HEMOBIOLOGICAL PROPERTIES OF GLICLAZIDE

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with an increased risk of macro- and microvascular degenerative complications. Gliclazide is a second generation sulfonylurea that is widely used in the treatment of type II diabetes mellitus. Its hypoglycemic activity is well documented. In addition to its metabolic effects, gliclazide has beneficial effects on the hemobiological abnormalities of NIDDM, T hese effects are mediated by-the azabicyclo-octyl ring grafted on to i ts aulfonylurea core. Numerous studies have demonstrated that gliclazi de reduces platelet hyperadhesion and platelet hyperaggregability. The se actions have been extensively confirmed in diabetic patients over p eriods of up to 3 years. With regard to platelet functions, several gr oups have demonstrated a significant reduction in serum and intraplate let beta thromboglobulin and thromboxane Bz. Tn animal models, in-vitr o and in-vivo gliclazide stimulates endothelial prostacyclin synthesis . The beneficial effects of the compound on thromboxane/prostacyclin b alance have been recently confirmed in type II diabetic patients after a 3-month treatment period. Concerning fibrinolysis, gliclazide resto res low plasminogen activity to normal in NIDDM patients previously tr eated with first-generation sulfonyl-ureas. Gliclazide increases fibri nolytic potential by increasing endothelial cell tissue plasminogen ac tivator and pre-kallikrein activity. More recent studies suggest that gliclazide may have effects on fibrin network structure, rendering the fibrin more amenable to fibrinolysis. Finally, it has been shown that gliclazide has a potent free-radical-scavenging activity in vitro. Th is property has been recently confirmed in vivo in type II diabetic pa tients and may suggest that platelet reactivity and oxidative stress a re related in these patients. It is worth noting that the hemobiologic al properties of gliclazide are largely independent of its hypoglycemi c activity. In addition, these properties are not shared with other fi rst or second generation sulfonylureas.