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Pernille Wismann, Søren L Pedersen, Gitte Hansen, Karin Mannerstedt, Philip J Pedersen, Palle B Jeppesen, Niels Vrang, Keld Fosgerau, Jacob Jelsing
AIM: Analogues of several gastrointestinal peptide hormones have been developed into effective medicines for treatment of diseases such as type 2 diabetes mellitus (T2DM), obesity and short bowel syndrome (SBS). In this study, we aimed to explore whether the combination of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) into a potent co-agonist could provide additional benefits compared to existing monotherapies. METHODS: A short-acting (GUB09-123) and a half-life extended (GUB09-145) GLP-1/GLP-2 co-agonist were generated using solid-phase peptide synthesis and tested for effects on food intake, body weight, glucose homeostasis, and gut proliferation in lean mice and in diabetic db/db mice...
March 11, 2018: Physiology & Behavior
Pengyu Yang, Huafei Zou, Candy Lee, Avinash Muppidi, Elizabeth Chao, Qiangwei Fu, Xiaozhou Luo, Danling Wang, Peter G Schultz, Weijun Shen
Glucagon-like peptide 2 (GLP-2) is a hormone that has been shown to stimulate intestinal growth and attenuate intes-tinal inflammation. Despite being efficacious in a variety of animal models of disease, its therapeutic potential is ham-pered by the short half-life in vivo. We now describe a highly potent, stapled long-acting GLP-2 analog, Peptide 10, that has a more than 10-fold longer half-life than teduglutide and improved intestinotrophic and anti-inflammatory effects in mouse models of DSS-induced colitis...
March 12, 2018: Journal of Medicinal Chemistry
Kwai Lam, Lauren Schwartz, Jennifer Batisti, Kishore R Iyer
BACKGROUND: Teduglutide is a glucagon-like peptide 2 (GLP-2) analog that has been approved for the treatment of adult short bowel syndrome (SBS)-associated intestinal failure (IF; SBS-IF). Teduglutide increases villus height and crypt depth in the small bowel mucosa, promoting nutrition absorption and enteral independence from parenteral nutrition (PN). We aim to report our single-center experience with teduglutide in adult patients with SBS to provide real-world context to its use. METHOD: We conducted a retrospective analysis on patients managed within our tertiary-level intestinal rehabilitation program to identify patients with SBS-IF treated with teduglutide from 2009-2015...
January 2018: JPEN. Journal of Parenteral and Enteral Nutrition
Palle Bekker Jeppesen, Simon M Gabe, Douglas L Seidner, Hak-Myung Lee, Clément Olivier
BACKGROUND & AIMS: Clinical studies showed teduglutide to increase urine production and reduce need for parenteral support volume in patients with short bowel syndrome (SBS) with intestinal failure, increasing intestinal wet weight absorption and reducing diarrhea. However, the effects of teduglutide on parenteral support vary among patients. We performed a post hoc analysis of a phase III placebo-controlled study to identify characteristics of patients in whom teduglutide has the largest effects on parenteral support volume response...
November 22, 2017: Gastroenterology
Jarmila Křížová, Pavel Trachta, Eva Kotrlíková
Gut resection is followed by wide changes in the gastrointestinal tract. The goal is to increase nutrient, water and mineral absorption in the remnant intestine. These changes are going on for several months. They affect gut mucosa structure, intestine peristaltic activity and enterocytes function. The crucial role is ileum preserving. Ileum has higher adaptation ability comparing to jejunum and inhibits peristaltic function of proximal parts of GIT. A lot of factors involved in intestinal adaptation were identified, hormones, growth factors, regulating peptides, intracellular signalizing cascades, cytokines and tissue factors...
2017: Vnitr̆ní Lékar̆ství
Mohammad M Jami, Russell J Merritt
No abstract text is available yet for this article.
December 2017: Digestive Diseases and Sciences
Beatriz Pinto da Costa, Ana Cristina Gonçalves, Ana Margarida Abrantes, Paulo Matafome, Raquel Seiça, Ana Bela Sarmento-Ribeiro, Maria Filomena Botelho, Francisco Castro-Sousa
Purpose: To investigate the inflammatory and redox responses to teduglutide on an animal model of laparotomy and intestinal anastomosis. Methods: Wistar rats (n=62) were allocated into four groups: "Ileal Resection and Anastomosis" vs. "Laparotomy", each one split into "Postoperative Teduglutide Administration" vs. "No Treatment"; and euthanized at the third or the seventh day. Ileal and blood samples were recovered at the baseline and at the euthanasia. Flow cytometry was used to study the inflammatory response (IL-1α, MCP-1, TNF-α, IFN-γ and IL-4 levels), oxidative stress (cytosolic peroxides, mitochondrial reactive species, intracellular glutathione and mitochondrial membrane potential) and cellular viability and death (annexin V/propidium iodide double staining)...
