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Targeted therapy of short-bowel syndrome with teduglutide: the new kid on the block

Authors Vipperla K, O'Keefe S

Received 31 August 2014

Accepted for publication 17 November 2014

Published 10 December 2014 Volume 2014:7 Pages 489—495

DOI https://doi.org/10.2147/CEG.S42665

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Andreas M Kaiser


Kishore Vipperla,1 Stephen J O'Keefe2

1Division of General Internal Medicine, University of Pittsburgh Medical Center, 2Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA


Abstract: Extensive intestinal resection impairs the absorptive capacity and results in short-bowel syndrome-associated intestinal failure (SBS-IF), when fluid, electrolyte, acid-base, micro-, and macronutrient homeostasis cannot be maintained on a conventional oral diet. Several factors, including the length and site of the resected intestine, anatomical conformation of the remnant bowel, and the degree of postresection intestinal adaptation determine the disease severity. While mild SBS patients achieve nutritional autonomy with dietary modification (eg, hyperphagia, small frequent meals, and oral rehydration fluids), those with moderate-to-severe disease may develop SBS-IF and become dependent on parenteral support (PS) in the form of intravenous fluids and/or nutrition for sustenance of life. SBS-IF is a chronic debilitating disease associated with a poor quality of life, and carries significant morbidity and health care costs. Medical management of SBS-IF is primarily focused on individually tailored symptomatic treatment strategies, such as antisecretory and antidiarrheal agents to mitigate fluid losses, and PS. However, PS administration is associated with potentially life-threatening complications, such as central venous thromboses, bloodstream infections, and liver disease. In pursuit of a targeted therapy to augment intestinal adaptation, research over the past 2 decades has identified glucagon-like peptide, an intestinotrophic gut peptide that has been shown to enhance intestinal absorptive capacity by causing an increase in the villus length, crypt depth, and mesenteric blood flow and by decreasing gastrointestinal motility and secretions. Teduglutide, a recombinant analog of glucagon-like peptide-2, is the first targeted therapeutic agent to gain approval for use in adult SBS-IF. Teduglutide was shown to result in significant (20%–100%) reduction in PS-volume requirement and have a satisfactory safety profile in three randomized control trials. Further research is warranted to see if reduction in PS dependency translates to improved quality of life and reduced PS-associated complications.


Keywords: short-gut syndrome, intestinal adaptation, glucagon-like peptide-2, teduglutide

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