The role of glucagon‐like peptide‐1 impairment in obesity and potential therapeutic implications
Abstract
The hormone glucagon‐like peptide‐1 ( GLP ‐1) is released from the gut in response to food intake. It acts as a satiety signal, leading to reduced food intake, and also as a regulator of gastric emptying. Furthermore, GLP ‐1 functions as an incretin hormone, stimulating insulin release and inhibiting glucagon secretion from the pancreas in response to food ingestion. Evidence suggests that the action or effect of GLP ‐1 may be impaired in obese subjects, even in those with normal glucose tolerance. GLP ‐1 impairment may help explain the increased gastric emptying and decreased satiety signalling seen in obesity. Incretin impairment, probably associated with reduced insulinotropic potency of GLP ‐1, is also characteristic of type 2 diabetes (T2D). Therefore, it is possible that incretin impairment may contribute to the pathophysiological bridge between obesity and T2D. This review summarises current knowledge about the pathophysiology and consequences of GLP ‐1 and incretin impairment in obesity, and examines the evidence for an incretin‐related link between obesity and T2D. It also considers the current literature surrounding the novel use of GLP ‐1 receptor agonists as a treatment for obesity in patients with normoglycaemia, prediabetes and T2D.
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Postprandial GLP‐1 secretion is increased in obese patients following bariatric surgery and correlates with weight loss maintenance.
“Interestingly, postprandial glucagon‐like peptide‐1 (GLP‐1) secretion is increased in obese patients following bariatric surgery and correlates with weight loss maintenance 139.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [139]
A reduced incretin effect is seen in subjects with type 2 diabetes (T2D) and obesity.
“Moreover, a reduced incretin effect is seen in subjects with type 2 diabetes (T2D) and obesity.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [139]
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DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., Hu, F. B., Kahn, C. R., Raz, I., Shulman, G. I., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.19 · Cited by 2,611 · see citing works
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“Glucagon-like peptide-1 (GLP-1) is a gut hormone released in response to food intake that acts as a satiety signal, stimulates insulin release, inhibits glucagon secretion, and regulates gastric emptying.(10,11) In addition, GLP-1 has other effects that are potentially beneficial from a cardiovascular risk perspective…”
BackgroundAcute Exercise and Hormones Related to Appetite Regulation: A Meta-Analysis
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Self-citationTreatment potential of the GLP-1 receptor agonists in type 2 diabetes mellitus: a review
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Self-citationPotential contributors to variation in weight‐loss response to liraglutide
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- Authors
- Madsbad, S.
- Affiliations
- Hvidovre Hospital (DK)
- Corresponding author
- Madsbad, S.
- ORCID
- Madsbad, S.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2013-05-26
- Volume
- 16
- Issue
- 1
- Pages
- 9-21
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W1988527243
- Cited by
- 146
- References
- 155
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 6 · 2023: 12 · 2022: 13 · 2021: 8 · 2020: 11 · 2019: 7 · 2018: 16 · 2017: 12 · 2016: 12 · 2015: 13 · 2014: 20 · 2013: 3 · 2012: 1
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- glucagon-like peptide-1, GLP-1 receptor agonists, obesity, type 2 diabetes, gastric emptying, insulin secretion, glucagon secretion, prediabetes, obesity treatment
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Insulin Secretion, Blood Glucose, Diabetes Mellitus, Type 2, Gastric Emptying, Gastrointestinal Motility, Humans, Insulin, Obesity, Satiation, Receptors, Glucagon, Glucagon-Like Peptide 1, Incretins
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