title: Teduglutide enhances structural adaptation of the small intestinal mucosa in patients with short bowel syndrome.
abstract: BACKGROUND
  Intestinotrophic therapies, such as glucagon-like peptide-2 (GLP-2) analogs, may enhance intestinal adaptation and reduce dependence on parenteral nutrition (PN) in patients with intestinal failure associated with short bowel syndrome (SBS-IF). However, because GLP-2 enhances cellular growth, there is concern that GLP-2 analogs may also encourage growth of malignant cells.
  
  
  OBJECTIVE
  To histologically examine the effects of teduglutide, a recombinant human GLP-2 analog, on the mucosa of the small and large intestine for indications of dysplastic transformation.
  
  
  METHODS
  In a multicenter, prospective, randomized, placebo-controlled study, 83 PN-dependent patients with SBS-IF were monitored for several weeks to ensure optimal and stable PN. Patients were then randomized to receive 24 weeks of placebo (n=16), teduglutide (0.5 mg/kg/d; n=35), or teduglutide (0.10 mg/kg/d; n=32).
  
  
  RESULTS
  Biopsies were obtained from 77 patients to yield 390 individual histologic interpretations. After 6 months of treatment, no features of dysplasia were found in any biopsy from the large or small intestine of patients receiving placebo or either dose of teduglutide. New secondary diagnoses, such as eosinophilic colitis or Crohn's disease, were found at a low frequency overall: teduglutide (0.05 mg/kg/d; range, 3.1% to 6.3%); teduglutide (0.10 mg/kg/d, 3.3%); placebo (range, 6.7% to 13.3%).
  
  
  CONCLUSIONS
  Although this histologic substudy of biopsy samples was not powered to detect differences in occurrence of dysplasia between teduglutide-treated patients and those randomized to placebo, it demonstrated that no dysplasia or other pathologic processes were evident within the intestinal mucosa in the placebo group or the 2 teduglutide groups after 6 months of treatment.
authors: Department of Nutrition and Gastrointestinal Physiology, University of Illinois at Urbana-Champaign, Champaign, IL 61820, USA. tappende@uiuc.ed
authors: Kelly A
authors: KA
authors: Tappenden
authors: Jeffrey
authors: J
authors: Edelman
authors: Bo
authors: B
authors: Joelsson
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D001706:Biopsy; D015331:Cohort Studies; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology*; D007420:Intestine, Large / Q000502:physiology; D007421:Intestine, Small / Q000502:physiology*; D010288:Parenteral Nutrition; D010455:Peptides / Q000627:therapeutic use*; D011446:Prospective Studies; D012778:Short Bowel Syndrome / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D005765:Gastrointestinal Agents; D010455:Peptides; C494910:teduglutide