Peptide Schedule
Teduglutide (Gattex/Revestive)33 residuesHGDGSFSDEMNTILDNLAARDFINWLIQTKITDEach bubble = one amino acid. Size = residue mass. Color = chemical class.Teduglutide (Gattex/Revestive)
Benefits
About Teduglutide (Gattex/Revestive)
Teduglutide (brand names Gattex in the US, Revestive in Europe) is an FDA-approved recombinant analog of glucagon-like peptide-2 (GLP-2) manufactured by Takeda for the treatment of adults and pediatric patients (1 year and older) with short bowel syndrome (SBS) who are dependent on parenteral support. It is a 33-amino acid peptide identical to native human GLP-2 except for a single substitution at position 2 (glycine replaced with alanine), which confers resistance to dipeptidyl peptidase-IV (DPP-IV) cleavage and extends the half-life to approximately 2 hours — enabling once-daily subcutaneous dosing. In the pivotal STEPS trial, 63% of patients receiving teduglutide 0.05 mg/kg/day achieved a clinically meaningful 20-100% reduction in parenteral support volume at 24 weeks, compared with 30% on placebo (p=0.002). Long-term extension studies (STEPS-2 and STEPS-3) demonstrated sustained reductions in parenteral nutrition requirements over 2+ years of continuous treatment.
Who Should Consider Teduglutide (Gattex/Revestive)
- Adults with short bowel syndrome-associated intestinal failure dependent on parenteral support
- Pediatric patients (≥1 year) with SBS-associated intestinal failure requiring parenteral support
- Post-surgical SBS patients following massive intestinal resection
- Patients with Crohn's disease-related SBS requiring parenteral nutrition
- SBS patients seeking to reduce hours of parenteral support and improve quality of life
- Patients with intact colon-in-continuity (higher response rates observed in this subgroup)
How Teduglutide (Gattex/Revestive) Works
Teduglutide is a GLP-2 receptor agonist. It binds to GLP-2 receptors expressed on intestinal subepithelial myofibroblasts and enteric neurons, triggering a cascade of trophic signals that drive intestinal mucosal growth. The single amino acid substitution (Gly2→Ala) at position 2 renders it resistant to DPP-IV enzymatic degradation, extending its half-life from ~7 minutes (native GLP-2) to ~2 hours. Upon GLP-2 receptor activation, teduglutide stimulates crypt cell proliferation, increases villus height and crypt depth, enhances mesenteric blood flow via nitric oxide-dependent vasodilation, upregulates nutrient transporter expression, and strengthens intestinal epithelial tight junctions to improve barrier function. It also slows gastric emptying and reduces gastric acid secretion, further optimizing nutrient absorption in the shortened bowel. The net effect is a clinically meaningful increase in intestinal absorptive capacity that reduces or eliminates dependence on parenteral nutrition.
What to Expect
Treatment initiation at 0.05 mg/kg/day. GI side effects (abdominal pain, nausea, distension) are most common early and typically mild-moderate. Parenteral support volumes are maintained while intestinal adaptation begins. Plasma citrulline levels may start rising, indicating enterocyte mass expansion.
Intestinal absorption capacity begins increasing measurably. First parenteral support volume reductions (10-20%) may be attempted based on urine output monitoring. Villus height and crypt depth begin increasing. GI side effects generally stabilize or improve.
Peak response period aligned with the STEPS trial endpoint. 63% of patients achieve ≥20% reduction in weekly parenteral support volume. Some patients may achieve complete days off parenteral nutrition. Lean body mass and nutritional markers improve. Continued monitoring for fluid balance is essential.
Sustained and often progressive reductions in parenteral support. STEPS-2 data show continued improvement beyond 24 weeks. Some patients achieve enteral autonomy (complete freedom from parenteral nutrition). Colonoscopy surveillance should be scheduled per protocol.
Long-term maintenance therapy with sustained benefits. STEPS-3 data confirm durability of response over 30+ months. Parenteral support reductions are maintained. Ongoing monitoring includes biannual lipase/amylase and periodic colonoscopy. Regression of adaptation occurs if therapy is discontinued.
