Teduglutide

In plain language

Teduglutide is a daily injection sold as Gattex (Revestive in Europe) for people with short bowel syndrome, a condition where surgery or disease has removed so much intestine that they depend on intravenous feeding to survive.

It is a copy of GLP-2, a natural hormone that tells the intestinal lining to grow. With a single amino-acid change, the drug survives long enough in the body to work. It helps the remaining intestine absorb more food and water, letting some patients reduce or stop their intravenous nutrition.

For students

Teduglutide is [Gly2]GLP-2, a 34-residue analogue of human glucagon-like peptide-2 (about 3,752 Da). The glycine-for-alanine substitution at position 2 blocks cleavage by DPP-4, extending the half-life from about 7 minutes (native GLP-2) to roughly 2 hours, enabling once-daily dosing.

GLP-2, characterized by the Drucker and Habener groups in 1996, is an intestinotrophic factor: it increases crypt-cell proliferation, villus height, crypt depth and blood flow in the gut mucosa. In short bowel syndrome, the STEPS trials showed clinically meaningful gains in intestinal absorption (wet weight gain) and reductions in parenteral nutrition volume, establishing enteral autonomy as a realistic goal for a subset of patients. Safety monitoring addresses the theoretical risk of neoplastic proliferation and includes colonoscopy surveillance.

For researchers and instructors

Biochemistry. DPP-4 cleaves the Ala2-Ser3 bond of native GLP-2; the Gly2 substitution is a minimal chemical solution to a protease-liability problem, conceptually parallel to how GLP-1 agonists were stabilized.

Pharmacology. Daily 0.05 mg/kg subcutaneous dosing; trophic effects accumulate over weeks to months; fluid and electrolyte absorption improvements appear earlier than structural adaptation.

Human evidence. STEPS and STEPS-2 randomized trials showed significantly increased intestinal absorption and parenteral nutrition reduction; long-term extension studies support durability and a manageable safety profile.

Teaching point. The definitive example of a trophic peptide hormone turned into a medicine for intestinal failure.