August 2017: Acta Cirúrgica Brasileira
Beatriz P Costa, Ana C Gonçalves, Ana M Abrantes, Paulo Matafome, Raquel Seiça, Ana B Sarmento-Ribeiro, Maria Filomena Botelho, Francisco Castro-Sousa
BACKGROUND: Teduglutide is an enterotrophic analog of glucagon-like peptide 2 approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the effects of teduglutide administration on the gene regulation of fibrogenesis during the intestinal anastomotic healing on an animal model. METHODS: Wistar rats (n = 62) were assigned into four groups: "Ileal Resection and Anastomosis" or "Laparotomy," each one subdivided into "Postoperative Teduglutide Administration" or "No Treatment," and sacrificed at the third or at the seventh days, with ileal sample harvesting...
August 2017: Journal of Surgical Research
Andrew Ukleja, Baker Alkhairi, Pablo Bejarano, Amareshwar Podugu
Teduglutide (TG) is approved for the treatment of parenteral nutrition (PN)-dependent adult patients with short bowel syndrome (SBS). Its well-known adverse effect is expedited growth of colon polyps and potential formation of new polyps. Apart from animal studies, de novo development of duodenal polyps in a patient during TG therapy has not been reported in the literature. We report a case of a 71-year-old man with SBS on TG who developed multiple new duodenal polyps that were found incidentally during a diagnostic endoscopy...
June 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
Ferenc Sipos, Györgyi Műzes
Malabsorption is a major and common clinical characteristics of short bowel syndrome (SBS) and inflammatory bowel diseases (IBD). Traditional treatment opportunities have focused on decreasing malabsorptive losses via dietary modifications and antisecretory/antidiarrheal agents. However, novel therapeutic modalities aim to enhance the absorptive capacity of the residual bowel by the administration of different intestinal growth factors including teduglutide. In a current study the existence of two distinct functional putative epithelial stem cell subpopulations (i...
June 7, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
Stanisław Klek, Marek Kunecki, Jacek Sobocki, Konrad Matysiak, Katarzyna Karwowska, Krystyna Urbanowicz
OBJECTIVE: Teduglutide is an active, glucagon-like peptide (GLP)-2 analog with proven clinical efficacy regarding intestinal adaptation in patients with short bowel syndrome (SBS). There are two factors that preclude its reimbursement, and thereby, its availability: its cost (reaching ∼$300,000/y)-which significantly exceeds the cost of home parenteral nutrition (HPN) in most countries-and the lack of clear guidelines. The aim of this study was to create evidence-based working criteria for the use of teduglutide that could be used in clinical settings...
June 2017: Nutrition
Jintao Gu, Shuo Liu, Nan Mu, Tonglie Huang, Wangqian Zhang, Huadong Zhao, Zhen Shu, Cun Zhang, Qiang Hao, Weina Li, Xiaochang Xue, Wei Zhang, Yingqi Zhang
Although radiotherapy is a highly effective treatment for abdominal or pelvic cancer patients, it can increase the incidence of severe gastrointestinal (GI) toxicity. As an intestinal growth factor, glucagon-like peptide 2 (GLP-2) has been shown to improve the preclinical models of both short bowel syndrome and inflammatory bowel disease by stimulating intestinal growth. Teduglutide ([Gly(2)]GLP-2), a recombinant human GLP-2 variant, has a prolonged half-life and stability as compared to the native GLP-2 peptide, but still requires daily application in the clinic...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Beatriz P Costa, Ana C Gonçalves, Ana M Abrantes, Raquel Alves, Paulo Matafome, Raquel Seiça, Ana B Sarmento-Ribeiro, M Filomena Botelho, Francisco Castro-Sousa
BACKGROUND: Previous studies suggest that intestinal epithelial stem cells (IESC), critical drivers of homeostasis and regeneration, include two subpopulations: crypt-based columnar and "position +4" stem cells, identified by Lgr5 and Bmi1 biomarkers, respectively. Teduglutide is an enterotrophic counterpart of glucagon-like peptide 2. This study aimed to investigate the response of putative IESC to surgical injury and teduglutide administration on an animal model of intestinal resection and anastomosis...
