Teduglutide (GLP-2)
Also known as: GLP-2 analog, Gattex, Revestive, Glucagon-like peptide-2
Teduglutide is a GLP-2 (glucagon-like peptide-2) analog that promotes intestinal mucosal growth and function, FDA-approved for short bowel syndrome research and treatment.
Teduglutide (GLP-2) Overview & Molecular Profile
Teduglutide is a recombinant analog of human GLP-2 with a single amino acid substitution (glycine for alanine at position 2) that confers resistance to DPP-4 degradation, extending its half-life from 7 minutes to approximately 2 hours. Unlike GLP-1 which primarily affects glucose metabolism and appetite, GLP-2 specifically targets the gastrointestinal tract to promote intestinal mucosal growth, enhance nutrient absorption, and reduce intestinal inflammation. FDA-approved as Gattex for short bowel syndrome (SBS), teduglutide represents a unique approach to intestinal rehabilitation, potentially reducing dependence on parenteral nutrition in patients with intestinal failure. Research applications include inflammatory bowel disease, chemotherapy-induced mucositis, and intestinal adaptation following surgery.
Mechanism of Action: Receptor Agonism & Metabolic Pathways
Teduglutide activates GLP-2 receptors expressed on intestinal subepithelial myofibroblasts, enteric neurons, and enteroendocrine cells, triggering multiple downstream effects that promote intestinal health. Receptor activation increases crypt cell proliferation and reduces apoptosis, leading to expansion of absorptive surface area through villus growth and crypt hyperplasia. The peptide enhances intestinal blood flow, stimulates release of intestinal growth factors including IGF-1 and EGF, and modulates intestinal permeability. Unlike native GLP-2, the alanine-to-glycine substitution prevents DPP-4 cleavage, allowing sustained receptor activation with once-daily dosing.
Research-Observed Effects
Intestinal Mucosal Growth
Clinical studies demonstrate significant intestinal adaptation with teduglutide treatment, including increased villus height, crypt depth, and overall mucosal surface area measured by histological analysis and citrulline levels. Research in short bowel syndrome patients shows progressive improvement in intestinal absorptive capacity, with benefits typically emerging over 3-6 months of treatment. Studies document enhanced expression of nutrient transporters and digestive enzymes in treated patients. The trophic effects appear most pronounced in remaining small intestine and colon, promoting compensatory adaptation after resection. Animal studies reveal increased intestinal weight, protein content, and DNA synthesis with GLP-2 analog administration.
Parenteral Nutrition Reduction
Clinical trials demonstrate that teduglutide enables significant reduction in parenteral nutrition (PN) requirements in short bowel syndrome patients, with many achieving complete independence from intravenous feeding. The STEPS trial program showed 63% of teduglutide-treated patients reduced PN volume by at least 20% compared to 30% with placebo. Studies document average PN reductions of 4-6 liters weekly, with some patients able to discontinue PN entirely. Research indicates that benefits persist with continued treatment and may be maintained after treatment discontinuation in some patients. These findings have transformed the management of intestinal failure, offering an alternative or complement to surgical bowel-lengthening procedures.
Intestinal Barrier Enhancement
Research demonstrates teduglutide improves intestinal barrier function through multiple mechanisms including enhanced tight junction protein expression, increased mucus production, and reduced intestinal permeability. Studies in animal models of intestinal injury show protection against barrier breakdown and bacterial translocation. Clinical research documents reduced systemic inflammatory markers and decreased infection rates in treated patients. The barrier-enhancing effects may contribute to reduced catheter-related bloodstream infections in PN-dependent patients. These findings have implications for inflammatory bowel disease research and other conditions characterized by intestinal barrier dysfunction.
Inflammatory Bowel Disease Research
Preclinical and early clinical studies explore teduglutide's potential in inflammatory bowel disease, particularly Crohn's disease affecting the small intestine. Animal research demonstrates reduced inflammation, enhanced mucosal healing, and improved histological scores in colitis models. The combination of trophic effects, barrier enhancement, and potential anti-inflammatory properties suggests therapeutic potential for IBD. Clinical trials are investigating teduglutide as adjunctive therapy for refractory Crohn's disease. Research also examines potential applications in ulcerative colitis and radiation-induced intestinal injury.
Research Dosing Information
Clinical studies use 0.05 mg/kg body weight administered once daily by subcutaneous injection. Treatment is typically continued long-term, with efficacy assessments at 6-month intervals. Dose adjustment may be required in patients with renal impairment. Research protocols emphasize gradual weaning of parenteral nutrition as intestinal absorption improves.
Note: Dosing information is provided for research reference only and is based on published studies using research subjects. This is not a recommendation for any use.
Research Studies & References
Teduglutide for the Treatment of Short Bowel Syndrome (STEPS)
Jeppesen PB, Gilroy R, Pertkiewicz M, et al. (2012). Gastroenterology
This pivotal phase 3 trial evaluated teduglutide 0.05 mg/kg daily in 86 patients with short bowel syndrome requiring parenteral nutrition. After 24 weeks, 63% of teduglutide-treated patients achieved at least 20% reduction in parenteral nutrition volume compared to 30% with placebo (p=0.002). The study documented mean PN reductions of 4.4 L/week with teduglutide versus 2.3 L/week with placebo. Secondary endpoints including citrulline levels (marker of intestinal mass) and wet weight absorption showed significant improvements. The results led to FDA approval of Gattex and established teduglutide as the first pharmacologic therapy specifically for intestinal failure rehabilitation.
Long-term safety and efficacy of teduglutide for short bowel syndrome
Schwartz LK, O'Keefe SJ, et al. (2016). Clinical Gastroenterology and Hepatology
This long-term extension study followed patients receiving teduglutide for up to 30 months, evaluating durability of response and long-term safety. Results demonstrated sustained reductions in parenteral nutrition requirements, with progressive improvements in intestinal function over time. The study documented continued benefits in patients who initially responded, with some achieving complete PN independence. Safety analysis confirmed acceptable long-term tolerability, with most adverse events related to underlying short bowel syndrome rather than teduglutide. The findings support long-term teduglutide therapy for intestinal rehabilitation and demonstrate durability of intestinal adaptation induced by GLP-2 receptor activation.
Frequently Asked Questions
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