Teduglutide

After a meal, L-cells in the distal intestine release GLP-2, a hormone that helps maintain the gut lining. Teduglutide binds GLP-2 receptors on hormone-producing cells of the gut lining, on supporting cells just beneath it, and on the gut's own nerve cells. These cells then release local messengers, including IGF-1, nitric oxide and keratinocyte growth factor. GLP-2 signaling also increases blood flow to the intestine and reduces stomach acid secretion. The net effect is thought to be growth of the absorptive lining, with slower stomach emptying and less secretion, which matters in short bowel syndrome, where much of the intestine has been surgically removed. The goal is to absorb more fluid and nutrients so intravenous support can be reduced. The same growth-promoting action underlies the label's warnings about polyps and tumors.

In the 24-week phase 3 STEPS trial, 86 adults with short bowel syndrome and intestinal failure received teduglutide or placebo; 63% on teduglutide versus 30% on placebo reduced their parenteral support volume by more than 20%, and more patients gained at least one day a week free of intravenous support^1,2. Plasma citrulline, a marker of intestinal lining mass, rose on treatment².

In the two-year open-label extension, 88 patients took part; 93% of completers in the longest-treated group met the response definition, and 13 people stopped intravenous support altogether³. In a 24-week phase 3 trial in 59 children, 54% to 69% on two teduglutide regimens reduced parenteral support by at least 20%, versus 11% on standard care⁴. In rodent carcinogenicity studies the drug produced tumors, which is why the label calls for colonoscopy surveillance¹.

FDA-approved in 2012 as Gattex (now Takeda) for adults with short bowel syndrome who depend on parenteral support; the label was later extended to children aged 1 year and older.

Per the FDA label, the most common effects are abdominal pain, nausea, upper respiratory infections, abdominal swelling, injection-site reactions, vomiting, fluid overload and allergic reactions. Warnings cover faster growth of existing tumors and intestinal polyps (colonoscopy is advised after the first year and periodically after), bowel or stoma obstruction, gallbladder, bile duct and pancreatic disease, fluid overload including heart failure, and increased absorption of some oral medicines.

1. FDA label: GattexFDA label (DailyMed)
2. Jeppesen et al., Gastroenterology 2012PubMed
3. Schwartz et al., Clin Transl Gastroenterol 2016PubMed
4. Kocoshis et al., JPEN J Parenter Enteral Nutr 2020PubMed