Gut hormones in the treatment of short-bowel syndrome and intestinal failure

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 -