Durability of Linear Small-Intestinal Growth Following Treatment Discontinuation of Long-Acting Glucagon-Like Peptide 2 (GLP-2) Analogues.

Abstract

BACKGROUND:

Short-bowel syndrome is the leading cause of pediatric intestinal failure, resulting in dependency on long-term parenteral nutrition (PN). To promote enteral autonomy in neonates, a key outcome may be intestinal growth in length. The purpose of this study was to determine if intestinal lengthening persists following discontinuation of treatment with 1 of 2 GLP-2 analogues with different pharmacokinetic profiles.

METHODS:

Neonatal short-bowel piglets were assigned to saline control (S), 7-day treatment with teduglutide (T) (0.05 mg/kg twice daily), or 7-day treatment with apraglutide (A) (5 mg/kg twice weekly). Comparisons were made between day 7 and day 14 endpoints using analysis of variance. Data included small-intestine length, weight, histology, and quantitative polymerase chain reaction analysis of mucosal transcripts for peptide growth factors and their receptors, nutrient transporters, and tight-junction proteins.

RESULTS:

Compared with control, 7 days of GLP-2 analogue treatment induced mucosal adaptation based on villus hyperplasia (P = .003), which was not durable 7 days after treatment cessation (day 14; P = .081). Treatment increased intestinal growth in length by day 7 (P = .005), which was maintained (by T) or further increased (by A) at day 14 (P < .001). No significant differences in mucosal transcripts were detected.

CONCLUSION:

Unlike mucosal adaptation, intestinal growth appears to be a lasting outcome of treatment with long-acting GLP-2 analogues in a neonatal piglet short-bowel model. This has significant clinical implications for neonates, given their potential for intestinal growth. Intestinal lengthening varies between analogues with different half-lives; however, molecular mechanisms require further elucidation.

• Authors: Tierah Hinchliffe, Mirielle L Pauline, Pamela R Wizzard, Patrick N Nation, Patricia Brubaker, Jhenielle R Campbell, Yunji Kim, Violetta Dimitriadou, Paul W Wales, Justine M Turner
• Journal: JPEN. Journal of parenteral and enteral nutrition (JPEN J Parenter Enteral Nutr) Vol. 45 Issue 7 Pg. 1466-1474 (09 2021) ISSN: 1941-2444 [Electronic] United States
• PMID: 33241564 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 American Society for Parenteral and Enteral Nutrition.

Chemical References

• Glucagon-Like Peptide 2
• Peptides
• apraglutide

Topics

• Adaptation, Physiological
• Animals
• Disease Models, Animal
• Glucagon-Like Peptide 2
• Humans
• Peptides
• Short Bowel Syndrome (drug therapy)
• Swine