Glucagon-like peptide-2 analogues for Crohn’s disease patients with short bowel syndrome and intestinal failure

Abstract

Short bowel syndrome (SBS) with intestinal failure (IF) is a rare but severe complication of Crohn’s disease (CD), which is the most frequent benign condition that leads to SBS after repeated surgical resections, even in the era of biologics and small molecules. Glucagon-like peptide-2 analogues have been deeply studied recently for the treatment of SBS-IF. These drugs have a significant intestinotrophic effect and the potential to reduce the chronic dependence of SBS-IF patients on parenteral support or nutrition. Teduglutide has been approved for the treatment of SBS-IF, and apraglutide is currently in clinical development. The use of these drugs was examined with a focus on their use in CD patients.

Intestinal Enteroendocrine Cells: Present and Future Druggable Targets

“…Likewise, an anti-inflammatory role of GLP-1 and GLP-1 agonists has been reported in humans and mice [69,70]. Clinical trials are underway for the use of GLP-2 analogs (teduglutide and apraglutide) for the treatment of CD and short bowel syndrome [71,72], with promising results thus far. Teduglutide has been approved and is currently in use.…”

Endoscopic Management of Strictures in Crohn’s Disease: An Unsolved Case

“…Antibodies targeting proteins involved in collagen remodeling have been identified as a possible therapeutic strategy as well; the inhibition of matrix metalloproteinase-9 (MMP-9), a type IV collagenase overexpressed in fistulizing and structuring CD, led to reduced collagen deposition in heterotopic xenograft models of intestinal fibrosis [75]. Among other unexplored therapeutic targets is teduglutide, already approved for the treatment of short bowel syndrome, showing a reduction of fibrogenesis and improved fibrolysis since the first week after surgery in a murine model of ileal resection and anastomosis [76,77]. More recently, the antifibrogenic effects of glucagon-like peptide 2 (GLP2) have been demonstrated even in the liver of a murine model of cholangitis [78].…”