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An updated overview of glucagon-like peptide-2 analog trophic therapy for short bowel syndrome in adults.

ABSTRACT: Short bowel syndrome (SBS) is a clinical condition characterized by a failure to achieve optimal intestinal adaptation, which is necessary to maintain oral/enteral autonomy. At present, the treatment options for SBS are primarily intestinal replacement and rehabilitation. Intestinal rehabilitation mainly includes non-transplantation surgery and intestinal rehabilitation measures. In recent years, intestinal rehabilitation in patients with SBS using nutritional intestinal hormones, especially glucagon-like peptide-2 analogs, has made great progress. Many high-quality studies have provided evidence-based medical findings to support the development of clinical guidelines. This article reviews the latest research advancements regarding the use of glucagon-like peptide-2 analogs (teduglutide, glepaglutide, and apraglutide) in the treatment of SBS.

SUBMITTER: Zhu C

PROVIDER: S-EPMC8966062 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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An updated overview of glucagon-like peptide-2 analog trophic therapy for short bowel syndrome in adults.

Zhu Changzhen C Li Yuanxin Y

The Journal of international medical research 20220301 3

Short bowel syndrome (SBS) is a clinical condition characterized by a failure to achieve optimal intestinal adaptation, which is necessary to maintain oral/enteral autonomy. At present, the treatment options for SBS are primarily intestinal replacement and rehabilitation. Intestinal rehabilitation mainly includes non-transplantation surgery and intestinal rehabilitation measures. In recent years, intestinal rehabilitation in patients with SBS using nutritional intestinal hormones, especially glu ...[more]

PMID: 35343263

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Project description:Background and aimsGlucagon-like peptide 2 (GLP-2) may improve intestinal absorption in short bowel syndrome (SBS) patients with an end jejunostomy. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant GLP-2 analogue, prolongs the intestinotrophic properties of GLP-2 in animal models. The safety and effect of teduglutide were investigated in SBS patients with and without a colon in continuity.MethodsTeduglutide was given subcutaneously for 21 days once or twice daily to 16 SBS patients in the per protocol investigational group, 10 with end jejunostomy (doses of 0.03 (n = 2), 0.10 (n = 5), or 0.15 (n = 3) mg/kg/day), one with <50% colon in continuity (dose 0.03 mg/kg/day), and five with > or = 50% colon in continuity (dose 0.10 mg/kg/day). Nutrient balance studies, D-xylose tests, and intestinal mucosa biopsies were performed at baseline, on the last three days of treatment, and after three weeks of follow up. Pre-study fasting native GLP-2 levels were determined for the five patients with > or = 50% colon in continuity.ResultsPooled across groups and compared with baseline, teduglutide increased absolute (+743 (477) g/day; p<0.001) and relative (+22 (16)%; p<0.001) wet weight absorption, urine weight (+555 (485) g/day; p<0.001), and urine sodium excretion (+53 (40) mmol/day; p<0.001). Teduglutide decreased faecal wet weight (-711 (734) g/day; p = 0.001) and faecal energy excretion (-808 (1453) kJ/day (-193 (347) kcal/day); p = 0.040). In SBS patients with end jejunostomy, teduglutide significantly increased villus height (+38 (45)%; p = 0.030), crypt depth (+22 (18)%; p = 0.010), and mitotic index (+115 (108)%; p = 0.010). Crypt depth and mitotic index did not change in colonic biopsies from SBS patients with colon in continuity. The most common side effects were enlargement of the stoma nipple and mild lower leg oedema. The improvements in intestinal absorption and decreases in faecal excretion noted after treatment had reversed after the drug free follow up period. A controlled study with a more robust design is ongoing in order to determine the optimal dosage of teduglutide for SBS patients to achieve the maximal effect and utility of this drug in clinical practice.ConclusionTeduglutide, at three dose levels for 21 days, was safe and well tolerated, intestinotrophic, and significantly increased intestinal wet weight absorption in SBS patients with an end jejunostomy or a colon in continuity.

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An updated overview of glucagon-like peptide-2 analog trophic therapy for short bowel syndrome in adults.

Publications

An updated overview of glucagon-like peptide-2 analog trophic therapy for short bowel syndrome in adults.

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