Comparative Effects of Prolonged and Intermittent Stimulation of the Glucagon-Like Peptide 1 Receptor on Gastric Emptying and Glycemia
- Mahesh M. Umapathysivam1,
- Michael Y. Lee1,
- Karen L. Jones2,
- Christopher E. Annink3,
- Caroline E. Cousins3,
- Laurence G. Trahair2,
- Chris K. Rayner2,
- Marianne J. Chapman1,3,
- Michael A. Nauck4,
- Michael Horowitz2 and
- Adam M. Deane1,3⇑
- 1Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia
- 2Discipline of Medicine, University of Adelaide, Adelaide, Australia
- 3Department of Critical Care Services, Royal Adelaide Hospital, Adelaide, Australia
- 4Diabeteszentrum Bad Lauterberg, Bad Lauterberg, Germany
- Corresponding author: Adam M. Deane, .
Acute administration of glucagon-like peptide 1 (GLP-1) and its agonists slows gastric emptying, which represents the major mechanism underlying their attenuation of postprandial glycemic excursions. However, this effect may diminish during prolonged use. We compared the effects of prolonged and intermittent stimulation of the GLP-1 receptor on gastric emptying and glycemia. Ten healthy men received intravenous saline (placebo) or GLP-1 (0.8 pmol/kg ⋅ min), as a continuous 24-h infusion (“prolonged”), two 4.5-h infusions separated by 20 h (“intermittent”), and a 4.5-h infusion (“acute”) in a randomized, double-blind, crossover fashion. Gastric emptying of a radiolabeled mashed potato meal was measured using scintigraphy. Acute GLP-1 markedly slowed gastric emptying. The magnitude of the slowing was attenuated with prolonged but maintained with intermittent infusions. GLP-1 potently diminished postprandial glycemia during acute and intermittent regimens. These observations suggest that short-acting GLP-1 agonists may be superior to long-acting agonists when aiming specifically to reduce postprandial glycemic excursions in the treatment of type 2 diabetes.
Clinical trial reg. no. ACTRN12612001035819, www.anzctr.org.au.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0893/-/DC1.
See accompanying commentary, p. 407.
- Received June 7, 2013.
- Accepted September 23, 2013.
- © 2014 by the American Diabetes Association.
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