CLINICS 2012;67(7):711-717 CLINICAL SCIENCE DOI:10.6061/clinics/2012(07)03 Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus Helena Atroch Machado,I Marcelo Vieira,I Maria Rosaria Cunha,I Marcia Regina Soares Correia,I Rosa Tsunechiro Fukui,II Rosa Ferreira dos Santos,I Dalva Marreiro Rocha,I Bernardo Leo Wajchenberg,II Silvia G. Lage,II Maria Elizabeth Rossi da SilvaI I Hospital das Cl´ınicas da Faculdade de Medicina da Universidade de S a˜o Paulo, Laboratory of Medical Investigation (LIM-18), S a˜o Paulo/SP, Brazil. II Hospital das Cl´ınicas da Faculdade de Medicina da Universidade de S a˜o Paulo, Heart Institute (InCor) S a˜o Paulo/SP, Brazil. OBJECTIVE: To compare the effects of glimepiride and metformin on vascular reactivity, hemostatic factors and glucose and lipid profiles in patients with type 2 diabetes. METHODS: A prospective study was performed in 16 uncontrolled patients with diabetes previously treated with dietary intervention. The participants were randomized into metformin or glimepiride therapy groups. After four months, the patients were crossed over with no washout period to the alternative treatment for an additional four- month period on similar dosage schedules. The following variables were assessed before and after four months of each treatment: 1) fasting glycemia, insulin, catecholamines, lipid profiles and HbA1 levels; 2) t-PA and PAI-1 (antigen and activity), platelet aggregation and fibrinogen and plasminogen levels; and 3) the flow indices of the carotid and brachial arteries. In addition, at the end of each period, a 12-hour metabolic profile was obtained after fasting and every 2 hours thereafter. RESULTS: Both therapies resulted in similar decreases in fasting glucose, triglyceride and norepinephrine levels, and they increased the fibrinolytic factor plasminogen but decreased t-PA activity. Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow. Neither metformin nor glimepiride affected endothelial-dependent or endothelial-independent vasodilation of the brachial artery. CONCLUSIONS: Glimepiride and metformin were effective in improving glucose and lipid profiles and norepinephrine levels. Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels. As both therapies increased plasminogen levels but reduced t-PA activity, a coagulation process was likely still ongoing. KEYWORDS: Treatment; Metabolic profile; Vascular reactivity; Hemostatic factors; Type 2 diabetes. Machado HA, Vieira M, Cunha MR, Correia MRS, Fukui RT, Santos RF et al. Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus. Clinics. 2012;67(7):711-717. Received for publication on November 28, 2011; First review completed on December 28, 2011; Accepted for publication on March 5, 2012 E-mail: maria_cunha@uol.com.br Tel.: 55 11 3061 7259 INTRODUCTION Cardiovascular disease is the leading cause of mortality in patients with type 2 diabetes mellitus (DM2). The effective control of glycemia can delay but not prevent vascular complications, which are likely related to many other poorly controlled atherogenic factors, such as hyperlipidemia, Copyright 2012 CLINICS – This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non- commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. No potential conflict of interest was reported. hypertension, oxidative stress, accelerated aging, hyperin- sulinemia, disturbances in coagulation and fibrinolysis (1). Biguanides and sulfonylureas remain the principal oral therapeutic options for treating patients with DM2 (2). The biguanide metformin has been established as a first-line drug for the management of type 2 diabetes. Its indications are supported by its potency, lack of weight gain, low risk of hypoglycemia and mode of action in countering insulin resistance (3). The drug’s anti-atherosclerotic and cardio-protective effects appear to reflect a combination of glucose-independent effects on the vascular endothelium, suppressant effects on glycation, oxidative stress and the formation of adhesion molecules, and anti-inflammatory properties, in addition to stimulating fibrinolysis and favorable effects on lipid profiles (4). 711