Effects of GLP-1 receptor agonists on myokine levels and pro-inflammatory cytokines in patients with type 2 diabetes mellitus
Abstract
Background and aims To evaluate the change in circulating serum irisin and interleukin-6 (IL-6), in patients with type 2 diabetes mellitus (T2DM) after 6 and 12 months of GLP-1 treatment. Methods and results Eighty-five patients with T2DM inadequately controlled with insulin or other hypoglycaemic drugs were added to dulaglutide (N° = 44) and liraglutide (N° = 41) treatment. After 6 months of GLP-1 analogues a significant decrease in BMI (p < 0.001), waist circumference (WC) (p < 0.001), fasting blood glucose (p < 0.001), HbA1c (p < 0.001), total cholesterol (p < 0.001), LDL-cholesterol (p = 0.003), triglycerides (p = 0.017), IL-6 (p = 0.045) and a significant increase in serum irisin (p < 0.001) were observed compared to baseline. After 12 months of treatment no significant differences were found compared to the levels at 6 months. The change in irisin from baseline (Δ_irisin) was significantly related to the changes in total-cholesterol (Δ_total-cholesterol) (r = -0.293; p = 0.020), while the change in IL-6 (Δ_IL-6) was significantly related to the changes in WC (Δ_WC) (r = 0.347; p = 0.006). Conclusions Additive treatment with GLP1-analogues results in an increase in serum circulating irisin levels and a decrease in IL-6. The post-treatment change in irisin was correlated with a decrease in total cholesterol, while the change in IL-6 was correlated with a decrease in WC.
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GLP-1RAs elevate circulating irisin levels and BDNF.
“Additional evidence has indicated that GLP-1RAs elevated circulating irisin levels and BDNF (47, 48).”
From GLP-1 agonists and exercise: the future of lifestyle prioritization (2025) · cites this paper as [47]
Interleukin-6 and tumor necrosis factor-alpha are central to the inflammatory cascade and directly influence insulin resistance, endothelial cell activation, and plaque instability.
“Pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), are central to the inflammatory cascade, directly influencing insulin resistance, endothelial cell activation, and plaque instability (7, 8).”
Strong associations between subsequent reductions in body weight, HbA1c, and visceral fat and reductions in inflammatory biomarkers were found in several of the trials included in this evaluation.
“Strong associations between subsequent reductions in body weight, HbA1c, and visceral fat and reductions in inflammatory biomarkers were found in several of the trials included in our evaluation (7, 28, 35, 51, 52).”
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- Authors
- Guarnotta, V., Bianco, M. J., Vigneri, E., Panto’, F., Lo Sasso, B., Ciaccio, M., Pizzolanti, G., & Giordano, C.
- Affiliations
- University of Palermo (IT)
- Corresponding author
- Pizzolanti, Giuseppe
- Giordano, Carla
- Venue
- Nutrition, Metabolism and Cardiovascular Diseases
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 31
- Issue
- 11
- Pages
- 3193-3201
- ISSN
- 0939-4753 (ISSN-L)
- OpenAlex
- W3185983283
- Cited by
- 36
- References
- 48
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 11 · 2023: 5 · 2022: 1
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nutrition Metabolism and Cardiovascular Diseases (publishedVersion)
- PubMed (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- GLP-1 receptor agonists, dulaglutide, liraglutide, type 2 diabetes, irisin, interleukin-6, inflammatory cytokines, myokines, total cholesterol, waist circumference, glycemic control, insulin resistance
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Liraglutide, Glucagon-Like Peptide-1 Receptor Agonists, Aged, Blood Glucose, Cholesterol, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Glucagon-Like Peptides, Female, Fibronectins, Humans, Hypoglycemic Agents, Immunoglobulin Fc Fragments, Insulin, Male, Middle Aged, Recombinant Fusion Proteins, Time Factors, Biomarkers, Interleukin-6, Treatment Outcome, Inflammation Mediators, Incretins, Waist Circumference
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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