Teduglutide for Short Bowel Syndrome

Teduglutide is a glucagon-like peptide (GLP) analogue recently registered in Australia for the treatment of short bowel syndrome. There are a number of other GLP analogues available including dulaglutide, exenatide, and liraglutide. While these agents are GLP-1 analogues, teduglutide is an analogue of GLP-2.

The glucagon-like peptides, GLP-1 and GLP-2, are naturally secreted in equivalent amounts but can have very different effects in the body. For example, GLP-1 significantly reduces the levels of the lipoprotein chylomicron, while GLP-2 increases its levels. Other effects of GLP-1 include the promotion of glucose-dependent insulin secretion, preservation of pancreatic β-cell function, slowing of gastric emptying, and reduced appetite. These agents have, therefore, been used in the management of obesity and type 2 diabetes. On the other hand, GLP-2 increases intestinal and portal blood flow, inhibits gastric acid secretion, and slows intestinal motility. These effects have led to the use of teduglutide in the treatment of short bowel syndrome in patients who are dependent on parenteral support.

Clinical studies demonstrate that teduglutide promotes normal growth and repair throughout the intestines. Citrulline, an amino acid produced predominantly by enterocytes, can be considered a marker of enterocyte mass. Over a 24-week study, teduglutide increased plasma citrulline by 20.6µmol/L compared to a 0.7µmol/L increase in the placebo group. Patients in the teduglutide group enjoyed a mean reduction in weekly parenteral support of 4.4L compared to 2.3L in the placebo group.

Adverse effects most commonly reported in clinical trials include abdominal pain and distension, nausea, and injection site reactions. Owing to its pharmacological activity, it is thought that teduglutide may be able to produce hyperplastic changes in the small bowel and hepatobiliary tract. Although this has not been demonstrated in clinical studies, patients should be monitored and therapy discontinued in cases of active gastrointestinal malignancy.