Teduglutide: Gattex/Revestive gut-repair drug for short bowel syndrome
FDA-approved prescription drug that helps people who have lost most of their small intestine absorb enough nutrients to reduce or eliminate their need for intravenous feeding.
- Class
- GLP-2 receptor agonist (DPP-4-resistant analog of glucagon-like peptide-2)
- Status
- FDA-approved prescription drug as Gattex (adult short bowel syndrome, December 2012; pediatric indication added 2019); also approved in the EU, UK, Canada, and Australia as Revestive
- Best-supported effect
- Reduction of parenteral support (PN volume and infusion days) in adults and children with short bowel syndrome dependent on parenteral nutrition, supported by the STEPS, STEPS-2, and STEPS-3 pivotal trials
- Main caveat
- Benefit is treatment-dependent — intestinotrophic effect requires ongoing daily injections, and PN dependence regresses if therapy stops. Long-term colorectal neoplasia risk from chronic intestinotrophic stimulation is still being surveilled, and the drug is not a general "gut health" or leaky-gut treatment.
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A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
Teduglutide (sold as Gattex in the US and Revestive in the EU, UK, Canada, and Australia) is a prescription drug that helps people who have lost most of their small intestine absorb enough nutrients and fluid to reduce — or in some cases eliminate — their dependence on intravenous nutrition. It does this by stimulating the remaining intestinal lining to grow and become more efficient. The FDA approved it for adult short bowel syndrome in December 2012 and extended that approval to children in 2019, making it the first disease-modifying therapy for this condition rather than a treatment that merely manages symptoms. Teduglutide is a 33-amino-acid synthetic analog of glucagon-like peptide-2 (GLP-2); the stored sequence differs from native GLP-2 at position 2, where an alanine has been replaced by glycine — a change that makes the drug resistant to the enzyme DPP-4 and extends its half-life from roughly 7 minutes (native GLP-2) to roughly 2 hours, enabling once-daily use.
History
Teduglutide traces its origins to the discovery of GLP-2 itself. In the mid-1990s Daniel Drucker and colleagues at the University of Toronto identified GLP-2 as a 33-amino-acid intestinal hormone with potent intestinotrophic activity in rodents — meaning it stimulated growth of the intestinal lining. The problem was that native GLP-2 is rapidly degraded by DPP-4 within minutes, making it useless as a drug. NPS Pharmaceuticals (later acquired by Shire, then Takeda) solved this by making a single amino-acid substitution at position 2 (Ala→Gly), creating a DPP-4-resistant analog they called teduglutide (also known by its earlier research designation ALX-0600). Early pharmacokinetic work characterized its safety and half-life in healthy subjects (Jeppesen and colleagues 2005; Koizumi and colleagues 2008), and population PK studies across SBS and Crohn's disease cohorts established its dosing behavior (Yano and colleagues 2009). The STEPS pivotal trial program — a series of Phase 3 randomized controlled trials in adults with short bowel syndrome dependent on parenteral nutrition — demonstrated clinically meaningful reductions in parenteral support requirements at 24 weeks, leading to FDA approval as Gattex in December 2012. A 52-week safety and efficacy extension (STEPS-2) and a long-term follow-up extension (STEPS-3) subsequently supported the durability of the effect. Pediatric controlled trials led to the pediatric label extension in 2019. Teduglutide is also notable for its cost: list prices have historically run into the hundreds of thousands of dollars per patient per year, reflecting rare-disease economics and its status as the only approved disease-modifying therapy for short bowel syndrome.
What it does
Teduglutide acts on the GLP-2 receptor in the intestinal wall, telling the remaining intestinal lining to grow: it increases the height of intestinal villi and the depth of crypts, expanding the absorptive surface area. It also increases blood flow to the intestine and slows gastric emptying, both of which help the gut extract more nutrients and fluid from food. For patients with short bowel syndrome who depend on intravenous nutrition (parenteral nutrition, or PN) to survive, this means the remaining gut becomes more capable — and many patients can progressively reduce the volume, frequency, or duration of their PN infusions. A subset of patients achieve full independence from parenteral nutrition. The effect requires the drug to be present: when teduglutide is stopped, the intestinotrophic stimulus is withdrawn and absorptive capacity regresses over weeks to months, with PN dependence returning toward pre-treatment levels.
