Teduglutide

Gattex / Revestive

Teduglutide is a recombinant analog of glucagon-like peptide-2 (GLP-2), a 33-amino-acid intestinotrophic hormone secreted by enteroendocrine L-cells of the distal gut. Native GLP-2 is rapidly inactivated by the enzyme DPP-4; teduglutide carries a single amino-acid substitution (alanine-to-glycine at position 2) that confers resistance to DPP-4 cleavage, extending its half-life from minutes to a clinically useful range and allowing once-daily subcutaneous dosing. Unlike GLP-1 analogs, which target metabolism and appetite, GLP-2 is a growth factor for the intestinal epithelium. Teduglutide stimulates proliferation of the crypt cells, increases villus height and mucosal surface area, improves intestinal blood flow, reduces gastric emptying and secretion, and enhances the barrier function of the gut lining. The net effect is greater absorptive capacity of the remaining bowel. Teduglutide is approved (as Gattex in the US and Revestive in the EU) for the treatment of short bowel syndrome (SBS) in patients who are dependent on parenteral (intravenous) nutrition and fluids. In this population, remaining intestine cannot absorb enough nutrients and water, and teduglutide's mucosal-growth effect can reduce or, in some cases, eliminate the need for parenteral support. It is one of the few peptides in this reference that carries full regulatory approval and an established clinical evidence base. Because it stimulates intestinal cell growth, teduglutide requires colonoscopic surveillance for polyps and carries theoretical concerns about promoting neoplasia, which shape its labeling and monitoring requirements.