Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
Department of Endocrinology and Metabolism, General Hospital of Beijing Military Region, Beijing, China.
Diabetes Obes Metab. 2020 Dec;22(12):2375-2383. doi: 10.1111/dom.14163. Epub 2020 Sep 6.
To assess the efficacy and safety of polyethylene glycol loxenatide (PEX168), a new glucagon-like peptide-1 receptor agonist, as an add-on to metformin therapy in Chinese patients with type 2 diabetes (T2D).
This was a multicentre, randomized, double-blind, placebo-controlled phase 3b trial. After metformin monotherapy (≥1500 mg/day) for 8 weeks or more, patients with uncontrolled T2D (HbA1c of 7.0%-10.5%) from 44 sites were randomized (1:1:1) to metformin + placebo, metformin + PEX168 100 μg, and metformin + PEX168 200 μg. The core treatment period lasted for 24 weeks, followed by a 28-week extension period. The primary endpoint was the change in HbA1c levels at week 24. The main secondary endpoint was the proportion of patients with an HbA1c of less than 7.0% at week 24.
The least-square mean (standard error) change in HbA1c levels was significantly greater (P < .001 for superiority) in the PEX168 groups (-1.16% [0.08%] and -1.14% [0.08%] with 100 and 200 μg, respectively) than in the placebo group (0.35% [0.08%]). The proportion of patients with an HbA1c of less than 7.0% at week 24 was significantly higher in the PEX168 100 μg (37.4%) and PEX168 200 μg (40.6%) groups than in the placebo group (16.8%; both P < .001). The gastrointestinal reactions were mild; the risks of hypoglycaemia and weight gain did not increase. Anti-PEX168 antibodies were noted in less than 2% of patients. No treatment-emergent serious adverse events occurred.
The subcutaneous injection of PEX168 once a week can effectively, continuously and safely improve HbA1c levels in patients with T2D when combined with metformin.
评估聚乙二醇洛塞那肽（PEX168）作为一种新型胰高血糖素样肽-1 受体激动剂，在接受二甲双胍治疗的中国 2 型糖尿病（T2D）患者中的疗效和安全性。
这是一项多中心、随机、双盲、安慰剂对照的 3b 期临床试验。在接受二甲双胍单药治疗（≥1500mg/天）8 周或更长时间后，来自 44 个中心的未得到控制的 T2D 患者（HbA1c 为 7.0%-10.5%）按 1:1:1 的比例随机分配至二甲双胍+安慰剂、二甲双胍+PEX168 100μg 和二甲双胍+PEX168 200μg。核心治疗期持续 24 周，随后是 28 周的扩展期。主要终点为第 24 周时 HbA1c 水平的变化。主要次要终点为第 24 周时 HbA1c 水平小于 7.0%的患者比例。
PEX168 组的 HbA1c 水平变化的最小二乘均值（标准误差）显著更大（PEX168 组均<.001，具有优越性）（分别为-1.16%[0.08%]和-1.14%[0.08%]，分别使用 100μg 和 200μg），而安慰剂组为 0.35%[0.08%]。第 24 周时 HbA1c 水平小于 7.0%的患者比例在 PEX168 100μg（37.4%）和 PEX168 200μg（40.6%）组显著高于安慰剂组（16.8%；均<.001）。胃肠道反应轻微；低血糖和体重增加的风险没有增加。不到 2%的患者出现抗 PEX168 抗体。未发生治疗相关的严重不良事件。
每周皮下注射 PEX168 一次可有效、持续和安全地改善接受二甲双胍治疗的 T2D 患者的 HbA1c 水平。
