a National Research Institute , Los Angeles , CA , USA.
b Sanofi Germany , Frankfurt , Germany.
Curr Med Res Opin. 2019 Apr;35(4):689-695. doi: 10.1080/03007995.2018.1541316. Epub 2018 Dec 6.
To evaluate the lixisenatide dose range delivered by the iGlarLixi SoloSTAR pen (5-20 µg), alone or in fixed-ratio combination with insulin glargine (iGlar; iGlarLixi).
Data from three clinical studies were analyzed to assess lixisenatide efficacy and safety: a phase 2a trial assessing gastric emptying effects (ACT6011); a phase 2b dose-ranging trial (DRI6012); and a randomized controlled phase 3 trial comparing iGlarLixi with its components of iGlar and lixisenatide (LixiLan-O). Efficacy metrics included glycated hemoglobin A (A1C), post-prandial glucose (PPG) values following a standardized breakfast, fasting plasma glucose (FPG), and weight change. Occurrence of gastrointestinal adverse events was also assessed.
ACT6011: lixisenatide doses from 5-20 μg once daily (QD) suppressed PPG; maximal reductions in mean PPG area under the curve were achieved with doses ≥12.5 µg QD, but doses as low as 5 μg achieved 44% of maximal reduction. DRI6012: lixisenatide doses 5-20 μg QD resulted in significant, dose-dependent decreases in A1C, percentage of patients achieving A1C <7.0%, and 2-h PPG levels; doses of 20 μg achieved complete suppression of PPG. LixiLan-O: iGlarLixi decreased 2-h PPG across the entire dose range. Lixisenatide dose was unrelated to reductions in FPG with iGlarLixi. Similar reductions in A1C were seen with iGlarLixi across all lixisenatide doses.
This analysis demonstrates the clinical benefit of lixisenatide alone or in the formulation of iGlarLixi over the entire dose range of lixisenatide contained in iGlarLixi (5-20 µg), supporting the selection of the lixisenatide dose range delivered by the iGlarLixi SoloSTAR pen.
评估 ixersenatide 在 iGlarLixi SoloSTAR 笔（5-20μg）中的剂量范围，包括 ixersenatide 单药治疗和与甘精胰岛素（iGlar）的固定剂量联合治疗。
分析了三项临床研究的数据，以评估 ixersenatide 的疗效和安全性：一项评估胃排空作用的 2a 期试验（ACT6011）；一项 2b 期剂量范围研究（DRI6012）；以及一项比较 iGlarLixi 与其成分甘精胰岛素和 ixersenatide（LixiLan-O）的随机对照 3 期试验。疗效指标包括糖化血红蛋白 A（A1C）、标准化早餐后餐后血糖（PPG）值、空腹血糖（FPG）和体重变化。还评估了胃肠道不良事件的发生情况。
ACT6011：ixersenatide 剂量为 5-20μg 每日一次（QD）可抑制 PPG；剂量≥12.5μg QD 时可达到最大的平均 PPG 曲线下面积降低，但剂量低至 5μg 时可达到最大降低的 44%。DRI6012：ixersenatide 剂量为 5-20μg QD 可显著降低 A1C，降低 A1C＜7.0%的患者比例和 2 小时 PPG 水平，呈剂量依赖性；20μg 剂量可完全抑制 PPG。LixiLan-O：iGlarLixi 降低了整个剂量范围内的 2 小时 PPG。iGlarLixi 时，ixersenatide 剂量与 FPG 的降低无关。在所有 ixersenatide 剂量中，iGlarLixi 都观察到了相似的 A1C 降低。
这项分析证明了 ixersenatide 单药治疗或与 iGlarLixi 联合应用在 iGlarLixi 中 ixersenatide 全剂量范围内（5-20μg）的临床获益，支持了 iGlarLixi SoloSTAR 笔所提供的 ixersenatide 剂量范围的选择。