Dosing Protocol
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 2,500mcg | Daily |
| Moderate | 3,500mcg | Daily |
| Aggressive | 5mg | Daily |
Note: FDA-approved GLP-2 analog for short bowel syndrome-associated intestinal failure. Weight-based dosing at 0.05 mg/kg/day SC. Supplied as 5mg lyophilized powder; reconstitute with 0.5mL sterile water for injection (10 mg/mL). Reduce dose to 0.025 mg/kg/day in patients with moderate-to-severe renal impairment (eGFR <60). Colonoscopy required within 6 months before starting treatment and at least every 5 years thereafter.
How to Inject Teduglutide (Gattex/Revestive)
Administer 0.05 mg/kg once daily via subcutaneous injection. Reconstitute a single 5mg vial with 0.5mL preservative-free sterile water for injection to yield a 10 mg/mL solution. Gently roll the vial — do not shake. Allow to stand for 30 seconds, then draw up the calculated dose volume. Inject subcutaneously into the abdomen (alternating quadrants), thigh, or upper arm. Rotate injection sites daily. Reduce dose to 0.025 mg/kg/day for patients with moderate-to-severe renal impairment (CrCl <60 mL/min) or end-stage renal disease. Discard any unused reconstituted solution.
Cycling Protocol
Teduglutide is used continuously as a chronic therapy. There is no cycling protocol — the drug is administered daily without breaks. Discontinuation leads to regression of intestinal adaptation within weeks. Regular colonoscopy surveillance and lipase/amylase monitoring every 6 months are required during ongoing therapy. Clinical reassessment of parenteral support needs should occur at least every 6 months.
Pharmacokinetics
Source: FDA Prescribing Information (Gattex), Section 12.3; Marier et al. J Clin Pharmacol 2010 PMID:19773525
Loading the interactive decay curve.
Side Effects
The most common adverse reactions (≥10%) include abdominal pain, nausea, upper respiratory tract infection, abdominal distension, injection site reactions, vomiting, fluid overload, and hypersensitivity. Headache affects approximately 35% and nausea about 31% in long-term use. Serious but less common risks include intestinal obstruction (due to trophic mucosal effects), biliary and pancreatic disease (requires lipase/amylase monitoring every 6 months), and acceleration of neoplastic growth (colonoscopy surveillance required). Fluid overload and congestive heart failure have been reported. Nephrolithiasis has emerged as a post-marketing signal. Side effects are generally mild to moderate and comparable between treatment and placebo groups.
Contraindications
- Active gastrointestinal malignancy (GI cancer) — teduglutide is contraindicated due to risk of accelerating neoplastic growth
- Active or suspected intestinal obstruction — trophic mucosal effects may worsen obstruction
- History of GI malignancy within the past 5 years — requires careful risk assessment
- Known hypersensitivity to teduglutide or any component of the formulation
- Colorectal polyps detected on baseline colonoscopy should be removed before initiating therapy
- Pregnancy and breastfeeding — teratogenic effects observed in animal studies; use only if benefit outweighs risk
- Biliary or pancreatic disease — use with caution; requires baseline and periodic monitoring of lipase, amylase, and bilirubin
Drug Interactions
- Oral medications with narrow therapeutic index — teduglutide increases intestinal absorption and may raise serum levels of concomitant oral drugs; dose adjustments may be needed
- Benzodiazepines and other CNS depressants — increased oral absorption may potentiate sedative effects
- Oral anticoagulants (warfarin) — enhanced absorption may increase INR; monitor closely
- Immunosuppressants (cyclosporine, tacrolimus) — enhanced absorption may increase toxicity risk; monitor drug levels
- Diuretics and fluid-balance medications — as intestinal absorption improves, parenteral fluid needs decrease; adjust accordingly to avoid fluid overload
- Thyroid medications (levothyroxine) — absorption may be altered; monitor TSH levels
Storage & Stability
Molecular Profile
Related Peptides
References
- Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndromePubMed 21317170
- Long-Term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Short Bowel Syndrome (STEPS-2)PubMed 26844839
- Reduction of Parenteral Nutrition and Hydration Support and Safety With Long-Term Teduglutide Treatment in Patients With Short Bowel Syndrome-Associated Intestinal Failure: STEPS-3 StudyPubMed 29761915
- Teduglutide for the treatment of adults with intestinal failure associated with short bowel syndrome: pooled safety data from four clinical trialsPubMed 32341691
- Population pharmacokinetics of teduglutide following repeated subcutaneous administrations in healthy participants and in patients with short bowel syndrome and Crohn's diseasePubMed 19773525
- Gattex (Teduglutide) FDA Prescribing InformationFDA Label