Use of glucagon-like polypeptide 2 analogs for intestinal failure

Abstract

Introduction: Over a half century ago, a component of glucagon was found to have potent gastrointestinal effects. Shortly after proglucagon was sequenced, its component peptides were characterized, and glucagon-like polypeptide-2 (GLP-2) was noted to have the most potent intestinotrophic properties improving fluid and electrolyte balance in experimental animals and humans.

Areas covered: Glucagon-like polypeptide-1 (GLP-1) slows small intestinal motility more effectively, but its intestinotrophic properties are weaker. GLP-2's properties prompted study of its effects upon function of the surgically foreshortened small intestine, but its short half-life limited its usefulness, but the subsequent discovery that substitution of glycine for alanine at the second position of the molecule's N-terminus could lengthen its half-life to 2.5 hours, established efficacy in short bowel management with a single daily subcutaneous injection. Both adult and pediatric studies have shown reduced parenteral nutrition requirements and establishment of enteral autonomy for some patients. More recently, ultralong acting GLP-2 analogs with half-lives of 70-80 hours can improve gastrointestinal function in surgically foreshortened bowel with only one injection every three to seven days.

Expert opinion: Future research is likely to focus upon the potential complementary role of GLP-1 and GLP-2 in treating short bowel syndrome.

Keywords: Short bowel syndrome; apraglutide; glepaglutide; glucagon-like polypeptide-2; intestinal failure; malabsorption; small bowel adaptation; teduglutide.