Comparative Effects of Prolonged and Intermittent Stimulation of the Glucagon-Like Peptide 1 Receptor on Gastric Emptying and Glycemia
Open accessAbstract
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.
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Tachyphylaxis occurs with prolonged use of GLP-1 RAs.
“Data also suggest that there is tachyphylaxis with prolonged use of GLP‐1 RAs [29, 60]”
The Discussion reports tachyphylaxis specifically in GLP-1’s effect on gastric emptying after prolonged receptor stimulation in healthy volunteers, and says the gastric-emptying effect of long-acting agonists appears to diminish with ongoing use. It does not establish tachyphylaxis of GLP-1 receptor agonists’ effects generally during prolonged treatment; the Discussion notes that islet-cell effects may not show it. (LLM, conf=0.85)
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- Authors
- Umapathysivam, M. M., Lee, M. Y., Jones, K. L., Annink, C. E., Cousins, C. E., Trahair, L. G., Rayner, C. K., Chapman, M. J., Nauck, M. A., Horowitz, M., & Deane, A. M.
- Affiliations
- The University of Adelaide (AU)
- Royal Adelaide Hospital (AU)
- Discipline of Medicine, University of Adelaide, Adelaide, Australia
- Diabeteszentrum Bad Lauterberg (DE)
- Corresponding author
- Deane, Adam M.
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2014-01-16
- Volume
- 63
- Issue
- 2
- Pages
- 785-790
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3900552
- OpenAlex
- W2127782831
- Cited by
- 193
- References
- 29
- Citations by year
- 2026: 20 · 2025: 22 · 2024: 33 · 2023: 18 · 2022: 7 · 2021: 10 · 2020: 15 · 2019: 9 · 2018: 7 · 2017: 12 · 2016: 14 · 2015: 11 · 2014: 12 · 2013: 2
- FWCI
- 10.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- glucagon-like peptide-1, GLP-1 receptor, gastric emptying, glycemia, postprandial glycemic excursions, GLP-1 receptor agonists, type 2 diabetes
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Blood Glucose, Double-Blind Method, Gastric Emptying, Glucose, Humans, Insulin, Male, Receptors, Glucagon, Cross-Over Studies, Area Under Curve, Glucagon-Like Peptide 1, Young Adult
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