title: New approaches to the treatments of short bowel syndrome-associated intestinal failure.
abstract: OBJECTIVE
  Teduglutide, a recombinant analog of human glucagon-like peptide 2, has recently been approved in the US and Europe (Gattex and Revestive, respectively) as the first targeted treatment of short bowel syndrome-associated intestinal failure (SBS-IF). Glucagon-like peptide 2 improves structural and functional intestinal adaptation following intestinal resection by decelerating a rapid gastric emptying, by decreasing gastric hypersecretion, by increasing intestinal blood flow and by promoting intestinal growth. This review summarizes the findings from phase 2 and 3 studies preceding the US Food and Drug Administration and the European Medicines Agency approval of subcutaneous teduglutide for this orphan condition.
  
  
  RESULTS
  In a 3-week, phase 2, metabolic balance study, teduglutide increased intestinal wet weight absorption by approximately 700 g/day and reduced fecal energy losses by approximately 0.8 MJ/day (∼200 kcal/day). In two subsequent 24-week, phase 3 studies, teduglutide reduced the need for parenteral support in the same magnitude. Teduglutide had an acceptable tolerability profile, where adverse events generally were of gastrointestinal origin consistent with the known mechanism of action.
  
  
  CONCLUSIONS
  Teduglutide will add incremental benefit to the limited medical treatment armamentarium in SBS patients by maximizing intestinal absorption, decreasing fecal losses, thereby decreasing or even eliminating the need for parenteral support. Future research should target and implement other key hormones with similar and possible additive or synergistic effects, thereby further promoting structural and functional adaptation and intestinal rehabilitation in these severely disabled SBS patients.
authors.affiliation: Department of Medical Gastroenterology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Palle B
authors.initials: PB
authors.lastname: Jeppesen
mesh_terms: D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D053767:Glucagon-Like Peptide 2 / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D010288:Parenteral Nutrition / Q000379:methods; D010455:Peptides / Q000627:therapeutic use*; D012778:Short Bowel Syndrome / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D005765:Gastrointestinal Agents; D053767:Glucagon-Like Peptide 2; D010455:Peptides; C494910:teduglutide