TY - JOUR
T1 - Gut hormones in the treatment of short-bowel syndrome and intestinal failure
AU - Jeppesen, Palle B
PY - 2015/2/13
Y1 - 2015/2/13
N2 - PURPOSE OF REVIEW: The approval of teduglutide, a recombinant analog of human glucagon-like peptide (GLP) 2, by the US Food and Drug Administration (Gattex) and the European Medicines Agency (Revestive) has illustrated the potential of selected gut hormones as treatments in patients with short-bowel syndrome and intestinal failure. Gut hormones may improve the structural and functional intestinal adaptation following intestinal resection by decreasing a rapid gastric emptying and hypersecretion, by increasing the intestinal blood flow, and by promoting intestinal growth. This review summarizes the findings from phase 2 and 3 teduglutide studies, and pilot studies employing GLP-1 and agonists for this orphan condition.RECENT FINDINGS: In a 3-week, phase 2, metabolic balance study, teduglutide increased the intestinal wet weight absorption by approximately 700 g/day and reduced fecal energy losses by approximately 0.8 MJ/day (∼200 Kcal/day). In two subsequent 24-week, phase 3 studies, teduglutide reduced the need for parenteral support in the same magnitude. Adverse events were mainly of gastrointestinal origin and consistent with the known mechanism of action of teduglutide. Pilot studies suggest that GLP-1 may be less potent. Synergistic effects may be seen by co-treatment with GLP-2.SUMMARY: Gut hormones promote intestinal adaptation and absorption, decreasing fecal losses, thereby decreasing or even eliminating the need for parenteral support. This will aid the intestinal rehabilitation in these severely disabled short-bowel syndrome patients.
AB - PURPOSE OF REVIEW: The approval of teduglutide, a recombinant analog of human glucagon-like peptide (GLP) 2, by the US Food and Drug Administration (Gattex) and the European Medicines Agency (Revestive) has illustrated the potential of selected gut hormones as treatments in patients with short-bowel syndrome and intestinal failure. Gut hormones may improve the structural and functional intestinal adaptation following intestinal resection by decreasing a rapid gastric emptying and hypersecretion, by increasing the intestinal blood flow, and by promoting intestinal growth. This review summarizes the findings from phase 2 and 3 teduglutide studies, and pilot studies employing GLP-1 and agonists for this orphan condition.RECENT FINDINGS: In a 3-week, phase 2, metabolic balance study, teduglutide increased the intestinal wet weight absorption by approximately 700 g/day and reduced fecal energy losses by approximately 0.8 MJ/day (∼200 Kcal/day). In two subsequent 24-week, phase 3 studies, teduglutide reduced the need for parenteral support in the same magnitude. Adverse events were mainly of gastrointestinal origin and consistent with the known mechanism of action of teduglutide. Pilot studies suggest that GLP-1 may be less potent. Synergistic effects may be seen by co-treatment with GLP-2.SUMMARY: Gut hormones promote intestinal adaptation and absorption, decreasing fecal losses, thereby decreasing or even eliminating the need for parenteral support. This will aid the intestinal rehabilitation in these severely disabled short-bowel syndrome patients.
KW - Clinical Trials, Phase II as Topic
KW - Gastrointestinal Agents
KW - Glucagon-Like Peptide 1
KW - Humans
KW - Intestinal Absorption
KW - Intestine, Small
KW - Parenteral Nutrition
KW - Peptides
KW - Pilot Projects
KW - Quality of Life
KW - Short Bowel Syndrome
KW - United States
U2 - 10.1097/MED.0000000000000120
DO - 10.1097/MED.0000000000000120
M3 - Review
C2 - 25485516
SN - 1752-296X
VL - 22
SP - 14
EP - 20
JO - Current Opinion in Endocrinology, Diabetes and Obesity
JF - Current Opinion in Endocrinology, Diabetes and Obesity
IS - 1
ER -