The extra‐pancreatic effects of GLP‐1 receptor agonists: a focus on the cardiovascular, gastrointestinal and central nervous systems
Open accessAbstract
The glucagon‐like peptide‐1 receptor agonists ( GLP‐1RAs ) exenatide, liraglutide and lixisenatide have been shown to improve glycaemic control and beta‐cell function with a low risk of hypoglycaemia in people with type 2 diabetes. GLP ‐1 receptors are also expressed in extra‐pancreatic tissues and trial data suggest that GLP‐1RAs also have effects beyond their glycaemic actions. Preclinical studies using native GLP ‐1 or GLP‐1RAs provide substantial evidence for cardioprotective effects, while clinical trial data have shown beneficial actions on hypertension and dyslipidaemia in people with type 2 diabetes. Significant weight loss has been reported with GLP‐1RAs in both people with type 2 diabetes and obese people without diabetes. GLP‐1RAs also slow down gastric emptying, but preclinical data suggest that the main mechanism behind GLP‐1RA ‐induced weight loss is more likely to involve their effects on appetite signalling in the brain. GLP‐1RAs have also been shown to exert a neuroprotective role in rodent models of stroke, Alzheimer's disease and Parkinson's disease. These extra‐pancreatic effects of GLP‐1RAs could provide multi‐factorial benefits to people with type 2 diabetes. Potential adverse effects of GLP‐1RA treatment are usually manageable but may include gastrointestinal effects, increased heart rate and renal injury. While extensive further research is still required, early data suggest that GLP‐1RAs may also have the potential to favourably impact cardiovascular disease, obesity or neurological disorders in people without diabetes in the future.
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In the context of T2DM, GLP-1RAs have produced a range of beneficial pancreatic impacts, leading to significant enhancements in HbA1c, fasting and postprandial plasma glucose levels, and pancreatic beta-cell performance indicators.
“In the context of T2DM, GLP-1RAs have produced a range of beneficial pancreatic impacts, leading to significant enhancements in glycated hemoglobin (HbA1c), fasting and postprandial plasma glucose levels, and pancreatic beta-cell performance indicators.72–74”
From Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications (2024) · cites this paper as [74]
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Flagged first, then by citations
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- Authors
- Seufert, J., & Gallwitz, B.
- Affiliations
- University of Freiburg (DE)
- University of Tübingen (DE)
- Corresponding author
- Seufert, J.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2014-01-16
- Volume
- 16
- Issue
- 8
- Pages
- 673-688
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2005088542
- Cited by
- 156
- References
- 136
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 23 · 2023: 9 · 2022: 11 · 2021: 8 · 2020: 7 · 2019: 9 · 2018: 12 · 2017: 12 · 2016: 15 · 2015: 12 · 2014: 7
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- GLP-1 receptor agonists, exenatide, liraglutide, lixisenatide, type 2 diabetes, cardioprotection, hypertension, dyslipidemia, weight loss, gastric emptying, neuroprotection, stroke, Alzheimer's disease, Parkinson's disease, gastrointestinal adverse effects, kidney injury, cardiovascular disease, obesity
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-2 Receptor, Liraglutide, Exenatide, Animals, Diabetes Mellitus, Type 2, Diabetic Neuropathies, Gastrointestinal Diseases, Humans, Hypoglycemic Agents, Obesity, Peptides, Venoms, Receptors, Glucagon, Evidence-Based Medicine, Diabetes Complications, Glucagon-Like Peptide 1, Incretins, Diabetic Cardiomyopathies
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