Chemical Identity

Property	Value
Chemical Formula	C164H252N44O55
Molecular Weight	3752 Da
CAS Number	197922-42-2
Peptide Class	GLP-2 Analog (33 amino acids)
Modification	Gly2 substitution (DPP-4 resistant)
Route	SC injection

Structure

Teduglutide (Gattex) is a recombinant analog of human GLP-2 with a single amino acid substitution: glycine replaces alanine at position 2. This modification confers resistance to DPP-4 cleavage, extending the half-life from 7 minutes (native GLP-2) to approximately 2 hours.

Mechanism of Action

Like native GLP-2, teduglutide activates GLP-2 receptors on intestinal subepithelial myofibroblasts, stimulating mucosal growth, enhancing villus height and crypt depth, improving barrier function, and increasing mesenteric blood flow. The extended half-life provides sustained intestinal trophic effects.

Clinical Applications

• Short bowel syndrome: Adults dependent on parenteral nutrition (Gattex)
• Intestinal failure: Reducing PN volume and frequency
• STEP trials: 63% achieved 20-50% PN volume reduction
• Pediatric SBS: Under investigation

Pharmacokinetics

• Half-life: 2 hours (vs 7 min for native GLP-2)
• Tmax: 3-5 hours (SC)
• Bioavailability: 88% (SC)
• Metabolism: Proteolytic degradation
• Dosing: 0.05 mg/kg SC once daily

Safety and Side Effects

Abdominal pain (30%), nausea (22%), injection site reactions (13%), headache, and upper respiratory infections. Intestinal polyp monitoring recommended (colonoscopy at baseline and 1 year). Theoretical risk of colorectal neoplasia.

References

• Jeppesen, P.B., et al. (2011). Teduglutide for short bowel syndrome. New England Journal of Medicine, 365, 1789-1799.
• O’Keefe, S.J., et al. (2013). Safety and efficacy of teduglutide. Alimentary Pharmacology & Therapeutics, 37, 260-272.