格列鲁肽对短肠综合征患者肠道吸收和肠外支持的影响。

IF 2.6 Q3 NUTRITION & DIETETICS

Clinical nutrition ESPEN Pub Date : 2025-08-06 DOI:10.1016/j.clnesp.2025.08.006

Ismail Pinar , Thor Schütt Svane Nielsen , Lise Soldbro , Mark Krogh Hvistendahl , Mark Berner-Hansen , Palle Bekker Jeppesen

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引用次数: 0

摘要

背景与目的：格列帕鲁肽是一种长效胰高血糖素样肽2 （GLP-2）类似物，正在开发用于治疗短肠综合征（SBS）患者。GLP-2促进肠道适应和吸收。本研究评估了格列鲁肽在SBS患者24周内对肠道湿重和能量吸收的疗效，以及在第52周时对减少肠外支持（PS）和维持身体成分的影响。方法：在这项单中心、开放标签、3b期研究中，10例SBS- 8伴肠衰竭（SBS- if）和2例肠功能不全患者接受格列鲁肽10 mg，每周一次皮下注射。通过金标准代谢平衡研究评估肠道吸收。主要终点是肠道湿重吸收的绝对变化，而次要终点评估治疗24周后能量、电解质和常量营养素吸收的变化。其他终点包括治疗52周后PS使用、身体成分和安全性的变化。结果：第24周，大鼠肠道湿重吸收数值平均增加398 g/d (P=0.0585)，能量吸收数值平均增加1038 kJ/d （P=0.0215）。电解质和常量营养素的吸收有所改善。在第52周，平均PS体积减少800 mL/d (P=0.0106)，平均PS能量含量减少866 kJ/d （P=0.0103）。身体组成和体重保持稳定，格列鲁肽显示出可控的安全性。结论：接受格列鲁肽治疗的SBS患者表现出肠道湿重和能量吸收增加，从而使SBS- if患者的PS需求相应降低。格列帕鲁肽显示出良好的安全性，将其定位为SBS患者的有希望的治疗方法。临床试验：政府编号：NCT04991311；ClincalTrialsRegister。欧盟草案编号：2020-005194-27。

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Outcomes of glepaglutide on intestinal absorption and parenteral support in patients with short bowel syndrome

Background & aims

Glepaglutide, a long-acting glucagon-like peptide 2 (GLP-2) analog, is under development for the treatment of patients with short bowel syndrome (SBS). GLP-2 enhances intestinal adaptation and absorption. This study assessed glepaglutide in terms of its 24-week efficacy on intestinal wet weight and energy absorption, as well as its impact on reducing parenteral support (PS) and maintaining body composition at week 52 in patients with SBS.

Methods

In this single-center, open-label, phase 3b study, 10 patients with SBS - 8 with intestinal failure (SBS-IF) and 2 with intestinal insufficiency - received glepaglutide 10 mg once weekly via subcutaneous injection. Intestinal absorption was assessed by the gold-standard metabolic balance studies. The primary endpoint was absolute change in intestinal wet weight absorption, while secondary endpoints assessed changes in energy, electrolyte, and macronutrient absorption after 24 weeks of treatment. Additional endpoints included changes in PS use, body composition and safety after 52 weeks of treatment.

Results

At week 24, mean numerical increase in intestinal wet weight absorption was 398 g/day (P = 0.0585) and mean energy absorption 1038 kJ/day (P = 0.0215). Improvements occurred in electrolyte and macronutrient absorption. At week 52, mean PS volume was reduced by 800 mL/day (P = 0.0106) with a reduction in mean PS energy content of 866 kJ/day (P = 0.0103). Body composition and weight remained stable, and glepaglutide demonstrated a manageable safety profile.

Conclusion

Patients with SBS treated with glepaglutide demonstrated increased intestinal wet weight and energy absorption, allowing corresponding reductions in PS requirements in those with SBS-IF. Glepaglutide demonstrated a favorable safety profile, positioning it as a promising treatment for patients with SBS.

ClinicalTrials.gov no: NCT04991311; ClinicalTrialsRegister.eu EudraCT no: 2020-005194-27.

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来源期刊

Clinical nutrition ESPEN NUTRITION & DIETETICS-

CiteScore

4.90

自引率

3.30%

发文量

512

期刊介绍： Clinical Nutrition ESPEN is an electronic-only journal and is an official publication of the European Society for Clinical Nutrition and Metabolism (ESPEN). Nutrition and nutritional care have gained wide clinical and scientific interest during the past decades. The increasing knowledge of metabolic disturbances and nutritional assessment in chronic and acute diseases has stimulated rapid advances in design, development and clinical application of nutritional support. The aims of ESPEN are to encourage the rapid diffusion of knowledge and its application in the field of clinical nutrition and metabolism. Published bimonthly, Clinical Nutrition ESPEN focuses on publishing articles on the relationship between nutrition and disease in the setting of basic science and clinical practice. Clinical Nutrition ESPEN is available to all members of ESPEN and to all subscribers of Clinical Nutrition.