The comparison of effects of gliclazide, metformin and pioglitazone monotherapies on fibrinolysis, inflamation and endothelial functions in patients with type 2 diabetes mellitus

Diabetes mellitus is a chronic disease characterized by abnormalities in metabolisms of carbohydrate, lipid and protein. In diabetic patients, there is a markedly increased risk of cardiovascular disease. ß-cell dysfunction and insulin resistance play an important role in the pathogenesis of type 2 diabetes mellitus. Sulfonylureas are a group of drug that produced for ameliorate insulin secretion failure which was the result of ß-cell dysfunction. Two drug groups, biguanides and thiazolidinediones are targetting the insulin resistance. It has been shown that gliclazide, metformin and pioglitazone have lowering effects on cardiovascular risk factors as well as decreasing blood glucose . The aim of our study is to assess and compare the effects of gliclazide, metformin and pioglitazone monotherapies on fibrinolysis, inflamation and endothelial functions with their known effects on glycemic control in patients with type 2 diabetes mellitus. After screening period, 60 newly diagnosed type 2 diabetic patients were randomized into gliclazide (20 patients), metformin (20 patients) and pioglitazone (20 patients) groups. Height, weight and blood pressure of the patients were measured. Their BMI?s were calculated. Also anthropometric measures (waist circumference, hip circumference and body fat ratio) were taken. These measurements were repeated in 0, 3, 6 ve 12. months. Three patients (1 patient in gliclazide group, 1 patient in metformin group and 1 patient in pioglitazone group) were excluded because of being late to their engagements. After reached the optimal doses, 55 patient were followed 3 months, 47 patients for 6 months and 24 patient for 12 months. Any side effect was seen for the patients. At the first application and after 0, 3, 6 and 12. months fasting plasma glucose (FPG), postprandial plasma glucose (PPG), HbA1c, insulin, C-peptide, ALT, AST, BUN, creatinine, total cholesterol, LDL-C, HDL-C, triglyceride in blood samples microalbumine and creatinine in urine samples were measured. After reached the optimal doses in addition lipoprotein (a), TAFI, t-PA, PAI-1, fibrinogen vWF, IL-1, IL-6, TNF-?, hsCRP, ICAM-1, E-selectin and homocystein levels in 0, 3, 6 ve 12. months were also measured. In gliclazide group, no difference was seen on body weight. However, in metformin and pioglitazone groups, marked but not statistically significant decrease was seen on body weight. BMI in metformin group showed statistically significant decrease was found but in gliclazide and pioglitazone groups it did not. Statistically significant decrease were established for waist circumference in gliclazide group, for hip circumference in metformin group, both for waist and hip circumference in pioglitazon group. In metformin and pioglitazone groups, statistically significant decrease were found in serum levels of FPG, PPG and HbA1c. In gliclazide group only levels of FPG and HbA1c significantly decreased. HOMA score significantly decreased in gliclazide and pioglitazone groups, but no significant dicrease was found in metformin group. In gliclazid group total cholesterol and lipoprotein (a) levels were found to be significantly decreased. Serum level of HDL-C was found significantly increased and triglyceride level significantly decreased in pioglitazone group. No significant difference for lipid parameters was found in metformin group. Levels of vWF in pioglitazone group was found to be statistically significant decreased. No significant improvement was seen for levels of IL-1, IL-6 in gliclazide and metformin groups. In pioglitazone group marked but not significant decrease was seen on levels of TNF-?. In pioglitazon group levels of IL-6 was found statistical significant decreased. Levels of E-selectin in gliclazid group, levels of ICAM-1 in metformin group, both levels of ICAM-1 and E-selectine in pioglitozon group were found to be significantly dicreased. Homocystein levels was found to be dicreased significantly for all of the groups. In metformin group, a significant correlation between HbA1c and E-selectin was established. In pioglitazone group, a significant correlation was found between HbA1c and PAI-1. It was concluded that gliclazide, metformin and pioglitazone monotherapies may effect positively on nontraditional cardivascular risk factors as well as their useful glycemic effects in patients with type 2 diabetes mellitus and pioglitazone is more effective than gliclazid and metformin for these effects.