Evidence
- Human: Strong. The STEPS pivotal trial (Jeppesen and colleagues, Gastroenterology 2012) demonstrated that significantly more teduglutide-treated adults with SBS achieved a ≥20% reduction in parenteral support volume compared with placebo at 24 weeks. The STEPS-2 52-week extension confirmed sustained benefit. The STEPS-3 long-term extension (Compher and colleagues 2017) documented continued reduction in parenteral nutrition and hydration support with an acceptable safety profile. A Phase 3 RCT in infants and children with SBS-associated intestinal failure (Kocoshis and colleagues 2023) supported the pediatric indication. Post hoc analyses from the STEPS program explored quality of life (Jeppesen and colleagues 2019), mucosal structural adaptation (Jeppesen and colleagues 2013), response predictors (Jeppesen and colleagues 2018), citrulline as a functional marker (Jeppesen and colleagues 2019), and liver chemistries. Multiple systematic reviews and meta-analyses — including a 2022 meta-analysis published in a peer-reviewed nutrition journal and a 2024 network meta-analysis of GLP-2 analogs — have independently synthesized the trial evidence and concluded teduglutide reduces parenteral support requirements in SBS. Exploratory RCTs have examined teduglutide in low-output enterocutaneous fistula and in children with severe acute malnutrition; neither indication is approved, and results remain preliminary.
- Animal: Extensive. GLP-2 biology and intestinal adaptation mechanisms are well-characterized in rodent models and informed the clinical development program.
- In vitro / mechanistic: Strong. GLP-2 receptor signaling on intestinal subepithelial myofibroblasts and downstream growth-factor cascades are thoroughly characterized; see Mechanism below.
Known effects
- Reduction in parenteral nutrition volume and infusion days (SBS with intestinal failure) — FDA-approved; supported by multiple Phase 3 RCTs
- Structural intestinal mucosal adaptation (increased villus height, deeper crypts) — Phase 3 RCT (mucosal-adaptation study; Jeppesen and colleagues 2013)
- Improvement in quality of life in SBS patients — RCT-derived analyses (Jeppesen and colleagues 2013, 2019)
- Improvement in liver chemistries in SBS-associated intestinal failure — Post hoc analysis of randomized data; moderate confidence (single analysis)
- Slowing of gastric emptying — Phase 1 RCT in healthy adults
- Reduction in intestinal permeability and improvement in GI motility — RCT in adult SBS patients on home PN
Safety signals
Adverse events reported consistently across the STEPS trial program and the approved label include abdominal pain, nausea, and injection-site reactions. A defining clinical management issue — rather than a classical adverse event — is fluid overload: as intestinal absorption improves, the volume of parenteral nutrition must be progressively reduced to avoid hypervolemia and electrolyte imbalance; this adjustment is a planned and necessary part of teduglutide management.
The label requires colonoscopy before initiating teduglutide and at intervals during treatment because teduglutide's intestinotrophic mechanism carries a theoretical risk of accelerating growth of colorectal polyps or neoplasia. Long-term colorectal neoplasia risk from chronic intestinotrophic stimulation over years to decades is still being evaluated through postmarketing registries and is not yet fully resolved. Biliary and pancreatic events have been observed and periodic monitoring for biliary and pancreatic disease is part of the labeled clinical management.
The label also identifies active or suspected GI malignancy and active unresected colorectal polyps as conditions requiring careful evaluation before initiating therapy. Known hypersensitivity to teduglutide or its excipients (including trace tetracycline residues from the manufacturing process) is a contraindication. Limited data exist on use in pregnancy and breastfeeding.
