Liraglutide reduces oxidative stress and restores heme oxygenase-1 and ghrelin levels in patients with type 2 diabetes: a prospective pilot study.
BACKGROUND
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).


METHODS
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.


METHODS
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.
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; Division of Endocrinology, Diabetes and Metabolism (M.R., A.A.R.), University of South Carolina School of Medicine, Columbia, South Carolina 29203; Division of Endocrinology (N.A., M.C.), The University of Texas Medical Branch, Galveston, Texas 77555; Department of Experimental Biomedicine and Clinical Neurosciences (A.M.G.), University of Palermo, Palermo 90127, Italy; Department of Drug Sciences (I.B.), University of Catania, Catania 90125, Italy; Laboratory for Molecular Genetics and Radiobiology (E.R.I.), Vinca Institute, University of Belgrade, Belgrade 11000, Serbia; Department of Hypertension (M.B.), Medical University of Lodz, Lodz 90-549, Poland; and Department of Biomedical and Biotechnological Sciences (G.L.V.), University of Catania, Catania 90125, Italy.
Manfredi
M
Rizzo
Nicola
N
Abate
Manisha
M
Chandalia
Ali A
AA
Rizvi
Rosaria V
RV
Giglio
Dragana
D
Nikolic
Antonella
A
Marino Gammazza
Ignazio
I
Barbagallo
Esma R
ER
Isenovic
Maciej
M
Banach
Giuseppe
G
Montalto
Giovanni
G
Li Volti
D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D054439:Ghrelin / Q000097:blood*; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051547:Heme Oxygenase-1 / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069450:Liraglutide; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010865:Pilot Projects; D011446:Prospective Studies
D054439:Ghrelin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D008687:Metformin; D051547:Heme Oxygenase-1