T1281 The Influence of Teduglutide, a Novel GLP-2 Analogue, On Energy Absorption in Short Bowel Syndrome (SBS) Patients Dependent On Parenteral Nutrition (PN)

Abstract

Given the disabling clinical conditions and healthcare burden associated with intestinal failure, therapies to enhance intestinal function could reduce PN dependence of afflicted individuals. Teduglutide (TG), a degradation resistant analog of the intestinaltrophic peptide glucagon-like peptide-2, is a potential candidate for PN-dependent SBS patients. Background: PN-dependent SBS patients are at risk of serious long-term complications and therapies to improve gut function are limited. The GLP-2 analogue teduglutide (TG) reduced PN volumes in PN-dependent SBS patients in a 24-week placebo-controlled study. Aim: A 72-hour balance sub-study was conducted to quantify the ability of teduglutide to increase energy absorption. Methods: At baseline, weeks 8 and 24, patients recorded food and beverages consumed, based on their standard diets. Energy in diet and feces was measured by bomb calorimetry. Absolute energy absorption was calculated as the difference between oral intake and fecal excretion. Relative energy absorption was determined as the absolute absorption divided by oral intake multiplied by 100. SBS patients received daily sc injections of 4 placebo, 10 teduglutide 0.05 mg/kg/d or 7 teduglutide 0.10 mg/kg/d. Ten were male, 50±14 years, post duodenal remnant small bowel 57±44cm, 14 with 70±21% remnant colon and PN for 7±6 years. Results: Complete data sets were obtained in 14 of the 21 pts (3 placebo, 6 TG 0.05 mg/kg/d and 5 TG 0.10mg/kg/d). No significant changes were seen in the placebo group. The pooled teduglutide groups (n=11) demonstrated a reduction in fecal energy excretion of 220±270 kcal at week 24 (p=0.026), but no significant increase in the overall energy absorption (80±500 kcal/d, p=0.49) because energy intake did not remain constant. However, in those whose dietary energy content did not differ by more than 10% from baseline values (High Dietary Compliance~HDC), fecal energy excretion decreased and intestinal absorption increased significantly (p<0.05) at week 8 and at week 24 compared to baseline. Conclusion: After 6 month's treatment, teduglutide significantly increased energy absorption in PN-dependent SBS patients provided their dietary intake remained constant. These data merit further evaluation in larger patient populations.