Long-term open questions: The long-term pediatric developmental and quality-of-life outcomes in children treated from young ages remain under characterization following the 2019 pediatric label extension. Predictors of full PN independence versus partial response are not yet fully defined. Optimal therapy duration for stable responders — including whether and how to attempt discontinuation — has not been established.
Regulatory status
- US (FDA): Approved prescription drug — Gattex (teduglutide) for adults with short bowel syndrome dependent on parenteral support (December 2012); pediatric indication extended in 2019. Prescription-only; specialty pharmacy dispensing; no compounded or generic supply.
- EU (EMA), UK (MHRA), Canada, Australia: Approved as Revestive for short bowel syndrome; typically managed through national rare-disease drug pathways.
- WADA: Not specifically listed on the WADA Prohibited List. Teduglutide is an intestinotrophic GLP-2 analog rather than a metabolic or anabolic enhancer; athletes prescribed it for SBS should follow appropriate Therapeutic Use Exemption procedures.
- Compounding: No legitimate generic or compounded teduglutide exists. Teduglutide is a complex recombinant peptide manufactured under controlled biologic-product processes, with authorized supply exclusively through the manufacturer's specialty pharmacy.
Myths and misconceptions
- "Teduglutide is a GLP-1 drug like semaglutide or tirzepatide." No. Teduglutide is a GLP-2 analog and acts on the GLP-2 receptor in the intestinal mucosa to stimulate growth of the intestinal lining. GLP-1 drugs act on the GLP-1 receptor to regulate glucose and suppress appetite. GLP-2 and GLP-1 are both derived from the same precursor protein (proglucagon), but they bind different receptors and have completely different pharmacological effects (Gasbjerg and colleagues, Physiological Reviews 2026).
- "Teduglutide is useful for general gut health, leaky gut, or IBS." No. The approved indication is short bowel syndrome with intestinal failure — patients who have lost enough small intestine that they cannot survive without intravenous nutrition. The drug's safety requirements (colonoscopic surveillance, biliary and pancreatic monitoring) and its cost do not support off-label use for milder gastrointestinal conditions.
- "Once a patient responds, they can usually stop taking teduglutide." No. The intestinotrophic effect requires ongoing stimulus. When teduglutide is stopped, villus height and absorptive capacity regress over weeks to months, and PN dependence returns toward pre-treatment levels. Response means continued daily injections, not graduation off the drug.
- "Generic or compounded teduglutide is available at lower cost." No. Teduglutide is a complex recombinant peptide. Authorized supply is exclusively through the manufacturer's specialty pharmacy; there is no legitimate generic or compounded version.
Mechanism
Teduglutide is an agonist at the GLP-2 receptor (GLP-2R), expressed prominently on intestinal subepithelial myofibroblasts. Receptor activation triggers paracrine release of growth factors — keratinocyte growth factor (KGF), insulin-like growth factor 1 (IGF-1), and epidermal growth factor (EGF) — that stimulate crypt cell proliferation and inhibit enterocyte apoptosis, resulting in increased villus height, deeper crypts, and greater mucosal absorptive surface area in the remaining intestine. In addition to these trophic effects, teduglutide increases mesenteric blood flow and reduces gastric motility, both of which support nutrient and fluid absorption.
Mechanistic specificity is important for accurate interpretation: teduglutide acts on the GLP-2 receptor in the intestinal mucosa. It does not act on the GLP-1 receptor that mediates the metabolic and appetite-suppressing effects of semaglutide or tirzepatide. GLP-2 and GLP-1 are co-secreted from the same L cells in the gut and share the proglucagon precursor, but they are pharmacologically distinct — a point reviewed extensively in Gasbjerg and colleagues (Physiological Reviews 2026).
