Short bowel syndrome: the role of GLP-2 on improving outcome

Abstract

The medical management of short bowel syndrome frequently requires lifelong parenteral nutrition. Methods of increasing intestinal absorption and reducing parenteral nutrition dependence, by improving postresection intestinal adaptation, are increasingly being explored. Glucagon-like peptide-2 (GLP-2) is an important intestinotrophic growth factor and mediator of intestinal adaptation. This review summarizes our current understanding of GLP-2 physiology and provides an update on clinical trials in short bowel syndrome and related conditions. There is growing understanding how the effects of GLP-2 are mediated by downstream effectors such as insulin-like growth factor-1. In the treatment of short bowel syndrome, GLP-2 and the long-acting GLP-2 analogue teduglutide (Gattex) are effective in improving fluid absorption. A recent multicentre, placebo-controlled study demonstrates that this can translate into meaningful reductions in parenteral nutrition requirements. Treatment dose and timing of treatment initiation might influence the mucosal growth response. Most of the small intestine has to be preserved to facilitate the previously documented benefits of GLP-2 on bone metabolism. Therapeutic uses of GLP-2 in other gastrointestinal conditions are being explored. GLP-2 treatment appears well tolerated, although concerns about the long-term use of this growth-promoting agent remain. GLP-2 therapy holds promise as an adjuvant treatment modality for short bowel syndrome and other gastrointestinal disorders.