Teduglutide

Teduglutide (Gattex/Revestive) — GLP-2 Analog

Evidence & Status

  • FDA Approved
  • Strong Human Evidence
  • Strong

At a Glance

An FDA-approved GLP-2 analog for adults and pediatric patients 1 year of age and older with short bowel syndrome who are dependent on parenteral support. It promotes intestinal adaptation and absorption and can reduce parenteral-support requirements.

Plain English

Researchers study Teduglutide because it activates the GLP-2 pathway, which promotes growth and repair of the intestinal lining. It was developed for short bowel syndrome, a serious condition where a significant portion of the small intestine is absent or non-functional and patients may depend on intravenous nutrition. By helping the remaining intestine absorb more, Teduglutide can reduce the amount of parenteral support some patients need. Some patients may achieve independence from parenteral support, but that is not the expected outcome for everyone. It also demonstrates that intestinal growth can be pharmacologically influenced, an important concept for gut biology research.

Overview

Teduglutide is a DPP-4-resistant analog of native GLP-2 (glucagon-like peptide-2), differing from the endogenous 33-amino-acid peptide by a glycine substitution at position 2. GLP-2 is an intestinotrophic hormone that promotes intestinal adaptation and absorption. In short bowel syndrome (SBS), where extensive bowel resection can leave patients dependent on parenteral support, teduglutide promotes adaptation of the remaining intestine and can reduce parenteral-support requirements. Some patients may achieve independence from parenteral support, but this is not the expected outcome for every patient. Understanding teduglutide benefits from the companion native GLP-2 entry in this database, which explains the endogenous pathway.

Research Summary

In the pivotal 24-week randomized study in patients with short bowel syndrome and intestinal failure, 43 patients received teduglutide 0.05 mg/kg/day and 43 received placebo. The primary responder definition was a reduction of at least 20% in weekly parenteral-support volume from baseline at weeks 20 and 24. Responders included 27 of 43 patients (63%) receiving teduglutide and 13 of 43 patients (30%) receiving placebo (P = .002). At week 24, mean reduction in parenteral-support volume was 4.4 ± 3.8 L/week with teduglutide and 2.3 ± 2.7 L/week with placebo. Teduglutide is an established treatment for reducing parenteral-support requirements in SBS patients who are dependent on parenteral support.

Research Areas

  • Short bowel syndrome
  • Intestinal adaptation
  • Parenteral nutrition weaning
  • GLP-2 receptor pharmacology
  • Gut trophic factors

Safety & Risks

Serious Risks

  • Acceleration of neoplastic growth and gastrointestinal polyps — GATTEX has the potential to cause hyperplastic changes including neoplasia. In adults, colonoscopy and upper GI endoscopy with removal of polyps are performed within 6 months before treatment, at 1 year, then every 5 years or more often as needed; pediatric patients receive fecal occult blood testing before treatment and annually, colonoscopy/sigmoidoscopy is recommended after 1 year of treatment and every 5 years thereafter while on continuous treatment, and new or unexplained blood in stool requires colonoscopy/sigmoidoscopy and upper GI endoscopy.
  • Intestinal or stomal obstruction has been reported; temporarily discontinue GATTEX while obstruction is clinically managed.
  • Biliary and pancreatic disease — cholecystitis, cholangitis, cholelithiasis, and pancreatitis have been reported; bilirubin, alkaline phosphatase, lipase, and amylase monitoring is recommended before treatment and at least every 6 months during treatment.
  • Fluid overload and congestive heart failure can occur due to enhanced fluid absorption; adjust parenteral support and reassess treatment, especially in patients with underlying cardiovascular disease.
  • Increased absorption of concomitant oral medications can increase exposure; monitor drugs requiring titration or with a narrow therapeutic index for adverse reactions, and a dose reduction may be required.

Reported Side Effects

  • Abdominal pain
  • Nausea
  • Upper respiratory tract infection
  • Abdominal distension
  • Injection site reaction
  • Vomiting
  • Fluid overload
  • Hypersensitivity
United States
GATTEX is indicated for treatment of adults and pediatric patients 1 year of age and older with Short Bowel Syndrome (SBS) who are dependent on parenteral support.
United Kingdom
EMA-approved (Revestive) for SBS in adults
Australia
TGA-approved for SBS
Canada
Health Canada-approved for SBS

Citations & Sources