March 31, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
Lore Billiauws, Julie Bataille, Vanessa Boehm, Olivier Corcos, Francisca Joly
The European Society for Clinical Nutrition has published recommendations on the 'definition and classification of intestinal failure (IF)'. Two criteria must be present: a 'decreased absorption of macronutrients and/or water and electrolytes due to a loss of gut function' and the 'need for parenteral support'. Home parenteral support (HPS) is the primary treatment for chronic IF but is associated with complications. Areas covered: The principal cause of chronic IF is short bowel syndrome (SBS). The aim of treatment is to maximize intestinal absorption and reduce or eliminate the need for HPS to achieve the best possible quality of life...
May 2017: Expert Opinion on Biological Therapy
Siddhartha Oke, Merlin N M Walter, Tahera Ansari, Simon M Gabe
PURPOSE OF REVIEW: To examine the most recent literature on the clinical trials associated with the relevant growth factors that have been of interest in the treatment of short bowel. RECENT FINDINGS: Short bowel is a rare but devastating condition that condemns patients to lifelong parenteral support. Historically, treatment options negating the need for parenteral support were limited. Therapeutic growth factor use is of interest, but the clinical trial data are inconclusive...
May 2017: Current Opinion in Gastroenterology
Esther S Kim, Susan J Keam
Subcutaneous teduglutide (Revestive® ), a glucagon-like peptide-2 analogue that increases intestinal absorption, is approved in the EU for the treatment of short bowel syndrome (SBS) in patients aged ≥1 year who are stable following a period of postsurgical intestinal adaptation. In a phase III trial in adults with SBS intestinal failure (IF) dependent on parenteral support (PS), a significantly greater proportion of teduglutide 0.05 mg/kg/day than placebo recipients achieved a ≥20% reduction in weekly PS volume from baseline to week 20 and maintained it to week 24...
March 2017: Drugs
K Chen, J Xie, C Tang, J Zhao, C Olivier, P B Jeppesen, J Signorovitch
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Kishore R Iyer, Marek Kunecki, Joseph I Boullata, Ken Fujioka, Francisca Joly, Simon Gabe, Ulrich-Frank Pape, Stéphane M Schneider, María Nuria Virgili Casas, Thomas R Ziegler, Benjamin Li, Nader N Youssef, Palle B Jeppesen
BACKGROUND: In phase III clinical studies, treatment with teduglutide was associated with clinically meaningful reductions (≥20% from baseline) in parenteral support (PS; parenteral nutrition and/or intravenous fluids) requirements in adult patients with intestinal failure associated with short bowel syndrome (SBS-IF). This analysis reports clinical characteristics of patients who achieved complete independence from PS during teduglutide treatment. MATERIALS AND METHODS: Post hoc analysis of adult patients who achieved complete PS independence during treatment with teduglutide 0...
August 2017: JPEN. Journal of Parenteral and Enteral Nutrition
Beth A Carter, Valeria C Cohran, Conrad R Cole, Mark R Corkins, Reed A Dimmitt, Christopher Duggan, Susan Hill, Simon Horslen, Joel D Lim, David F Mercer, Russell J Merritt, Peter F Nichol, Luther Sigurdsson, Daniel H Teitelbaum, John Thompson, Charles Vanderpool, Juliana F Vaughan, Benjamin Li, Nader N Youssef, Robert S Venick, Samuel A Kocoshis
OBJECTIVE: To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF). STUDY DESIGN: This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0...
February 2017: Journal of Pediatrics
Ken Fujioka, Khursheed Jeejeebhoy, Ulrich-Frank Pape, Benjamin Li, Nader N Youssef, Stéphane M Schneider
BACKGROUND: Narcotic agents are frequently administered to manage increased intestinal motility in patients with short bowel syndrome, but long-term use is associated with gastrointestinal (GI) complaints. This analysis evaluated the incidence of narcotic use and abdominal adverse events among patients with short bowel syndrome receiving teduglutide. MATERIALS AND METHODS: Pooled data from patients who received ≥1 dose of teduglutide 0.05 mg/kg/d (n = 77) or placebo (n = 59) in either of 2 randomized, double-blind, phase III studies were analyzed...
August 9, 2016: JPEN. Journal of Parenteral and Enteral Nutrition
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