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

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 ± 13y) 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.