Comparative effects of prolonged and intermittent stimulation of the glucagon-like peptide-1 receptor on gastric emptying and glycaemia
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 glycaemia.
Ten healthy men received intravenous saline (‘placebo’) or GLP-1 (0.8 pmol/kg.min), as a continuous 24h infusion (‘prolonged’), two 4.5h infusions separated by 20h (‘intermittent’), and a 4.5h infusion (‘acute’), in 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 glycaemia 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.
- Received June 7, 2013.
- Accepted September 23, 2013.
- © 2013 by the American Diabetes Association.
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