Ginkgo biloba extract (EGb 761) has been shown to ameliorate some defects associated with the insulin resistance syndrome and so patients with Type 2 diabetes mellitus (T2DM) may be inclined to co-ingest the herb with their medications, such as metformin. This study was designed to determine if the co-ingestion of EGb 761 and metformin would alter the pharmacokinetic properties of metformin in T2DM patients and persons without diabetes, who may ingest it for other purposes.Normal glucose tolerance (NGT) subjects (n=10; age, 39.2±14.0 years; fasting plasma glucose (FPG), 90±7mg/dl; body mass index (BMI), 24.1±3.7kg/m 2 ) and 10 T2DM patients (n=10; age, 51.7±8.9 years; FPG, 150±7mg/dl; BMI, 33.7±5.7kg/m 2 ) completed a randomized, double-blind, placebo-controlled crossover study. They ingested either EGb 761 (120mg/day as a single dose) or a vegetable-based placebo during each arm for 3 months. At the end of each arm, the NGT subject ingested a single 500mg dose of metformin (non-diabetics) and the T2DM subject took his/her prescribed metformin dose (250–850mg) with 120mg EGb 761. Blood and urine samples were collected over an 8-h period, and in the case of T2DM subjects, additionally over the first 2h of the subsequent 3 days.Ingestion of EGb 761 produced no significant changes in diagnostic laboratory tests in either group, except reducing glycosylated hemoglobin A 1c levels (from 7.7±1.2 to 7.2±0.9%, P<0.05) in T2DM the subjects. The pharmacokinetic parameters of metformin were all significantly different (P<0.05) between the NGT (500mg) and 8 out of 10 of the T2DM subjects who were prescribed 500mg of metformin during the placebo cycles. During the EGb 761 cycles, only the elimination half-life in the T2DM subjects was significantly increased (0.117±0.085 to 0.141±0.100, P<0.05).The co-ingestion of 120mg of EGb 761 and 500mg of metformin did not significantly affect the pharmacokinetic properties of metformin. Further studies are required to verify this observation for smaller and larger dose of metformin with other doses of EGb 761, since T2DM patients on medication constitute a very heterogeneous group.