Cited by 156Diabetes Treatment and ManagementPharmacology and Obesity TreatmentRegulation of Appetite and Obesity

The extra‐pancreatic effects of GLP‐1 receptor agonists: a focus on the cardiovascular, gastrointestinal and central nervous systems

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Seufert, J., Gallwitz, B.·2014·Diabetes, Obesity and Metabolism

Abstract

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”

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Research works printed but not linked: 2

  1. Donnelly R, Emslie-Smith AM, Gardner ID, Morris AD. Vascular complications of diabetes. BMJ 2000; 320: 1062-1066.
  2. review article DIABETES, OBESITY AND METABOLISM 129.

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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
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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