Intake of St John's wort improves the glucose tolerance in healthy subjects who ingest metformin compared with metformin alone

AimsOur objective was to investigate the steady-state pharmacokinetic and pharmacodynamic interaction between the antidepressive herbal medicine St John's wort and the antidiabetic drug metformin. MethodsWe performed an open cross-over study in 20 healthy male subjects, who received 1g of metformin twice daily for 1 week with and without 21 days of preceding and concomitant treatment with St John's wort. The pharmacokinetics of metformin was determined, and a 2h oral glucose tolerance test was performed. ResultsSt John's wort decreased the renal clearance of metformin but did not affect any other metformin pharmacokinetic parameter. The addition of St John's wort decreased the area under the glucose concentration-time curve [702 (95% confidence interval, 643-761) vs. 629min*mmol/L (95% confidence interval, 568-690), P = 0.003], and this effect was caused by a statistically significant increase in the acute insulin response. ConclusionsSt John's wort improves glucose tolerance by enhancing insulin secretion independently of insulin sensitivity in healthy male subjects taking metformin.