Liraglutide Reduces Oxidative Stress And Restores Heme Oxygenase-1 And Ghrelin Levels In Patients With Type 2 Diabetes: a prospective pilot study.

Abstract

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 impact of liraglutide on markers of oxidative stress, heme oxygenase-1 (HO-1), and plasma ghrelin levels in patients with type-2 diabetes (T2DM). Design and setting: A prospective pilot study of two months’ duration performed at the Unit of Diabetes and Cardiovascular Prevention at University of Palermo, Italy. Patients and Intervention(s): 20 subjects with T2DM (10 men and 10 women, mean age: 57±13 years) were treated with liraglutide subcutaneously (0.6mg/daily for 2 weeks, followed by 1.2mg/daily) in addition to metformin (1500 mg/daily 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. Results: The addition of liraglutide resulted in a significant decrease in glycated hemoglobin (HbA1c) (8.5±0.4 vs. 7.5±0.4%, p<0.0001). In addition, plasma ghrelin and glutathione (GSH) concentrations increased (8.2±4.1 vs. 13.6±7.3 pg/ml, p=0.0007 and 0.36±0.06 vs. 0.44±0.07 nmol/ml, p=0.0002, respectively), while serum lipid hydroperoxides and HO-1 decreased (0.11±0.05 vs. 0.04±0.07 pg/ml, p=0.0487 and 7.7±7.7 vs. 3.6±1.8 pg/ml, p=0.0445, 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 appeared to be independent of the known effects of liraglutide on glucose metabolism.