The key structural modification enabling teduglutide's pharmacology: native GLP-2 has an alanine at position 2 that is rapidly cleaved by DPP-4, giving the native hormone a half-life of approximately 7 minutes. Substituting glycine at position 2 (visible as the second residue, G, in the stored sequence HGDGSFSDEMNTILDNLAARDFINWLIQTKITD) renders the peptide DPP-4-resistant and extends half-life to approximately 2 hours, enabling once-daily subcutaneous dosing.
Open questions
- Long-term colorectal neoplasia risk: Postmarketing surveillance and registry data continue to accumulate; cancer risk from decades of chronic intestinotrophic stimulation is not yet fully resolved.
- Pediatric long-term outcomes: Following the 2019 pediatric label extension, longer-term developmental, growth, and quality-of-life outcomes in children treated from young ages are still being characterized.
- Predictors of full PN independence: A subset of patients achieve complete weaning from parenteral nutrition; the clinical, anatomic, and biochemical predictors distinguishing full responders from partial responders are not fully defined (Jeppesen and colleagues, Gastroenterology 2018).
- Optimal therapy duration: Whether and when stable responders should attempt discontinuation — and how to monitor them — is not established.
- Non-SBS indications: Pilot RCT data exist for low-output enterocutaneous fistula and exploratory data exist for severe acute malnutrition; neither indication is approved, and clinical utility outside SBS remains early-stage.
Related peptides
Teduglutide belongs to the proglucagon-derived peptide family, which includes both GLP-1 and GLP-2 and their analogs. For the GLP-1 receptor agonist side of this family — pharmacologically distinct from teduglutide but sharing the same hormonal precursor — see glucagon. GLP-2 biology is reviewed in the context of the broader proglucagon peptide family by Gasbjerg and colleagues (Physiological Reviews 2026), one of the refs attached to this card.
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Could damage to the connective tissue layer beneath the gut lining explain why some short bowel patients get little benefit from teduglutide?
If true, doctors could test for stromal damage before prescribing teduglutide, sparing non-responders an expensive and inconvenient therapy. It might also open the door to pairing teduglutide with drugs that reduce gut scarring.
Could teduglutide help patients with Crohn's disease who have had repeated surgeries and now struggle to absorb nutrients?
If true, many severe Crohn's patients who depend on IV feeding could potentially use this drug to regrow enough gut lining to eat normally again, reducing infection risk and improving quality of life.
Does the key amino acid swap that protects teduglutide from breakdown also make it a stronger activator of its receptor?
If true, it would mean the drug is better than its natural counterpart in two independent ways, and knowing this could help scientists design future gut-repair peptides that are even more effective at lower doses.
Could modifying the loose end of the teduglutide molecule extend its life in the body enough to allow weekly instead of daily injections?
If true, patients with short bowel syndrome could inject the drug once a week rather than every day, which would significantly reduce the burden of managing this already difficult condition and might help more patients stick with their treatment.
Is the drug structurally disordered while circulating, becoming ordered only when it grabs its intestinal receptor?
If true, this could explain how the drug avoids off-target effects while still working powerfully at the gut. It might guide engineers to build tighter, shorter versions of the drug for patients who need lower doses.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8613682985305786 | openfold3-mlx |
| ranking score | 0.9468879699707031 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.763 | global PDE — lower = better |
| disorder | 0.246 | fraction disordered |
| chain pair ipTM (A, B) | 0.861 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | aedd8f3eb814e392… |
| hardware | apple_m4_base_16gb |
| mlx version | 0.31.1 |
| python | 3.14.3 |
| random seed | 42 |
| msa strategy | colabfold |
| diffusion samples | 1 |
| runtime | 650s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-22 |
python3 openfold3/run_openfold.py predict --query_json {query.json} --runner_yaml examples/example_runner_yamls/mlx_runner.yml --output_dir {output_dir} --num_diffusion_samples 1 ▸citationbibtex
@peptide{pep04435,
sequence = {HGDGSFSDEMNTILDNLAARDFINWLIQTKITD},
target = {glp-2r},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}