Effects of gliclazide on platelet aggregation and the plasminogen activator inhibitor type 1 level in patients with type 2 diabetes mellitus.

Vascular complications are a common factor determining morbidity and mortality of diabetic patients. In vitro studies have revealed that gliclazide has antiplatelet activities. To clinically assess this action, we measured the effects of gliclazide on platelet activities and abnormal fibrinolysis in patients with type 2 diabetes mellitus. We studied 14 patients aged 38 to 72 years (9 men and 5 women) with type 2 diabetes mellitus who have been treated with glibenclamide in our hospital for more than 6 months. We switched from glibenclamide to gliclazide using the average ratio of the respective doses, 2.5 vs 40 mg. We titrated the dose of gliclazide to keep the glycemic control at the same level as the previous (glibenclamide) treatment. We measured 10 micromol/L serotonin-induced or 0.5 micromol/L adenosine diphosphate (ADP)-induced platelet aggregate formation by particle counting using light scattering at baseline and up to 6 months after the switch. After switching to gliclazide, platelet aggregate formation induced by serotonin was significantly reduced (P < .05, compared with the levels observed after glibenclamide treatment). The body mass index, fasting plasma glucose, immunoreactive insulin, homeostasis model assessment of insulin resistance, hemoglobin A(1c) (HbA(1c)), total cholesterol, triglycerides, high-density lipoprotein cholesterol, prothrombin time, activated partial thromboplastin time, fibrinogen, thrombin-antithrombin III complex, plasmin-alpha2-plasmin inhibitor complex, and plasma plasminogen activator inhibitor type 1 (PAI-1) were not changed. In the group with improved HbA(1c) (n = 5), ADP-induced platelet aggregate formation and plasma PAI-1 level were significantly reduced (P < .05, compared with the group with aggravated HbA(1c), n = 9). Multiple regression analysis showed that percentage change of ADP-induced platelet aggregate formation (standardized beta = 0.540, P < .05) was independently associated with percentage change of plasma PAI-1 level in addition to percentage change of HbA(1c) (standardized beta = 0.657, P < .05) (R = 0.939, P < .05) after switching to gliclazide. The other independent variants, like the final dose of gliclazide, homeostasis model assessment of insulin resistance, percentage change of prothrombin time, activated partial thromboplastin time, and total cholesterol, were not significantly associated with the percentage change of plasma PAI-1 level. These results indicate that gliclazide inhibits platelet aggregation via the serotonin pathway, independently of the metabolic control per se. Furthermore, in the patients with improved glycemic control, gliclazide could inhibit ADP-induced platelet aggregation and reduce PAI-I level. Taken together, the results show that gliclazide may be more useful for the prevention of diabetic vascular complications than glibenclamide.