PMID-22982184 – Teduglutide Reduces Parenteral Support in Short Bowel Syndrome
Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O'Keefe SJ. Randomised Placebo-Controlled Trial of Teduglutide in Reducing Parenteral Nutrition and/or Intravenous Fluid Requirements in Patients With Short Bowel Syndrome. Gastroenterology. 2012;143(6):1473-1481.e3.
Quick Reference
| Property | Value |
|---|---|
| PMID | 22982184 |
| DOI | 10.1053/j.gastro.2012.09.007 |
| Year | 2012 |
| Journal | Gastroenterology |
| Study Type | Phase III RCT |
| Evidence Level | I |
| Sample | n=86 adults with SBS-IF (43 teduglutide, 43 placebo) |
| Peptide(s) Studied | GLP-2 |
Key Findings
- Teduglutide 0.05 mg/kg/day subcutaneously significantly reduced parenteral support (PS) volume compared to placebo over 24 weeks (p=0.002)
- 63% of teduglutide-treated patients achieved a clinically meaningful response (>=20% reduction in PS volume) vs 30% on placebo (p=0.002)
- Mean PS volume reduction was 4.4 L/week with teduglutide vs 2.3 L/week with placebo
- Responders showed progressive PS reduction through 24 weeks, suggesting ongoing intestinal adaptation rather than a plateau effect
- Teduglutide was well tolerated; most common adverse events were abdominal pain, nausea, and injection site reactions, generally mild-to-moderate
- This was the pivotal registration trial that led to FDA approval of teduglutide (Gattex) in December 2012 for adults with SBS-IF
Study Design
Multicenter, double-blind, placebo-controlled, parallel-group Phase III RCT conducted across 33 sites in the US, Canada, and Europe. Patients with SBS dependent on parenteral nutrition for >=12 months were randomized 1:1 to teduglutide 0.05 mg/kg/day SC or placebo for 24 weeks. Primary endpoint was the percentage of patients achieving >=20% reduction in weekly PS volume at weeks 20 and 24. PS optimization was standardized at baseline.
Limitations
- Relatively small sample size (n=86) reflecting the rarity of SBS-IF
- 24-week treatment duration may not capture the full trajectory of intestinal adaptation, which can continue for years
- All-comers SBS population with heterogeneous anatomy (varying remnant bowel length, presence/absence of colon-in-continuity), which may mask differential responsiveness
- Did not assess enteral autonomy (complete PS independence) as a primary endpoint
Clinical Relevance
This is the landmark regulatory trial establishing teduglutide as the first and only FDA-approved GLP-2 analog for SBS-IF. It validated the GLP-2 intestinotrophic mechanism in a clinical setting, demonstrating that pharmacological activation of the GLP-2 receptor can promote meaningful intestinal adaptation and reduce dependence on parenteral nutrition. The trial established the 0.05 mg/kg/day dosing standard still used clinically. Essential reference for the GLP-2 peptide profile and for understanding GLP-2's therapeutic niche in intestinal failure.
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#research #RCT #glp-2 #evidence-level-I