Liraglutide Reduces Oxidative Stress and Restores Heme Oxygenase-1 and Ghrelin Levels in Patients with Type 2 Diabetes: A Prospective Pilot Study
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CONTEXT: Liraglutide is a glucagon-like peptide-1 analog and glucose-lowering agent whose effects on cardiovascular risk markers have not been fully elucidated. OBJECTIVE: We evaluated the effect of liraglutide on markers of oxidative stress, heme oxygenase-1 (HO-1), and plasma ghrelin levels in patients with type-2 diabetes mellitus (T2DM). DESIGN AND SETTING: A prospective pilot study of 2 months' duration has been performed at the Unit of Diabetes and Cardiovascular Prevention at University of Palermo, Italy. Patients and Intervention(s): Twenty subjects with T2DM (10 men and 10 women; mean age: 57 ± 13 y) were treated with liraglutide sc (0.6 mg/d for 2 wk, followed by 1.2 mg/d) in addition to metformin (1500 mg/d orally) for 2 months. Patients with liver disorders or renal failure were excluded. MAIN OUTCOME MEASURE(S): Plasma ghrelin concentrations, oxidative stress markers, and heat-shock proteins, including HO-1 were assessed. RESULTS: The addition of liraglutide resulted in a significant decrease in glycated hemoglobin (HbA1c) (8.5 ± 0.4 vs 7.5 ± 0.4%, P < .0001). In addition, plasma ghrelin and glutathione concentrations increased (8.2 ± 4.1 vs 13.6 ± 7.3 pg/ml, P = .0007 and 0.36 ± 0.06 vs 0.44 ± 0.07 nmol/ml, P = .0002, respectively), whereas serum lipid hydroperoxides and HO-1 decreased (0.11 ± 0.05 vs 0.04 ± 0.07 pg/ml, P = .0487 and 7.7 ± 7.7 vs 3.6 ± 1.8 pg/ml, P = .0445, respectively). These changes were not correlated with changes in fasting glycemia or HbA1c. CONCLUSIONS: In a 2-months prospective pilot study, the addition of liraglutide to metformin resulted in improvement in oxidative stress as well as plasma ghrelin and HO-1 concentrations in patients with T2DM. These findings seemed to be independent of the known effects of liraglutide on glucose metabolism.
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Liraglutide treatment decreases oxidative stress independently of its impact on glucose metabolism.
“In 2015, Rizzo et al. evidenced that the liraglutide treatment decreased oxidative stress and it was independent of the impact of liraglutide on glucose metabolism [125].”
From The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome (2022) · cites this paper as [125]
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Self-citation
- Authors
- Rizzo, M., Abate, N., Chandalia, M., Rizvi, A. A., Giglio, R. V., Nikolic, D., Marino Gammazza, A., Barbagallo, I., Isenovic, E. R., Banach, M., Montalto, G., & Volti, G. L.
- Affiliations
- University of South Carolina (US)
- The University of Texas Medical Branch at Galveston (US)
- University of Palermo (IT)
- Biomedical Department of Internal Medicine and Medical Specialties (M.R., R.V.G., D.N., G.M.), University of Palermo, Palermo 90127, Italy
- Euro-Mediterranean Institute of Science and Technology (M.R., A.M.G., I.B., G.L.V.), Palermo 90139, Italy
- University of Catania (IT)
- Laboratory for Molecular Genetics and Radiobiology (E.R.I.), Vinca Institute, University of Belgrade, Belgrade 11000, Serbia
- Medical University of Lodz (PL)
- Corresponding author
- Rizvi, Ali A.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-02-01
- Volume
- 100
- Issue
- 2
- Pages
- 603-606
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC4318909
- OpenAlex
- W2132146653
- Cited by
- 113
- References
- 20
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 13 · 2023: 11 · 2022: 15 · 2021: 8 · 2020: 8 · 2019: 13 · 2018: 5 · 2017: 8 · 2016: 12 · 2015: 6
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- VinaR (Institute of Nuclear Sciences "Vinča") (submittedVersion, other-oa)
- Funders
- Bristol-Myers Squibb
- University of South Carolina
- National Institutes of Health (UL1TR000071)
- School of Medicine, University of South Carolina
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- liraglutide, type 2 diabetes, oxidative stress, heme oxygenase-1, ghrelin, glucagon-like peptide-1 analogues, metformin, glutathione, lipid hydroperoxides, HbA1c, heat shock proteins, cardiovascular risk markers, glycemic control, insulin resistance, dyslipidemia
- MeSH terms
- Liraglutide, Adult, Aged, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Female, Humans, Hypoglycemic Agents, Male, Metformin, Middle Aged, Pilot Projects, Prospective Studies, Oxidative Stress, Heme Oxygenase-1, Glucagon-Like Peptide 1, Ghrelin
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