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Exenatide Exerts a Potent Antiinflammatory Effect
Open accessAbstract
OBJECTIVE: Our objective was to determine whether exenatide exerts an antiinflammatory effect. RESEARCH DESIGN AND METHODS: Twenty-four patients were prospectively randomized to be injected sc with either exenatide 10 μg twice daily [n = 12; mean age = 56 ± 3 yr; mean body mass index = 39.8 ± 2 kg/m(2); mean glycosylated hemoglobin (HbA1c) = 8.6 ± 0.4%] or placebo twice daily (n = 12; mean age = 54 ± 4 yr; mean body mass index = 39.1 ± 1.6 kg/m(2); mean HbA1c = 8.5 ± 0.3%) for 12 wk. Fasting blood samples were obtained at 0, 3, 6, and 12 wk. Blood samples were also collected for up to 6 h after a single dose of exenatide (5 μg) or placebo. RESULTS: Fasting blood glucose fell from 139 ± 17 to 110 ± 9 mg/dl, HbA1c from 8.6 ± 0.4 to 7.4 ± 0.5% (P < 0.05), and free fatty acids by 21 ± 5% from baseline (P < 0.05) with exenatide. There was no weight loss. There was a significant reduction in reactive oxygen species generation and nuclear factor-κB binding by 22 ± 9 and 26 ± 7%, respectively, and the mRNA expression of TNFα, IL-1β, JNK-1, TLR-2, TLR-4, and SOCS-3 in mononuclear cells by 31 ± 12, 22 ± 10, 20 ± 11, 22 ± 9, 16 ± 7, and 31 ± 10%, respectively (P < 0.05 for all) after 12 wk of exenatide. After a single injection of exenatide, there was a reduction by 20 ± 7% in free fatty acids, 19 ± 7% in reactive oxygen species generation, 39 ± 11% in nuclear factor-κB binding, 18 ± 9% in TNFα expression, 26 ± 7% in IL-1β expression, 18 ± 7% in JNK-1 expression, 24 ± 12% in TLR-4 expression, and 23 ± 11% in SOCS-3 expression (P < 0.05 for all). The plasma concentrations of monocyte chemoattractant protein-1, matrix metalloproteinase-9, serum amyloid A, and IL-6 were suppressed after 12 wk exenatide treatment by 15 ± 7, 20 ± 11, 16 ± 7, and 22 ± 12%, respectively (P < 0.05 for all). CONCLUSIONS: Exenatide exerts a rapid antiinflammatory effect at the cellular and molecular level. This may contribute to a potentially beneficial antiatherogenic effect. This effect was independent of weight loss.
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“Separately, exenatide inhibited binding of NF-κB to DNA and downregulated TNF and IL1B in human PBMCs (23).”
From Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits (2025) · cites this paper as [23]
In the citing paper
“For instance, in a placebo-controlled study of 24 obese patients with T2DM, exenatide treatment for 12 weeks exerted an anti-inflammatory effect independent of body weight reduction, as illustrated by reduced circulating levels of various pro-inflammatory mediators such as TNF-α, IL-1β, IL-6, serum amyloid A, and MMP-9 [79].”
From Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms (2022) · cites this paper as [79]
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“These animal data are in line with findings from human studies [57, 79–81].”
From Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms (2022) · cites this paper as [79]
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“dysfunction of endothelial cells, induced by hyperglycemia and driven by this systemic proinflammatory state, trigger cardiomyocyte dysfunction in HFpEF.”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [65]
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Metadata
- Authors
- Chaudhuri, A., Ghanim, H., Vora, M., Sia, C. L., Korzeniewski, K., Dhindsa, S., Makdissi, A., & Dandona, P.
- Affiliations
- University at Buffalo, State University of New York (US)
- Kaleida Health (US)
- Corresponding author
- Dandona, Paresh
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-01
- Volume
- 97
- Issue
- 1
- Pages
- 198-207
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3251936
- OpenAlex
- W2055611619
- Cited by
- 284
- References
- 38
- Citations by year
- 2026: 26 · 2025: 35 · 2024: 20 · 2023: 25 · 2022: 27 · 2021: 16 · 2020: 12 · 2019: 16 · 2018: 17 · 2017: 14 · 2016: 18 · 2015: 12 · 2014: 16 · 2013: 18 · 2012: 12
- FWCI
- 12.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health (5r01dk069805-04)
- University at Buffalo
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK069805, R01DK075877)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- exenatide, anti-inflammatory activity, type 2 diabetes, NF-κB, reactive oxygen species, free fatty acids, TNF-α, IL-1β, TLR2, TLR4, JNK1, SOCS3, mononuclear cells, blood glucose, HbA1c, GLP-1 receptor agonists
- MeSH terms
- Exenatide, Anti-Inflammatory Agents, Blood Glucose, Diabetes Mellitus, Type 2, Drug Administration Schedule, Fatty Acids, Nonesterified, Humans, Hypoglycemic Agents, Insulin, Middle Aged, Obesity, Peptides, Placebos, Time Factors, Venoms, Single-Blind Method, Treatment Outcome, Reactive Oxygen Species
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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