Effects of oral hypoglycaemic agents on platelet functions

Abstract The in vitro effects of three oral hypoglycaemic agents, gliclazide (1-(4-methylbenzen-sulfonyl)-3-[3-azabicylo(3,3,0)octyl]urea), glibenclamide (1-[4-[2-(chloro-2-methoxybenzamide)-ethyl]-phenyl-sulfonyl]-3-cyclohexyl-urea) and glimepiride (1-[4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-carboxamide)-ethyl]-phenylsulphonyl]3-(4-methylcyclohexyl)-urea), on functions of human platelets were evaluated. None of these agents up to a concentration of 40 μM inhibited platelet aggregation induced by thrombin. Glibenclamide and glimepiride in the range of 20–40μM suppressed Ca 2+ release from internal Ca 2+ stores induced by thrombin. Gliclazide showed no effect on arachidonic acid metabolism of human platelets. Glimepiride selectively inhibited the cyclooxygenase pathway, while the activities of 12-lipoxygenase and phospholipase A 2 were unaffected. Glibenclamide inhibited both the cyclooxygenase and 12-lipoxygenase pathways. It also attenuated arachidonic acid release from phospholipase A 2 . Oral hypoglycaemic agents with inhibitory effects on arachidonic acid metabolism may prove useful for the treatment of diabetic patients with enhanced platelet functions.