Teduglutide enhances structural adaptation of the small intestinal mucosa in
patients with short bowel syndrome.
Author(s): Tappenden KA(1), Edelman J, Joelsson B.
Affiliation(s): Author information:
(1)Department of Nutrition and Gastrointestinal Physiology, University of Illinois
at Urbana-Champaign, Champaign, IL 61820, USA. tappende@uiuc.ed
Publication date & source: 2013, J Clin Gastroenterol. , 47(7):602-7
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.
AIMS: 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.
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