Use of glucagon-like polypeptide 2 analogs for intestinal failure.

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.