DIABETES/METABOLISM RESEARCH AND REVIEWS RESEARCH ARTICLE Diabetes Metab Res Rev 2008; 24: 231–237. Published online 30 October 2007 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/dmrr.794 Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects Gloria Formoso 1,2† Elena A. De Filippis 1† Noemi Michetti 1,2 Patrizia Di Fulvio 1,2 Assunta Pandolfi 2,3 Tonino Bucciarelli 2,4 Giovanni Ciabattoni 2,4 Antonio Nicolucci 5 Giovanni Dav` ı 1,2 Agostino Consoli 1,2 * 1 Department of Medicine and Aging Sciences, University -G. d’Annunzio, Chieti, Italy 2 Aging Research Center, Ce.S.I., -G. d’Annunzio- University Foundation, Chieti, Italy 3 Department of Biomedical Sciences, Chieti-Pescara, Italy 4 Department of Drug Sciences University -G. d’Annunzio, Chieti, Italy 5 Consorzio Mario Negri Sud – S. Maria Imbaro, Italy † These two authors contributed equally to the manuscript. *Correspondence to: Dr Agostino Consoli, Department of Medicine and Aging Sciences, Edificio CeSI, Room 271, University of Chieti, via dei Vestini, 1, 66100 Chieti, Italy. E-mail: consoli@unich.it Received: 27 June 2007 Revised: 13 September 2007 Accepted: 14 September 2007 Abstract Background In type 2 diabetes, metformin reduces cardiovascular risk beyond the effect of glycaemic control. Since oxidative stress and the consequent enhanced platelet activation contribute to accelerated atherosclerosis in diabetes, we hypothesized that metformin could reduce oxidative stress in this condition. Methods We randomized 26 newly diagnosed type 2 diabetic subjects to assume either metformin (M, n = 13) or gliclazide (G, n = 13) for 12 weeks. Drugs were titrated as needed to achieve good glycaemic control. Before and after treatment, we determined blood glucose, insulin, HbA 1c , vitamin A and E levels and 8-iso-PGF 2α and 11-dehydro-thromboxane B 2 urinary excretion, an in vivo oxidative stress and a thromboxane-dependent platelet activation marker, respectively. Results Notwithstanding a comparable improvement in metabolic control, 8-iso-PGF 2α (M from 708 ± 32 to 589 ± 45 pg/mg cr, p < 0.001; G from 646 ± 80 to 665 ± 79, pg/mg cr, p = ns) and 11-dehydro-thromboxane B 2 (M from 2190 ± 196 to 1753 ± 150 pg/mg cr, p < 0.05; G from 2048 ± 202 to 1923 ± 223, pg/mg cr, p = ns) urinary excretion decreased after metformin but not after gliclazide treatment. After metformin, vitamin A and E levels significantly increased while they remained unchanged after gliclazide. Conclusions These data suggest that metformin could improve oxidative stress, preserve antioxidant function and restrain platelet activation in type 2 diabetes. Copyright  2007 John Wiley & Sons, Ltd. Keywords metformin; type 2 diabetes; oxidative stress; isoprostanes; platelet activation Introduction Type 2 diabetes is associated with both microvascular complications as well as enhanced risk of cardiovascular disease (CVD) [1]. Improved metabolic control is definitely associated with a significant reduction in the risk of developing microvascular complications, but with only a modest and barely significant reduction in CVD risk [2]. As a matter of fact, several other fac- tors, in addition to hyperglycaemia per se concur in determining accelerated atherosclerosis in diabetic patients [3]. Thus, there is considerable evi- dence that hyperglycaemia results in increased generation of reactive oxygen species (ROS), leading to increased oxidative stress in several tissues. This, in Copyright  2007 John Wiley & Sons, Ltd.