Department of Medical Gastroenterology and Hepatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
JPEN J Parenter Enteral Nutr. 2020 Nov;44(8):1535-1544. doi: 10.1002/jpen.1767. Epub 2020 Feb 5.
Patients with short bowel syndrome (SBS) and distal-bowel resections lack neuroendocrine feedback regulations, potentially resulting in rapid gastrointestinal (GI) transit. The objective was to assess the efficacy of glepaglutide, a long-acting glucagon-like peptide-2 analog, on GI transit in patients with SBS.
In this single-center, double-blind, dose-finding, phase 2 trial, patients with SBS were randomly assigned to 3 treatments (0.1, 1, and 10 mg) in a 2-period crossover design. Each treatment period included 3 weeks of daily, subcutaneous glepaglutide injections separated by a washout period of 4-8 weeks. Endpoints were changes from baseline and included scintigraphy, wireless motility capsule (WMC, SmartPill Given Imaging, Ltd, Yokneam, Israel), and paracetamol absorption test.
A total of 18 patients were randomized. In the 10-mg dose group (n = 9), glepaglutide significantly increased time to 10% gastric emptying (GE) of solids by 27 (4-50) minutes (adjusted mean [95% CI]), time to 50%GE of fluids by 40 (1-80) minutes, and time to 10% small bowel-emptying of solids by 21 (1-41) minutes. The WMC transit did not significantly change in any of the dose groups. The maximum paracetamol concentration significantly increased in the 10-mg dose group; however, the area under the curve remained the same.
The prolonged GI transit after glepaglutide treatment, along with demonstrated positive effects on intestinal mucosal growth and potential effects on GI hypersecretions, is believed to contribute to the observed beneficial effects on fecal output (primary endpoint) and associated improvement in intestinal absorption.
患有短肠综合征（SBS）和远端肠切除的患者缺乏神经内分泌反馈调节，可能导致胃肠道（GI）快速转运。目的是评估长效胰高血糖素样肽-2 类似物 glepaglutide 对 SBS 患者 GI 转运的疗效。
在这项单中心、双盲、剂量发现、2 期交叉试验中，SBS 患者以 2 期交叉设计随机分配至 3 种治疗（0.1、1 和 10mg）。每个治疗期包括 3 周的每日皮下 glepaglutide 注射，间隔 4-8 周洗脱期。终点为从基线的变化，包括闪烁扫描、无线动力胶囊（WMC，以色列 Yokneam 的 Given Imaging，Ltd.）和对乙酰氨基酚吸收试验。
共有 18 名患者被随机分配。在 10mg 剂量组（n=9）中，glepaglutide 使固体 10%胃排空（GE）时间显著增加 27（4-50）分钟（调整后的平均[95%CI]），使液体 50%GE 时间增加 40（1-80）分钟，使固体 10%小肠排空时间增加 21（1-41）分钟。任何剂量组的 WMC 转运均无显著变化。最大对乙酰氨基酚浓度在 10mg 剂量组显著增加；然而，曲线下面积保持不变。
glepaglutide 治疗后 GI 转运时间延长，同时对肠黏膜生长有明显的积极影响，并可能对 GI 高分泌有影响，这被认为有助于观察到对粪便排出量（主要终点）的有益影响，并改善肠吸收。
