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

BACKGROUND AND AIMS:

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.

CONCLUSION:

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: K B Madsen, C Askov-Hansen, R M Naimi, C F Brandt, B Hartmann, J J Holst, P B Mortensen, P B Jeppesen
• Journal: Regulatory peptides (Regul Pept) Vol. 184 Pg. 30-9 (Jun 10 2013) ISSN: 1873-1686 [Electronic] Netherlands
• PMID: 23511332 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Blood Glucose
• C-Peptide
• Glucagon-Like Peptide 2
• Placebos
• Glucagon-Like Peptide 1

Topics

• Blood Glucose
• C-Peptide (blood)
• Drug Therapy, Combination
• Female
• Glucagon-Like Peptide 1 (pharmacology, therapeutic use)
• Glucagon-Like Peptide 2 (pharmacology, therapeutic use)
• Humans
• Intestinal Absorption (drug effects)
• Male
• Middle Aged
• Placebos
• Short Bowel Syndrome (drug therapy, metabolism)