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Intestinal Failure
Published in Praveen S. Goday, Cassandra L. S. Walia, Pediatric Nutrition for Dietitians, 2022
Rashmi Patil, Elizabeth King, Jeffrey Rudolph
GLP-2 is an endogenous gastrointestinal hormone secreted in the distal ileum and colon, inducing small bowel intestinal proliferation. Exogenous administration of the GLP-2 analog, teduglutide, induces intestinal adaptation and is currently the only FDA-approved hormonal therapy that specifically promotes intestinal adaptation. Teduglutide improves water and nutrient absorption by increasing villous height and crypt depth, thus promoting intestinal adaptation. Given the improvement in water and nutrient absorption, the dietitian needs to closely monitor fluid status and growth and adjust the nutrition intervention accordingly.
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Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Following intravenous administration teduglutide plasma clearance was approximately 127 mL/hr/kg which is equivalent to the glomerular filtration rate. Renal elimination was confirmed in a study investigating pharmacokinetics in subjects with renal impairment. No accumulation of teduglutide was observed following repeated subcutaneous administrations.
Management of Acute Intestinal Ischaemia
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Michael J. Stamos, John V. Gahagan
Drugs with trophic effects include glutamine, growth hormone and teduglutide. During the initial stages of SBS, the remaining intestine undergoes adaptation to enhance nutrient absorption. These agents with trophic effects aim to augment this adaptation. Glutamine and growth hormone are the primary energy sources used by the small bowel enterocytes. Glutamine has been shown to increase the length of intestinal villi and improve adaptation in animal models.27 Studies examining the efficacy of glutamine and growth hormone in patients with SBS have been met with mixed results. Therefore, these agents are not used as first-line treatment and are generally reserved for the management of refractory disease. Teduglutide is a glucagon-like peptide 2 (GLP-2) analogue and is the newest medication used in the treatment of SBS. GLP-2 has been shown to stimulate intestinal adaptation and improve nutritional status in patients with SBS.28 In clinical trials, teduglutide demonstrated trophic and absorptive effects on the small intestine, resulting in improved diarrhoea and reduced the need for parenteral nutrition.29 This agent is used in patients with SBS who are dependent on parenteral nutrition and who have failed the more conventional treatments. Although it appears to be well tolerated, some side effects include small bowel or ileostomy obstruction from mucosal hypertrophy, enhanced absorption of other medications and the potential for the development of intestinal polyps. Therefore, it is recommended that a colonoscopy should be performed within six months of initiating the medication and that it should not be used in patients with a known or suspected malignancy within the past five years.
The safety of available treatment options for short bowel syndrome and unmet needs
Published in Expert Opinion on Drug Safety, 2021
Loris Pironi, Emanuel Raschi, Anna Simona Sasdelli
A pooled analysis of four pivotal trials on adults provides the latest advancements on the safety of teduglutide [49]. Data were gathered from two randomized, placebo-controlled phase III studies (CL0600-004 and STEPS) [50,51] and their respective open-label extension studies (CL0600-005 and STEPS-2) [52,53]. Overall, the highest incidence of treatment-emerging AEs (TEAEs) was found in the RCT/extension group exposed to teduglutide, with high discontinuation rate, as expected due to potential reporting and detection biases in the open-label extension studies. Collectively, integrated safety data of 222 person-years of exposure to teduglutide were in line with previous studies: no new safety concerns emerged and the spectrum of TEAEs, mainly gastrointestinal, was consistent with the pharmacodynamics of the drug, the underlying disease state and relevant management. For instance, the intestinotrophic actions of teduglutide may drive stoma enlargement with relevant complications (the most frequently TEAEs in the 173 patients of the extension teduglutide group; 45.6%); the enhancement of intestinal absorptive capacity can lead to fluid overload (reported in 13.3% of patients in the RCT/extension group), which can be a sign of insufficient weaning off IVS and can be managed through adherence to a IVS weaning algorithm. Conversely, improper IVS management can result in signs of dehydration, including headache and decreased weight (more frequently reported >96 weeks) [49].
Proteomic biomarkers in short bowel syndrome : are we ready to use them in clinical activity?
Published in Expert Review of Proteomics, 2021
Noemi Zorzetti, Vito D’Andrea, Augusto Lauro
GLP-2 is a hormone strongly associated with intestinal growth and post-resection IA,[69–73] and many studies have been conducted following the administration subcutaneously of this hormone and/or its synthetic analogue, Teduglutide: the results are encouraging. Intestinal absorption and creatinine clearance improve, achieving the reduction of fecal weight plus the maintenance of fluid and electrolyte’s absorption and diminishing the need of total parenteral nutrition[74–76]. In 2019 FDA approved Teduglutide for 1 year and older children with SBS, after the first approval in 2012 for adults[77]. Also in pediatric SBS, the role of Teduglutide is safe and effective with significant reduction of parenteral support and advancements in enteral nutrition re- feeding[78–80].
Advances in non-surgical treatment for pediatric patients with short bowel syndrome
Published in Expert Opinion on Orphan Drugs, 2020
Danielle Wendel, Beatrice E. Ho, Tanyaporn Kaenkumchorn, Simon P. Horslen
The most promising recent advances in treatment have been related to the GLP-2 analogue, teduglutide (Takeda). Teduglutide is the only hormone analogue approved for use in the US and Europe for pediatric patients ≥1 year of age with PN dependent SBS. GLP-2 is an enteroendocrine hormone that is produced by the L-cells in the terminal ileum and proximal colon as a result of luminal nutrients getting to the distal bowel [116]. Increased amounts are produced when the small bowel and colon are in continuity and with exposure to long-chain fatty acids [117,118]. In animal models GLP-2 has been shown to promote small intestinal adaptation [14]. Teduglutide was developed as an analogue of GLP-2 with a longer half-life that could be dosed subcutaneously on a daily basis. In human trials teduglutide has been shown to decrease gastric emptying, increase villus height and crypt depth leading to improvements in fluid absorption and reductions in PN support although the beneficial effects appear to reverse with cessation of the drug [119,120]. In addition to the adult studies, two multicenter studies in pediatrics were completed showing a reduction in parenteral support, and in some cases cessation of PN, in children with SBS treated with teduglutide [121,122]. FDA approval was given for adult use of teduglutide for SBS in 2012 and more recently in 2019 for children over 1 year of age.