What Is Tirzepatide?
Quick Answer
Teduglutide (ALX-0600) is a 33-amino acid recombinant analog of human glucagon-like peptide-2 (GLP-2), developed by NPS Pharmaceuticals (acquired by Shire in 2015, subsequently merged into Takeda). The peptide features a single amino acid substitution — Gly2→Ala — that confers resistance to N-termin...
Teduglutide (ALX-0600) is a 33-amino acid recombinant analog of human glucagon-like peptide-2 (GLP-2), developed by NPS Pharmaceuticals (acquired by Shire in 2015, subsequently merged into Takeda). The peptide features a single amino acid substitution — Gly2→Ala — that confers resistance to N-terminal cleavage by dipeptidyl peptidase-4 (DPP-4), extending the plasma half-life from approximately 7 minutes (native GLP-2) to 2–3 hours, enabling once-daily subcutaneous dosing. [1]
Native GLP-2 is a 33-amino acid peptide produced by enteroendocrine L-cells in the ileum and colon, co-secreted with GLP-1 from the proglucagon precursor in response to nutrient ingestion. GLP-2 is the primary endogenous regulator of intestinal adaptation — promoting mucosal growth, enhancing nutrient absorption, reducing intestinal permeability, and modulating intestinal inflammation. [2]
The discovery that GLP-2 drives intestinal mucosal proliferation was made by Daniel J. Drucker, MD at the Lunenfeld-Tanenbaum Research Institute (Mount Sinai Hospital, Toronto) in 1996, establishing the scientific foundation for teduglutide’s development as the first intestinotrophic therapy. [4]
Teduglutide received FDA approval in December 2012 and EMA approval in August 2012 for treatment of adults with short bowel syndrome (SBS) who are dependent on parenteral support (intravenous nutrition and/or fluids). In 2019, FDA approval was expanded to pediatric patients aged ≥1 year. It is marketed as Gattex® (US) and Revestive® (EU and international markets). [3]
In clinical trials, teduglutide demonstrated the ability to reduce parenteral support (PS) volume by ≥20% in significantly more patients than placebo, with some patients achieving complete independence from intravenous nutrition — a clinically transformative outcome for SBS patients who would otherwise require lifelong parenteral support with its associated risks of catheter-related bloodstream infections, liver disease, and reduced quality of life. [5]
References
- Drucker DJ, et al. (1996). Regulation of the biological activity of glucagon-like peptide 2 in vivo by dipeptidyl peptidase IV. Nat Biotechnol, 15(7):673–677.
- Drucker DJ, Yusta B. (2014). Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2. Annu Rev Physiol, 76:561–583.
- FDA. (2012). NDA 203441 Approval Letter — Gattex (teduglutide) for injection. U.S. Food and Drug Administration.
- Drucker DJ, et al. (1996). Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci USA, 93(15):7911–7916.
- Jeppesen PB, et al. (2012). Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology, 143(6):1473–1481.
- Leen JLS, et al. (2011). Mechanism of action of glucagon-like peptide 2 to increase IGF-I mRNA in intestinal subepithelial fibroblasts. Endocrinology, 152(2):436–446.
- Jeppesen PB, et al. (2005). Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients. Gut, 54(9):1224–1231.
- Gattex (teduglutide) Prescribing Information. (2019). Takeda Pharmaceuticals USA, Inc.
- Schwartz LK, et al. (2016). Long-term teduglutide for the treatment of patients with intestinal failure associated with short bowel syndrome. Clin Transl Gastroenterol, 7(2):e142.
- Jeppesen PB, et al. (2018). Factors associated with response to teduglutide in patients with short-bowel syndrome and intestinal failure. Gastroenterology, 154(4):874–885.
- Kocoshis SA, et al. (2020). Safety and efficacy of teduglutide in pediatric patients with short bowel syndrome—intestinal failure. J Pediatr Gastroenterol Nutr, 70(4):521–528.
- Hukkinen M, et al. (2019). Parenteral nutrition-associated cholestasis and its association with teduglutide treatment in neonatal short bowel syndrome. J Pediatr Surg, 54(11):2281–2287.
- Drucker DJ, et al. (1999). Glucagon-like peptide 2 reduces intestinal permeability. Am J Physiol, 276(6):G1420–G1426.
Related Research Questions
Want the complete research review?
View Full Tirzepatide Research Page→FOR RESEARCH USE ONLY
This content is provided for educational and informational purposes only. Products are furnished for in-vitro studies only and are not medicines, drugs, or supplements. Not approved by the FDA to prevent, treat, or cure any condition.