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

AIMS: Our 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. METHODS: We performed an open cross-over study in 20 healthy male subjects, who received 1 g 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 2 h oral glucose tolerance test was performed. RESULTS: St 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. 629 min*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. CONCLUSIONS: St John's wort improves glucose tolerance by enhancing insulin secretion independently of insulin sensitivity in healthy male subjects taking metformin.