Short Bowel Syndrome
A condition caused by surgical removal or disease of a large portion of the small intestine, leading to malabsorption requiring parenteral nutrition. Teduglutide (a GLP-2 analogue) promotes intestinal adaptation, reducing dependence on intravenous feeding. Holds orphan drug designation.
Technical Context
SBS results from extensive small bowel resection (most commonly for Crohn's disease, mesenteric ischaemia, or radiation enteritis) leaving insufficient intestinal length for adequate nutrient/fluid absorption. Classification by anatomy: end-jejunostomy (most severe — no colon, highest fluid losses), jejuno-colonic anastomosis (colon present — better fluid absorption but risk of oxalate kidney stones), and jejuno-ileal anastomosis (least severe). Intestinal adaptation occurs naturally over 1-2 years: villus hyperplasia, crypt deepening, increased absorptive surface area. Teduglutide mechanism: GLP-2R activation → increased intestinal villus height (+30-50% in animal models), crypt depth, intestinal blood flow, and nutrient transporter expression. STEPS and STEPS-2 trials: teduglutide 0.05mg/kg daily SC → significant reduction in parenteral nutrition volume (≥20% reduction in approximately 63% vs 30% placebo at 24 weeks; some patients achieved complete PN independence). Treatment duration is indefinite — benefits reverse upon discontinuation. Cost: approximately $300,000/year (justified by comparison to PN costs of $100,000-200,000/year plus PN-associated complications).