title: Acute effects of continuous infusions of glucagon-like peptide (GLP)-1, GLP-2 and the combination (GLP-1+GLP-2) on intestinal absorption in short bowel syndrome (SBS) patients. A placebo-controlled study.
abstract: OBJECTIVE
  The ileocolonic brake is impaired in short bowel syndrome (SBS) patients with distal bowel resections. An attenuated meal-stimulated hormone secretion may cause gastric hypersecretion, rapid gastric and intestinal transit and a poor adaptation. Attempting to restore this ileocolonic brake, this study evaluated the acute effects of continuous intravenous administration of glucagon-like peptide (GLP) 1 and 2, alone or in combination, on gastrointestinal function in SBS patients.
  
  
  METHODS
  SBS patients were admitted 4 times for identical 72-h balance studies, where infusions (1 pmol/kg/min) of GLP-1, placebo (saline), GLP-2 and GLP-1+2 (1 pmol/kg/min of each), were provided. Patients filled out a VAS questionnaire regarding subjective symptoms during treatments. Bone mineral content, body-weight and -composition were measured using DEXA scans. Blood glucose, insulin, pro insulin C-peptide and GLP concentrations were measured in relation to a standardized breakfast.
  
  
  RESULTS
  Nine SBS patients (5 women/4 men, aged 52±11) were enrolled and completed the study; 7 had end-jejunostomies, 2 had 50% of colon-in-continuity. All treatments significantly reduced the fecal wet weight, energy, nitrogen, sodium and potassium losses compared to placebo. However, only GLP-2 containing treatments increased absolute absorption of wet weight and sodium. Only GLP-1+2 improved the hydrational status evaluated by DEXA increases in the fat mass and calculated total body weight. GLP-1 and GLP-1+2 reduced the post-prandial blood glucose levels. A tendency of nausea and reduced appetite was seen in relation to GLP-1 treatment, but this was ameliorated by the co-administration of GLP-2.
  
  
  CONCLUSIONS
  GLP-1 decreased diarrhea and fecal excretions in SBS patients, but it seems less potent than GLP-2. The combination of GLP-1+2 numerically provided additive effects on intestinal absorption compared to either peptide given alone. Larger, long-term studies should further assess the potential of the glucagon-like peptides or analogs, alone or in combination, in the treatment of SBS patients.
authors.affiliation: Department of Gastroenterology CA-2121, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: K B
authors.initials: KB
authors.lastname: Madsen
authors.forename: C
authors.initials: C
authors.lastname: Askov-Hansen
authors.forename: R M
authors.initials: RM
authors.lastname: Naimi
authors.forename: C F
authors.initials: CF
authors.lastname: Brandt
authors.forename: B
authors.initials: B
authors.lastname: Hartmann
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: P B
authors.initials: PB
authors.lastname: Mortensen
authors.forename: P B
authors.initials: PB
authors.lastname: Jeppesen
mesh_terms: D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology* / Q000627:therapeutic use; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012778:Short Bowel Syndrome / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D053767:Glucagon-Like Peptide 2; D010919:Placebos; D052216:Glucagon-Like Peptide 1