Introduction To evaluate the effects of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), on gastric emptying, glucose metabolism, and islet beta-cell function versus liraglutide and placebo in people with type 2 diabetes. Research design and methods This phase Ib study (ClinicalTrials.gov identifier: [NCT02059564][1]) randomized participants (n=47) to three cohorts. Within the first two cohorts, participants were randomized to placebo, efpeglenatide 6 mg weekly (QW; first cohort), or efpeglenatide 16 mg monthly (QM; second cohort). The third cohort received liraglutide 1.8 mg daily (QD). Gastric emptying was assessed through the pharmacokinetic (PK) profile of acetaminophen at baseline and steady state. Glucose metabolism and beta-cell function were assessed based on mixed-meal tolerance testing and a graded glucose infusion procedure. Results Treatment duration was approximately 3 months for efpeglenatide 16 mg QM and 1 month for efpeglenatide 6 mg QW and liraglutide. At peak drug concentrations, efpeglenatide 6 mg QW was non-inferior to liraglutide 1.8 mg QD in delaying gastric emptying, as assessed by acetaminophen PK (lower bound of 90% CI for the efpeglenatide:liraglutide ratio >0.8 for area under the curve (AUC)0–120, AUC0–180, AUC0–360 and maximum concentration (Cmax)). Efpeglenatide 16 mg QM did not decrease the rate of gastric emptying to as great an extent as liraglutide (ie, non-inferiority was not shown). Compared with liraglutide, both efpeglenatide dosing regimens demonstrated comparable or more favorable glucometabolic effects and improved beta-cell function. All gastrointestinal adverse events reported with efpeglenatide were mild or moderate in severity and transient over treatment and follow-up. Conclusions The glucometabolic effects of efpeglenatide 6 mg QW and 16 mg QM were comparable to liraglutide. Additional studies are necessary to further examine these benefits of efpeglenatide. Trial registration number [NCT02059564][1]. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02059564&atom=%2Fbmjdrc%2F9%2F1%2Fe002208.atom

中文翻译：

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efpeglenatide 与利拉鲁肽对 2 型糖尿病患者胃排空、葡萄糖代谢和 β 细胞功能的影响：一项探索性随机 Ib 期研究

简介 评估 efpeglenatide（一种长效胰高血糖素样肽 1 受体激动剂 (GLP-1 RA)）与利拉鲁肽和安慰剂相比对 2 型糖尿病患者胃排空、葡萄糖代谢和胰岛 β 细胞功能的影响. 研究设计和方法 该 Ib 期研究（ClinicalTrials.gov 标识符：[NCT02059564][1]）将参与者 (n=47) 随机分配到三个队列。在前两个队列中，参与者被随机分配到安慰剂组、每周 6 毫克 efpeglenatide（QW；第一队列）或每月 16 mg efpeglenatide（QM；第二队列）。第三组每天接受利拉鲁肽 1.8 mg (QD)。通过对乙酰氨基酚在基线和稳态时的药代动力学 (PK) 曲线评估胃排空。基于混合膳食耐受性测试和分级葡萄糖输注程序评估葡萄糖代谢和β细胞功能。结果 efpeglenatide 16 mg QM 的治疗持续时间约为 3 个月，efpeglenatide 6 mg QW 和利拉鲁肽的治疗持续时间约为 1 个月。在药物峰值浓度下，依格列肽 6 mg QW 在延迟胃排空方面不劣于利拉鲁肽 1.8 mg QD，如通过对乙酰氨基酚 PK 评估的（依格列肽：利拉鲁肽比值的 90% CI 下限 >0.8，曲线下面积（AUC） )0–120、AUC0–180、AUC0–360 和最大浓度 (Cmax)）。Efpeglenatide 16 mg QM 不会像利拉鲁肽那样降低胃排空率（即未显示非劣效性）。与利拉鲁肽相比，两种 efpeglenatide 给药方案都显示出相当或更有利的糖代谢作用和改善的 β 细胞功能。依格列那肽报告的所有胃肠道不良事件的严重程度均为轻度或中度，并且在治疗和随访期间是短暂的。结论 efpeglenatide 6 mg QW 和 16 mg QM 的糖代谢作用与利拉鲁肽相当。有必要进行额外的研究以进一步检查依格列肽的这些益处。试验注册号 [NCT02059564][1]。在当前研究期间生成和/或在当前研究期间分析的数据集可根据合理要求从相应作者处获得。[1]：/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02059564&atom=%2Fbmjdrc%2F9%2F1%2Fe002208.atom 依格列那肽报告的所有胃肠道不良事件的严重程度均为轻度或中度，并且在治疗和随访期间是短暂的。结论 efpeglenatide 6 mg QW 和 16 mg QM 的糖代谢作用与利拉鲁肽相当。有必要进行额外的研究以进一步检查依格列肽的这些益处。试验注册号 [NCT02059564][1]。在当前研究期间生成和/或在当前研究期间分析的数据集可根据合理要求从相应作者处获得。[1]：/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02059564&atom=%2Fbmjdrc%2F9%2F1%2Fe002208.atom 依格列那肽报告的所有胃肠道不良事件的严重程度均为轻度或中度，并且在治疗和随访期间是短暂的。结论 efpeglenatide 6 mg QW 和 16 mg QM 的糖代谢作用与利拉鲁肽相当。有必要进行额外的研究以进一步检查依格列肽的这些益处。试验注册号 [NCT02059564][1]。在当前研究期间生成和/或在当前研究期间分析的数据集可根据合理要求从相应作者处获得。[1]：/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02059564&atom=%2Fbmjdrc%2F9%2F1%2Fe002208.atom 有必要进行额外的研究以进一步检查依格列肽的这些益处。试验注册号 [NCT02059564][1]。在当前研究期间生成和/或在当前研究期间分析的数据集可根据合理要求从相应作者处获得。[1]：/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02059564&atom=%2Fbmjdrc%2F9%2F1%2Fe002208.atom 有必要进行额外的研究以进一步检查依格列肽的这些益处。试验注册号 [NCT02059564][1]。在当前研究期间生成和/或在当前研究期间分析的数据集可根据合理要求从相应作者处获得。[1]：/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02059564&atom=%2Fbmjdrc%2F9%2F1%2Fe002208.atom