用混合效应模型重复测量分析在 12 个月的度拉糖肽或对照治疗期间 HbA1c 的变化。
在 2466 名接受 GADA 检测的成年人中（度拉糖肽 1710 名，甘精胰岛素 298 名，西格列汀 294 名，安慰剂 164 名），2278 名（92.4%）为 GADA 阴性，188 名（7.6%）为 GADA 阳性，其中 58 名为 GADA 高患者（>200IU/ml），130 名为 GADA 低患者（≤200 和≥5IU/ml）。总体而言，两组的基线参数相当。在 12 个月时，度拉糖肽在 GADA 阴性患者（LS 均值变化[95%CI]，-1.09%[-1.15，-1.03]）和 GADA 阳性患者（-0.94%[-1.15，-0.72]）中均导致 HbA1c 相当程度的降低。在 12 个月时，GADA 低患者（-1.02%[-1.26，-0.78]）的 HbA1c 降低幅度比 GADA 高患者（-0.72%[-1.21，-0.24]）大，但无统计学意义。在 3 个月和 6 个月时观察到类似的结果。
这些数据首次表明，度拉糖肽可有效降低 LADA 患者的 HbA1c。
