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Comparing the Intestinotrophic Effects of 2 Glucagon-Like Peptide-2 Analogues in the Treatment of Short-Bowel Syndrome in Neonatal Piglets.

Authors
  • Pauline, Mirielle L1
  • Nation, Patrick N2
  • Wizzard, Pamela R1
  • Hinchliffe, Tierah1
  • Wu, Tong1, 3
  • Dimitriadou, Violetta4
  • Turner, Justine M1
  • Wales, Paul W5
  • 1 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. , (Canada)
  • 2 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada. , (Canada)
  • 3 Shanghai Medical College, Fudan University, Shanghai, China. , (China)
  • 4 VectivBio, Montreal, Quebec, Canada. , (Canada)
  • 5 Department of Surgery, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada. , (Canada)
Type
Published Article
Journal
JPEN. Journal of parenteral and enteral nutrition
Publication Date
Mar 01, 2021
Volume
45
Issue
3
Pages
538–545
Identifiers
DOI: 10.1002/jpen.1853
PMID: 32437048
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

In treating short-bowel syndrome (SBS), autonomy from parenteral nutrition (PN) relies upon intestinal adaptation, which can be augmented by glucagon-like peptide-2 (GLP-2) analogues. In neonatal piglets with SBS, we compared intestinal adaptation following treatment with 2 GLP-2 analogues: teduglutide (TED) and apraglutide (APRA) METHODS: Following 75% distal small-intestinal resection, piglets were allocated to 4 treatment groups: saline (CON: n = 8), twice weekly APRA (5 mg/kg/dose; n = 8), and TED once daily (TED, 0.05 mg/kg/dose; n = 8) or twice daily (TEDBID, 0.05 mg/kg/dose; n = 7). Pharmacokinetic (PK) studies were undertaken, and on day 7, small-intestinal length and weight were measured and jejunal tissue collected for histology. PK profiles were different between the 2 analogues. To achieve a comparable exposure to APRA, TED requires twice daily injection (TEDBID). Compared with CON, APRA and TEDBID increased small-bowel length (cm) (CON: 141, APRA: 166, TED: 153, TEDBID: 165; P = .004), whereas APRA increased small-bowel weight (g) (CON: 26, APRA: 33, TED: 28, TEDBID: 31; P = .007) and villus height (mm) (CON: 0.59, APRA: 0.90, TED: 0.58, TEDBID: 0.74; P < .001). APRA injected only twice during the 7 consecutive days demonstrated a superior intestinotrophic effect compared with TED injected once daily. Even at more comparable drug exposure, when TED was injected twice a day, APRA showed superior trophic activity at the mucosal level. This is highly relevant for the treatment of pediatric SBS, given the markedly lower dose frequency by subcutaneous injection of APRA. © 2020 American Society for Parenteral and Enteral Nutrition.

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