Apraglutide, a novel once-weekly glucagon-like peptide-2 analog, improves intestinal fluid and energy absorption in patients with short bowel syndrome: An open-label phase 1 and 2 metabolic balance trial.
Apraglutide, a novel once-weekly glucagon-like peptide-2 analog, improves intestinal fluid and energy absorption in patients with short bowel syndrome: An open-label phase 1 and 2 metabolic balance trial.
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DOI：
10.1002/jpen.2362
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发表时间：
2022-09
影响因子：
3.4
通讯作者：
Jeppesen, Palle B.
中科院分区：
文献类型：
--
作者：
Eliasson, Johanna;Hvistendahl, Mark K.;Freund, Nanna;Bolognani, Federico;Meyer, Christian;Jeppesen, Palle B.
关键词：
阿拉鲁肽是一种新型长效胰高血糖素样肽-2（GLP-2）类似物，设计用于每周一次皮下给药，有可能增加短肠综合征（SBS）伴肠功能不全（SBS-II）或肠衰竭（SBS-IF）患者残余肠道的液体和营养吸收。本试验研究了SBS-II和SBS-IF患者中阿拉鲁肽的安全性和对肠道吸收的影响。在这项开放标签、I期和II期试验中，粪便排出量≥1500 g/天的SBS-II（n = 4）或SBS-IF（n = 4）成人患者每周一次皮下注射5 mg阿拉鲁肽，持续4周。安全性是主要终点。次要终点包括通过住院患者代谢平衡研究测量的湿重（指示液体吸收）、电解质和能量（通过弹式量热法）的肠吸收相对于基线的变化。常见的治疗相关不良事件为胃肠道（GI）造口排出量减少（n = 6）、造口并发症（n = 6）、GI造口并发症（n = 5）、恶心（n = 5）、肠胃气胀（n = 4）、GI造口排出量异常（n = 4）、多尿（n = 3）和腹痛（n = 3）。唯一的治疗相关严重不良事件（1例患者发生）为腹痛。阿拉鲁肽显著增加湿重和能量吸收，校正均值分别为741 g/天（95% CI，194 - 1287; P = 0.015）和1095 kJ/天（95% CI，196 - 1994; P = 0.024）。钠和钾吸收显著增加，校正均值分别为38 mmol/d（95% CI，3 - 74; P = 0.039）和18 mmol/d（95% CI，4 - 32; P = 0.020）。SBS-II和SBS-IF患者对5 mg阿拉鲁肽每周一次给药耐受良好，并显著改善了液体、电解质和能量的吸收。
Apraglutide is a novel long‐acting glucagon‐like peptide‐2 (GLP‐2) analog designed for once‐weekly subcutaneous dosing, with the potential to increase fluid and nutrient absorption by the remnant intestine of patients who have short bowel syndrome (SBS) with intestinal insufficiency (SBS‐II) or intestinal failure (SBS‐IF). This trial investigated the safety and effects on intestinal absorption of apraglutide in patients with SBS‐II and SBS‐IF. In this open‐label, phase 1 and 2 trial, adult patients with SBS‐II (n = 4) or SBS‐IF (n = 4) and a fecal output of ≥1500 g/day received once‐weekly subcutaneous 5 mg apraglutide for 4 weeks. Safety was the primary end point. Secondary end points included change from baseline in intestinal absorption of wet weight (indicative of fluid absorption), electrolytes, and energy (by bomb calorimetry) measured by inpatient metabolic balance studies. Common treatment‐related adverse events were decreased gastrointestinal (GI) stoma output (n = 6), stoma complications (n = 6), GI stoma complications (n = 5), nausea (n = 5), flatulence (n = 4), abnormal GI stoma output (n = 4), polyuria (n = 3), and abdominal pain (n = 3). The only treatment‐related serious adverse event (experienced in one patient) was abdominal pain. Apraglutide significantly increased wet weight and energy absorption by an adjusted mean of 741 g/day (95% CI, 194 to 1287; P = 0.015) and 1095 kJ/day (95% CI, 196 to 1994; P = 0.024), respectively. Sodium and potassium absorption significantly increased by an adjusted mean of 38 mmol/day (95% CI, 3 to 74; P = 0.039) and 18 mmol/day (95% CI, 4 to 32; P = 0.020), respectively. Once‐weekly 5 mg apraglutide was well tolerated in patients with SBS‐II and SBS‐IF and significantly improved the absorption of fluids, electrolytes, and energy.
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影响因子：
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作者：
Bremholm, Lasse;Hornum, Mads;Jeppesen, Palle Bekker
通讯作者：
Jeppesen, Palle Bekker
影响因子：
29.4
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影响因子：
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24.5
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Cani PD;Possemiers S;Van de Wiele T;Guiot Y;Everard A;Rottier O;Geurts L;Naslain D;Neyrinck A;Lambert DM;Muccioli GG;Delzenne NM
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Delzenne NM
影响因子：
24.5
作者：
Jeppesen PB;Gilroy R;Pertkiewicz M;Allard JP;Messing B;O'Keefe SJ
通讯作者：
O'Keefe SJ